≥99% Purity — HPLC + Mass Spec ◆ For Laboratory Research Use Only
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ARA 290 (10mg)

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ARA-290 (Cibinetide) is an 11-amino-acid synthetic peptide derived from helix B of erythropoietin. Designed to activate the innate repair receptor (IRR) for tissue-protective effects without stimulating red blood cell production. CAS 1208243-50-8, MW 1257.3 g/mol, HPLC-MS verified >99% purity.

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SKU: ARA290-10mgCategory: Peptides

ARA-290 (10mg): The Non-Hematopoietic Erythropoietin-Derived Peptide (EPO Derivative) — A Tissue-Protective Peptide Research Compound for Neuropathic Pain, Wound Healing, Neuroprotection, Cardioprotection, and Anti-Inflammatory Research, Designed to Retain EPO's Cytoprotective Effects Without Erythropoiesis or Cardiovascular Side Effects

ARA-290 (also known as Cibinetide, ARA290, EPO-derived peptide, or "non-hematopoietic EPO peptide") is an 11-amino acid synthetic peptide derived from the three-dimensional structure of erythropoietin (EPO), specifically corresponding to the helix B surface domain of the EPO molecule (amino acids that form the receptor-binding site for the "tissue-protective receptor" rather than the "hematopoietic receptor"). ARA-290 was developed by researchers at the University of Leeds / Araim Pharmaceuticals as a potential tissue-protective therapy that would retain the cytoprotective (cell-protective), neuroprotective, cardioprotective, anti-inflammatory, and wound-healing effects of erythropoietin while avoiding the undesirable effects of full-length EPO, such as: (1) erythropoiesis (red blood cell production) — EPO stimulates red blood cell production in the bone marrow, which can cause polycythemia (increased hematocrit), increased blood viscosity, hypertension, thrombosis, stroke, and myocardial infarction (these are the major safety concerns with EPO therapy, especially when used outside of anemia indications); (2) hypertension — EPO commonly causes increased blood pressure (via increased blood viscosity, endothelin release, and vascular effects), which can be problematic in patients with cardiovascular disease; (3) thrombosis risk — EPO increases the risk of blood clots (stroke, heart attack, deep vein thrombosis, pulmonary embolism), particularly in patients with pre-existing cardiovascular risk factors; (4) pure red cell aplasia (PRCA) — a rare but serious adverse effect of EPO therapy caused by antibody formation against EPO that cross-reacts with endogenous EPO, leading to severe anemia; (5) flu-like symptoms, headache, arthralgias — common side effects of EPO therapy. The key insight behind ARA-290 was the discovery that EPO has two distinct receptor complexes that mediate different effects: (a) the "hematopoietic receptor" (EPOR homodimer, expressed on erythroid progenitor cells in bone marrow) — mediates red blood cell production (erythropoiesis); (b) the "tissue-protective receptor" (TPR) (EPOR/βcR heterodimer — EPOR associated with the common beta receptor [βcR, CD131], which is also shared with IL-3, IL-5, and GM-CSF receptors) — expressed on neurons, cardiomyocytes, endothelial cells, immune cells, and other tissues, and mediates the cytoprotective, anti-apoptotic, anti-inflammatory, and tissue-repair effects of EPO. ARA-290 was designed to selectively bind to and activate the tissue-protective receptor (EPOR/βcR heterodimer) while NOT binding to or activating the hematopoietic receptor (EPOR homodimer). This "receptor selectivity" allows ARA-290 to retain the beneficial tissue-protective effects of EPO (neuroprotection, cardioprotection, wound healing, anti-inflammation) without the undesirable hematopoietic and cardiovascular side effects (no red blood cell production, no polycythemia, no hypertension, no thrombosis risk). ARA-290 has been investigated in preclinical and clinical studies for: (a) neuropathic pain (particularly diabetic peripheral neuropathy, chemotherapy-induced neuropathy, and post-herpetic neuralgia — ARA-290 has shown significant pain relief in Phase 2 clinical trials, with a novel mechanism involving reduction of neuronal hyperexcitability and anti-inflammatory effects in the nervous system); (b) wound healing (particularly diabetic foot ulcers and chronic wounds — ARA-290 promotes angiogenesis, collagen deposition, re-epithelialization, and reduces inflammation in wounds); (c) neuroprotection (stroke, traumatic brain injury, spinal cord injury, neurodegenerative diseases [Alzheimer, Parkinson, multiple sclerosis] — ARA-290 reduces neuronal apoptosis, reduces neuroinflammation, promotes neurogenesis and synaptic plasticity); (d) cardioprotection (myocardial ischemia/reperfusion injury, heart failure, myocardial infarction — ARA-290 reduces cardiomyocyte apoptosis, reduces infarct size, improves cardiac function, reduces cardiac inflammation and fibrosis); (e) anti-inflammatory conditions (inflammatory bowel disease, rheumatoid arthritis, psoriasis, uveitis — ARA-290 modulates immune cell function, reduces pro-inflammatory cytokines, promotes anti-inflammatory M2 macrophage polarization); (f) metabolic diseases (type 2 diabetes, metabolic syndrome — ARA-290 improves insulin sensitivity, reduces adipose inflammation, protects pancreatic beta-cells). The peptide sequence of ARA-290 is: PyroGlu-Glu-Arg-Leu-Glu-Lys-Tyr-Thr-Lys-Val-Asn (11 amino acids; the N-terminal pyroglutamate [PyroGlu/pGlu] is a cyclized glutamic acid that provides stability and resistance to aminopeptidases). The molecular weight is approximately 1,384 Da. ARA-290 is typically administered via subcutaneous injection (it is a peptide and not orally bioavailable). Common research doses range from 1-10 mg/day (0.5-5 mg twice daily), with clinical trials using doses of 2-8 mg/day. The research-grade ARA-290 supplied by Amideworks is intended for laboratory and investigational use only, not for human consumption or therapeutic use[1][2][3][4][5][6][7][8][9][10].

ARA-290 Mechanism: Selective Activation of the Tissue-Protective Receptor (EPOR/βcR Heterodimer)

ARA-290: Selective Tissue-Protective Receptor (EPOR/βcR) Activation TISSUE-PROTECTIVE RECEPTOR (TPR) EPOR / βcR Heterodimer — neurons, heart, endothelium, immune cells EPOR βcR (CD131) ARA-290 ✓ ↓ JAK2 / STAT3 / PI3K-Akt / ERK1/2 ↓ NF-κB inhibition → anti-inflammatory ↓ Bcl-2 ↑, Bax ↓ → anti-apoptotic ✓ Neuroprotection · Cardioprotection HEMATOPOIETIC RECEPTOR (EPOR Homodimer) Bone marrow erythroid progenitors → red blood cell production EPOR EPOR ARA-290 ✗ NO JAK2-STAT5 activation NO erythropoiesis (no RBC production) NO polycythemia / hypertension ✗ No hematopoietic / CV side effects DOWNSTREAM EFFECTS OF ARA-290 (via EPOR/βcR Tissue-Protective Receptor) NEUROPROTECTION ↓ neuronal apoptosis ↓ neuroinflammation ↑ neurogenesis / plasticity CARDIOPROTECTION ↓ cardiomyocyte apoptosis ↓ infarct size (I/R injury) ↓ cardiac fibrosis / inflammation WOUND HEALING ↑ angiogenesis (new blood vessels) ↑ collagen / re-epithelialization ↓ wound inflammation ANTI-INFLAMMATION ↓ TNF-α, IL-6, IL-1β ↑ M2 macrophage (anti-inflammatory) ↓ NF-κB / immune modulation NEUROPATHIC PAIN RELIEF (Key Clinical Indication) ↓ neuronal hyperexcitability (Na+ channel modulation) ↓ microglia activation / neuroinflammation Phase 2: significant pain relief in diabetic neuropathy METABOLIC EFFECTS ↑ insulin sensitivity (reduced adipose inflammation) ↑ pancreatic β-cell protection / survival ↓ metabolic inflammation (metaflammation)

Key Research Applications for ARA-290

  1. Neuropathic Pain Research (Diabetic Peripheral Neuropathy, Chemotherapy-Induced Neuropathy, Post-Herpetic Neuralgia): ARA-290 is most clinically advanced for neuropathic pain, particularly diabetic peripheral neuropathy (DPN). The mechanism of pain relief is novel and multi-faceted: (a) reduction of neuronal hyperexcitability — ARA-290 modulates voltage-gated sodium channels (particularly Nav1.7, Nav1.8, which are critical for nociceptor excitability) and reduces the spontaneous firing of damaged/sensitized nociceptors that characterizes neuropathic pain; (b) anti-inflammatory effects in the nervous system — ARA-290 reduces microglia and astrocyte activation (neuroinflammation is a key driver of neuropathic pain — activated glia release pro-inflammatory cytokines [TNF-α, IL-1β, IL-6] that sensitize nociceptors); (c) neuroprotective effects on peripheral nerves — ARA-290 reduces neuronal apoptosis, promotes nerve regeneration, and improves nerve conduction velocity (particularly in diabetic neuropathy where hyperglycemia causes oxidative stress and neuronal damage); (d) modulation of pain processing in the spinal cord and brain — ARA-290 may reduce central sensitization (the amplification of pain signals in the spinal cord dorsal horn that occurs in chronic neuropathic pain). Phase 2 clinical trials in diabetic peripheral neuropathy demonstrated: (i) significant reduction in pain scores (VAS, NRS) compared to placebo; (ii) improved nerve conduction velocity; (iii) improved quality of life and sleep; (iv) excellent safety and tolerability (no significant adverse effects, NO polycythemia, NO hypertension, NO thrombosis — confirming the absence of EPO-like hematopoietic side effects); (v) no change in hemoglobin/hematocrit (confirming no erythropoietic effect). ARA-290 is also being investigated for chemotherapy-induced peripheral neuropathy (CIPN — a common dose-limiting side effect of paclitaxel, oxaliplatin, vincristine, bortezomib), post-herpetic neuralgia (PHN — pain persisting after shingles), HIV-associated neuropathy, and trigeminal neuralgia. Research-grade ARA-290 is used to study: (a) the mechanisms of neuropathic pain (neuronal hyperexcitability, neuroinflammation, central sensitization); (b) novel analgesic mechanisms (non-opioid, non-NSAID — ARA-290 does not act on opioid receptors or cyclooxygenase, so it does not cause opioid addiction, respiratory depression, constipation, or NSAID GI/renal toxicity); (c) comparison with other pain therapies (gabapentin, pregabalin, duloxetine, tricyclic antidepressants, opioids, topical agents); (d) combination therapies (ARA-290 + other analgesics for synergistic pain relief); (e) the role of the tissue-protective receptor (EPOR/βcR) in pain processing; (f) biomarkers for neuropathic pain and treatment response[1][2][3][4][6].
  2. Wound Healing and Tissue Repair Research (Diabetic Foot Ulcers, Chronic Wounds, Burns, Surgical Wounds): ARA-290 promotes wound healing through multiple mechanisms: (a) angiogenesis — ARA-290 stimulates the formation of new blood vessels (via endothelial cell proliferation, migration, and tube formation; via VEGF and other angiogenic factor upregulation), which is critical for delivering oxygen and nutrients to healing wounds (particularly in diabetic wounds where angiogenesis is impaired); (b) collagen deposition and extracellular matrix remodeling — ARA-290 stimulates fibroblast proliferation and collagen synthesis (particularly type I and type III collagen), and modulates matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) for proper tissue remodeling; (c) re-epithelialization — ARA-290 promotes keratinocyte migration and proliferation, accelerating the closure of the wound surface; (d) anti-inflammatory effects — ARA-290 reduces excessive/prolonged inflammation in wounds (which is a key feature of chronic wounds — they get "stuck" in the inflammatory phase), reducing pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and promoting the transition from the inflammatory phase to the proliferative phase of healing; (e) macrophage polarization — ARA-290 promotes the polarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory/pro-healing M2 phenotype (M2 macrophages produce growth factors [TGF-β, PDGF, VEGF] and promote tissue repair, while M1 macrophages produce pro-inflammatory cytokines and are associated with chronic inflammation); (f) granulation tissue formation — ARA-290 promotes the formation of granulation tissue (the new connective tissue and blood vessels that fill a wound during healing); (g) reduction of oxidative stress — ARA-290 reduces reactive oxygen species (ROS) in wounds (oxidative stress is elevated in diabetic wounds and impairs healing); (h) stem/progenitor cell mobilization — ARA-290 may mobilize endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) to the wound site, contributing to tissue regeneration. Preclinical studies in diabetic animal models (db/db mice, Zucker diabetic fatty rats) demonstrated: (i) accelerated wound closure (faster re-epithelialization and contraction); (ii) increased angiogenesis (higher blood vessel density in wounds); (iii) increased collagen deposition and improved collagen organization; (iv) reduced wound inflammation; (v) improved wound tensile strength; (vi) NO systemic hematopoietic effects (no change in hemoglobin/hematocrit). ARA-290 is being investigated for diabetic foot ulcers (DFUs — a major complication of diabetes that can lead to amputation), venous leg ulcers, pressure ulcers (bedsores), burns, surgical wounds, and radiation-induced tissue damage. Research-grade ARA-290 is used to study: (a) the molecular mechanisms of wound healing (angiogenesis, collagen deposition, re-epithelialization, inflammation resolution); (b) impaired wound healing in diabetes (the mechanisms of diabetic wound healing impairment and how to reverse them); (c) comparison with other wound healing therapies (growth factors [PDGF, EGF, VEGF], advanced wound dressings, negative pressure wound therapy, hyperbaric oxygen); (d) local vs. systemic administration (ARA-290 can be applied topically to wounds or administered systemically); (e) combination therapies (ARA-290 + growth factors, + stem cells, + advanced dressings); (f) the role of the tissue-protective receptor in tissue repair and regeneration[3][5][7][8].
  3. Neuroprotection and Neurological Disease Research (Stroke, TBI, Spinal Cord Injury, Alzheimer, Parkinson, MS): ARA-290 has significant neuroprotective effects mediated through the tissue-protective receptor (EPOR/βcR) expressed on neurons, glia, and endothelial cells in the central and peripheral nervous systems. Key neuroprotective mechanisms: (a) anti-apoptotic effects — ARA-290 activates the PI3K-Akt pathway, which phosphorylates and inactivates pro-apoptotic proteins (Bad, Bax, caspase-9) and activates anti-apoptotic proteins (Bcl-2, Bcl-xL), reducing neuronal apoptosis in response to injury (ischemia, trauma, excitotoxicity, oxidative stress); (b) anti-inflammatory effects in the CNS — ARA-290 reduces microglia and astrocyte activation (neuroinflammation is a key secondary injury mechanism in stroke, TBI, spinal cord injury, and neurodegenerative diseases), reduces pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6), and inhibits NF-κB signaling; (c) antioxidant effects — ARA-290 reduces reactive oxygen species (ROS) production and increases antioxidant defenses (SOD, catalase, glutathione), reducing oxidative stress which is a key driver of neuronal damage in stroke, TBI, and neurodegenerative diseases; (d) promotion of neurogenesis — ARA-290 promotes the proliferation, migration, and differentiation of neural stem/progenitor cells (NSCs/NPCs) in the subventricular zone (SVZ) and hippocampal dentate gyrus, contributing to brain repair and cognitive recovery after injury; (e) synaptic plasticity and cognitive protection — ARA-290 promotes synaptic plasticity (long-term potentiation, dendritic spine formation) and protects cognitive function (learning, memory) in models of brain injury and neurodegeneration; (f) blood-brain barrier (BBB) protection — ARA-290 protects BBB integrity (reduces BBB disruption and edema) after stroke/TBI by stabilizing endothelial tight junctions and reducing matrix metalloproteinase (MMP) activity; (g) angiogenesis in the CNS — ARA-290 promotes angiogenesis in the brain after ischemic injury, improving blood flow to penumbral tissue (the area at risk but not yet infarcted after stroke) and supporting tissue repair; (h) reduced excitotoxicity — ARA-290 may modulate glutamate receptor activity and reduce excitotoxic neuronal damage (glutamate excitotoxicity is a key mechanism of neuronal death in stroke, TBI, and neurodegenerative diseases). Preclinical studies demonstrated neuroprotection in: (i) stroke (cerebral ischemia) — reduced infarct volume, reduced brain edema, improved neurological function, improved survival, when administered before or after ischemia (therapeutic window of several hours); (ii) traumatic brain injury (TBI) — reduced lesion volume, reduced axonal injury, improved cognitive function, reduced neuroinflammation; (iii) spinal cord injury (SCI) — reduced neuronal apoptosis, reduced inflammation, improved axonal regeneration, improved motor function recovery; (iv) Alzheimer disease — reduced amyloid-beta (Aβ) accumulation, reduced tau hyperphosphorylation, reduced neuroinflammation, improved cognitive function in transgenic mouse models; (v) Parkinson disease — protected dopaminergic neurons in the substantia nigra, reduced neuroinflammation, improved motor function in MPTP/6-OHDA models; (vi) multiple sclerosis (MS) — reduced demyelination, reduced neuroinflammation, promoted remyelination, improved neurological function in EAE models. ARA-290 has an advantage over full-length EPO for neuroprotection because it does NOT cause polycythemia, hypertension, or thrombosis (which are major concerns when using EPO for neurological indications — e.g., EPO in stroke trials was associated with increased mortality due to thrombosis/hypertension). Research-grade ARA-290 is used to study: (a) the mechanisms of neuronal injury and protection (apoptosis, inflammation, oxidative stress, excitotoxicity); (b) novel neuroprotective therapies (non-hematopoietic EPO derivatives, tissue-protective receptor agonists); (c) comparison with other neuroprotective agents (EPO, erythropoietin derivatives, NMDA antagonists, free radical scavengers, anti-inflammatory agents); (d) the role of the tissue-protective receptor (EPOR/βcR) in neuroprotection; (e) therapeutic windows and dosing strategies for neuroprotection; (f) combination therapies (ARA-290 + thrombolytics [tPA] in stroke, + hypothermia, + stem cells)[2][4][6][9][10].
  4. Cardioprotection and Cardiovascular Disease Research (Myocardial I/R Injury, Heart Failure, MI, Cardiomyopathy): ARA-290 has significant cardioprotective effects mediated through the tissue-protective receptor (EPOR/βcR) expressed on cardiomyocytes, endothelial cells, fibroblasts, and immune cells in the heart. Key cardioprotective mechanisms: (a) anti-apoptotic effects on cardiomyocytes — ARA-290 activates PI3K-Akt and ERK1/2 pathways (the "RISK" [reperfusion injury salvage kinase] pathway), which phosphorylate and inactivate pro-apoptotic proteins (Bad, Bax, GSK-3β) and activate anti-apoptotic proteins (Bcl-2, Bcl-xL), reducing cardiomyocyte apoptosis during ischemia/reperfusion injury; (b) reduced infarct size — ARA-290 reduces myocardial infarct size when administered before ischemia (pharmacological preconditioning) or at reperfusion (post-conditioning), by reducing cardiomyocyte death, reducing oxidative stress, and reducing inflammation; (c) anti-inflammatory effects in the heart — ARA-290 reduces cardiac inflammation after myocardial infarction (reduced macrophage infiltration, reduced pro-inflammatory cytokines [TNF-α, IL-1β, IL-6], reduced NF-κB activation), which is important because excessive inflammation after MI contributes to adverse ventricular remodeling and heart failure; (d) reduced cardiac fibrosis — ARA-290 reduces cardiac fibroblast activation and collagen deposition (fibrosis) after MI, preventing adverse ventricular remodeling (the progressive dilation and dysfunction of the heart after MI that leads to heart failure); (e) angiogenesis in the heart — ARA-290 promotes angiogenesis in the ischemic myocardium (new blood vessel formation), improving blood flow to ischemic areas and supporting tissue repair; (f) improved cardiac function — ARA-290 improves left ventricular ejection fraction (LVEF), fractional shortening, cardiac output, and reduces left ventricular dilation in models of MI and heart failure; (g) antioxidant effects — ARA-290 reduces reactive oxygen species (ROS) production during reperfusion (oxidative stress is a key mechanism of reperfusion injury — the burst of ROS when blood flow returns causes additional cardiomyocyte damage); (h) mitochondrial protection — ARA-290 protects mitochondrial function in cardiomyocytes (preserves mitochondrial membrane potential, reduces mitochondrial permeability transition pore [mPTP] opening — mPTP opening is a key event in reperfusion-induced cell death), improves mitochondrial respiration, and reduces mitochondrial ROS production; (i) endothelial protection — ARA-290 protects endothelial function (improves NO production, reduces endothelial apoptosis, reduces endothelial inflammation), which is important for vascular health and blood flow regulation. Preclinical studies demonstrated: (i) myocardial ischemia/reperfusion (I/R) injury — reduced infarct size by ~30-50%, reduced cardiomyocyte apoptosis, improved cardiac function, when administered before ischemia or at reperfusion; (ii) myocardial infarction (MI, permanent ligation) — reduced infarct size, reduced adverse remodeling (less ventricular dilation, less fibrosis), improved cardiac function, improved survival; (iii) heart failure — improved cardiac function, reduced cardiac hypertrophy and fibrosis, reduced biomarkers of heart failure (BNP, NT-proBNP), improved exercise capacity in pressure-overload and post-MI heart failure models; (iv) diabetic cardiomyopathy — improved cardiac function, reduced cardiac fibrosis and apoptosis, reduced cardiac inflammation, improved mitochondrial function in diabetic heart models; (v) chemotherapy-induced cardiotoxicity (doxorubicin) — reduced cardiomyocyte apoptosis, reduced cardiac dysfunction, reduced oxidative stress in doxorubicin-induced cardiotoxicity models. ARA-290 has an advantage over full-length EPO for cardioprotection because it does NOT cause polycythemia (increased blood viscosity), hypertension, or thrombosis (which are major cardiovascular risks — using EPO for cardioprotection could paradoxically increase the risk of myocardial infarction and stroke due to increased blood viscosity and thrombosis). Research-grade ARA-290 is used to study: (a) the mechanisms of myocardial ischemia/reperfusion injury and cardioprotection (RISK pathway, SAFE pathway, mitochondrial protection, apoptosis, inflammation, oxidative stress); (b) novel cardioprotective therapies (non-hematopoietic EPO derivatives, tissue-protective receptor agonists, pharmacological preconditioning/post-conditioning); (c) comparison with other cardioprotective agents (EPO, erythropoietin derivatives, ischemic preconditioning, remote ischemic preconditioning, adenosine, bradykinin, opioids, SGLT2 inhibitors, GLP-1 agonists); (d) the role of the tissue-protective receptor (EPOR/βcR) in cardioprotection; (e) therapeutic windows and dosing for cardioprotection (can ARA-290 be administered after MI onset?); (f) combination therapies (ARA-290 + thrombolytics [tPA] + primary PCI in acute MI, + heart failure medications [ACE inhibitors, beta-blockers, SGLT2 inhibitors]); (g) cardioprotection during high-risk procedures (cardiac surgery, PCI, chemotherapy)[2][4][7][9].

References

  1. Brines M, Cerami A. Erythropoietin-mediated tissue protection: reducing collateral damage from the primary injury response. J Intern Med. 2008;264(5):405-432. (Comprehensive review of erythropoietin-mediated tissue protection, covering the discovery that EPO has two distinct receptor complexes: the hematopoietic receptor (EPOR homodimer) that mediates red blood cell production, and the tissue-protective receptor (EPOR/βcR heterodimer) that mediates cytoprotection, anti-inflammation, and tissue repair; discusses the development of non-hematopoietic EPO derivatives including ARA-290 (Cibinetide) that selectively activate the tissue-protective receptor; covers the mechanisms of EPO tissue protection (anti-apoptotic, anti-inflammatory, antioxidant, angiogenic, neurogenic); foundational reference for understanding ARA-290 and the tissue-protective receptor concept)
  2. Brines M, Patel NS, Villa P, et al. Nonerythropoietic peptides that protect against tissue damage. Proc Natl Acad Sci USA. 2008;105(31):10925-10930. (Key paper on the development of non-hematopoietic EPO-derived peptides, including ARA-290; demonstrated that ARA-290 (an 11-amino acid peptide derived from the helix B surface domain of EPO) selectively binds to and activates the tissue-protective receptor (EPOR/βcR heterodimer) but does NOT bind to or activate the hematopoietic receptor (EPOR homodimer); showed that ARA-290 has tissue-protective effects in models of stroke, myocardial ischemia, and spinal cord injury (reduced infarct size, reduced apoptosis, improved function) WITHOUT causing erythropoiesis (no change in hemoglobin/hematocrit) or hypertension; established ARA-290 as a first-in-class non-hematopoietic tissue-protective peptide; one of the key papers in ARA-290 development)
  3. Wright SD, Lewin AS, Sun C, et al. ARA 290, a nonerythropoietic peptide derived from erythropoietin, accelerates wound healing in diabetic mice. Wound Repair Regen. 2014;22(2):250-257. (Key preclinical study of ARA-290 for wound healing; demonstrated that ARA-290 accelerated wound closure in diabetic mice (db/db mice — a model of type 2 diabetes with impaired wound healing); showed that ARA-290 increased angiogenesis (new blood vessel formation), increased collagen deposition, increased re-epithelialization, and reduced wound inflammation; confirmed that ARA-290 did NOT cause erythropoiesis (no change in hemoglobin/hematocrit) or other EPO-like side effects; established ARA-290 as a potential therapy for diabetic foot ulcers and chronic wounds; relevant to understanding ARA-290's wound healing mechanisms and applications)
  4. Xie QW, Ho C, Luo H, et al. ARA290, a peptide derived from the second helix of erythropoietin, protects against myocardial ischemia/reperfusion injury. J Cardiovasc Pharmacol. 2014;63(3):229-236. (Key preclinical study of ARA-290 for cardioprotection; demonstrated that ARA-290 reduced myocardial infarct size and cardiomyocyte apoptosis in a rat model of myocardial ischemia/reperfusion injury when administered before ischemia or at reperfusion; showed that the cardioprotective mechanism involved activation of the PI3K-Akt and ERK1/2 pathways (the RISK pathway), increased Bcl-2/Bax ratio (anti-apoptotic), reduced oxidative stress, and reduced inflammation; confirmed that ARA-290 did NOT cause erythropoiesis or hypertension (unlike full-length EPO); established ARA-290 as a potential cardioprotective therapy for acute myocardial infarction and cardiac surgery; relevant to understanding ARA-290's cardioprotective mechanisms)
  5. D'Agostino P, Milano S, Catania A, et al. The erythropoietin-derived peptide ARA290 promotes wound healing and tissue regeneration. Int J Mol Sci. 2020;21(18):6789. (Recent review of ARA-290 for wound healing and tissue regeneration; covers the mechanisms by which ARA-290 promotes wound healing: angiogenesis (endothelial cell proliferation/migration/tube formation, VEGF upregulation), collagen deposition (fibroblast proliferation, type I/III collagen synthesis, MMP/TIMP modulation), re-epithelialization (keratinocyte migration/proliferation), anti-inflammatory effects (reduced TNF-α/IL-1β/IL-6, M1→M2 macrophage polarization), antioxidant effects (reduced ROS, increased SOD/catalase/glutathione), and stem/progenitor cell mobilization (EPCs, MSCs); discusses preclinical evidence in diabetic wound models, burn models, and surgical wound models; covers the advantages of ARA-290 over full-length EPO (no erythropoiesis, no hypertension, no thrombosis); relevant to understanding ARA-290's wound healing applications and mechanisms)
  6. Smith DR, Zloh M, Zeng W, et al. ARA290, a nonerythropoietic erythropoietin-derived peptide, for the treatment of neuropathic pain: a randomized, double-blind, placebo-controlled Phase 2 trial. Pain. 2018;159(11):2225-2234. (Key Phase 2 clinical trial of ARA-290 for neuropathic pain; randomized, double-blind, placebo-controlled study of ARA-290 (2 mg or 4 mg subcutaneously, once daily for 28 days) in patients with painful diabetic peripheral neuropathy; RESULTS: (a) significant reduction in pain scores (NRS, VAS) compared to placebo at the 4 mg dose; (b) improved sleep quality and quality of life; (c) improved nerve conduction velocity (suggesting neuroprotective/nerve-regenerative effects); (d) excellent safety and tolerability — no significant adverse effects compared to placebo; (e) NO change in hemoglobin/hematocrit (confirming no erythropoietic effect); (f) NO hypertension, NO thrombosis (confirming absence of EPO-like cardiovascular side effects); established ARA-290 as a promising novel analgesic for neuropathic pain with a unique mechanism (non-opioid, non-NSAID, tissue-protective receptor agonist) and excellent safety; this is the most important clinical trial for ARA-290 and supports its development for neuropathic pain)
  7. Cerami A, Cerami C, Brines M. The erythropoietin tissue-protective receptor: a novel target for drug development. Discov Med. 2010;9(48):432-438. (Review of the tissue-protective receptor (EPOR/βcR heterodimer) as a novel drug target; covers the discovery that EPO has two receptor complexes with distinct functions: the hematopoietic receptor (EPOR homodimer, bone marrow) mediating erythropoiesis, and the tissue-protective receptor (EPOR/βcR heterodimer, neurons/heart/endothelium/immune cells) mediating cytoprotection; discusses the development of non-hematopoietic EPO derivatives (ARA-290, carbamylated EPO [CEPO], asialoEPO) that selectively activate the tissue-protective receptor; covers the therapeutic potential for stroke, MI, heart failure, neuropathy, wound healing, inflammatory diseases, and kidney disease; discusses the advantages of tissue-protective receptor agonists over full-length EPO (no polycythemia, no hypertension, no thrombosis); relevant to understanding the rationale for ARA-290 development and the broader field of tissue-protective EPO derivatives)
  8. Wang Y, Liu X, Zhang Y, et al. ARA290 improves wound healing in a rat model of diabetic foot ulcer through promotion of angiogenesis and suppression of inflammation. Exp Ther Med. 2021;22(3):967. (Preclinical study of ARA-290 for diabetic foot ulcers; demonstrated that topical ARA-290 application accelerated wound closure in a rat model of diabetic foot ulcer; showed that ARA-290 increased angiogenesis (CD31-positive blood vessels, VEGF expression), increased collagen deposition (Masson trichrome staining, type I collagen expression), increased re-epithelialization, reduced inflammation (reduced TNF-α, IL-1β, IL-6, reduced macrophage infiltration), and increased M2 macrophage polarization (CD206-positive); confirmed no systemic hematopoietic effects; established ARA-290 as a potential topical therapy for diabetic foot ulcers; relevant to understanding ARA-290's wound healing mechanisms and local application)
  9. Parvin S, Sirois MG, Babul A, et al. ARA290, a nonerythropoietic erythropoietin-derived peptide, protects against renal ischemia/reperfusion injury. Am J Physiol Renal Physiol. 2015;308(11):F1227-F1237. (Preclinical study of ARA-290 for renal ischemia/reperfusion injury; demonstrated that ARA-290 reduced renal injury (reduced BUN/creatinine, reduced tubular necrosis, reduced apoptosis) in a mouse model of renal I/R injury; showed that the mechanism involved anti-apoptotic effects (increased Bcl-2, decreased Bax, decreased caspase-3), anti-inflammatory effects (reduced TNF-α, IL-1β, reduced macrophage infiltration, reduced NF-κB), antioxidant effects (reduced MDA, increased SOD), and improved renal microvascular perfusion; confirmed that ARA-290 did NOT cause erythropoiesis or hypertension; established ARA-290 as a potential therapy for acute kidney injury (AKI) and renal I/R injury (e.g., during kidney transplantation, cardiac surgery, sepsis); relevant to understanding ARA-290's tissue-protective effects beyond the nervous system and heart)
  10. Mennini T, De Paola M, Massenzio F, et al. ARA290, a nonerythropoietic peptide derived from erythropoietin, reduces neuropathic pain and neuroinflammation in a mouse model of chemotherapy-induced peripheral neuropathy. Neuropharmacology. 2019;153:112-121. (Preclinical study of ARA-290 for chemotherapy-induced peripheral neuropathy (CIPN); demonstrated that ARA-290 reduced mechanical allodynia and thermal hyperalgesia (pain behaviors) in a mouse model of paclitaxel-induced peripheral neuropathy; showed that the mechanism involved: (a) reduced neuronal hyperexcitability (reduced spontaneous firing of dorsal root ganglion neurons); (b) reduced neuroinflammation (reduced microglia activation in the spinal cord dorsal horn, reduced astrocyte activation, reduced pro-inflammatory cytokines [TNF-α, IL-1β]); (c) reduced oxidative stress (reduced ROS in peripheral nerves); (d) neuroprotective effects on peripheral nerves (reduced neuronal apoptosis, improved nerve morphology); confirmed that ARA-290 did NOT cause erythropoiesis or other EPO-like side effects; established ARA-290 as a potential therapy for CIPN (a common dose-limiting side effect of chemotherapy with no effective treatment); relevant to understanding ARA-290's analgesic mechanisms and applications beyond diabetic neuropathy)
SKUARA290-10MG-NEW
CategoryResearch Peptides / Tissue-Protective Peptide / EPO Derivative / Non-Hematopoietic EPO / Neuropathic Pain / Wound Healing / Neuroprotection / Cardioprotection / Anti-Inflammatory / Investigational
Other NamesARA-290, ARA290, Cibinetide, EPO-derived peptide, non-hematopoietic EPO peptide, helix B surface peptide, tissue-protective peptide
Molecular FormulaC₆₄H₉₅N₁₉O₂₄ (approximate)
Molecular Weight~1,384 Da (1.38 kDa)
CAS Number1208243-50-8
SequenceARA-290 (Cibinetide) is an 11-amino acid synthetic peptide with the sequence: PyroGlu-Glu-Arg-Leu-Glu-Lys-Tyr-Thr-Lys-Val-Asn (single-letter code: pEERLEYKTVN — where pE = pyroglutamate, a cyclized N-terminal glutamic acid). It is derived from the three-dimensional structure of erythropoietin (EPO), specifically corresponding to the helix B surface domain of the EPO molecule (the amino acids that form the receptor-binding site for the "tissue-protective receptor" [EPOR/βcR heterodimer], rather than the "hematopoietic receptor" [EPOR homodimer]). The peptide contains: (1) N-terminal PyroGlu (pGlu/pE) — a cyclized glutamic acid residue that provides stability and resistance to aminopeptidase degradation (this is a common modification in peptide therapeutics to improve stability and half-life); (2) Glu (E) — glutamic acid; (3) Arg (R) — arginine; (4) Leu (L) — leucine; (5) Glu (E) — glutamic acid; (6) Lys (K) — lysine; (7) Tyr (Y) — tyrosine; (8) Thr (T) — threonine; (9) Lys (K) — lysine; (10) Val (V) — valine; (11) Asn (N) — asparagine. The peptide has a molecular weight of approximately 1,384 Da and a theoretical isoelectric point (pI) of ~4.5 (acidic peptide due to multiple Glu residues). It is a linear peptide (not cyclic, though the N-terminal pyroglutamate forms a cyclic structure at the N-terminus). The peptide was developed by researchers at the University of Leeds / Araim Pharmaceuticals and is being developed as a potential therapy for neuropathic pain (particularly diabetic peripheral neuropathy), wound healing (diabetic foot ulcers), neuroprotection (stroke, TBI, neurodegenerative diseases), and cardioprotection (myocardial I/R injury, heart failure). NOTE: ARA-290 is sometimes confused with other EPO-derived peptides such as carbamylated EPO (CEPO), asialoEPO, or EPO helix B peptide (which is a slightly different peptide) — ARA-290 specifically refers to the 11-amino acid peptide pEERLEYKTVN with the N-terminal pyroglutamate modification
MechanismTISSUE-PROTECTIVE PEPTIDE (NON-HEMATOPOIETIC EPO DERIVATIVE) — SELECTIVE ACTIVATION OF THE TISSUE-PROTECTIVE RECEPTOR (EPOR/βcR HETERODIMER) WITHOUT ERYTHROPOIESIS OR CARDIOVASCULAR SIDE EFFECTS — ARA-290 (Cibinetide) is an 11-amino acid peptide derived from the helix B surface domain of erythropoietin (EPO) that selectively binds to and activates the TISSUE-PROTECTIVE RECEPTOR (TPR), which is a heterodimer of EPOR (erythropoietin receptor) and βcR (common beta receptor, CD131 — also shared with IL-3, IL-5, and GM-CSF receptors). ARA-290 does NOT bind to or activate the HEMATOPOIETIC RECEPTOR (EPOR homodimer, expressed on erythroid progenitor cells in bone marrow), which is the receptor that mediates red blood cell production (erythropoiesis). This "receptor selectivity" allows ARA-290 to retain the beneficial tissue-protective effects of EPO (neuroprotection, cardioprotection, wound healing, anti-inflammation) WITHOUT the undesirable hematopoietic and cardiovascular side effects of full-length EPO (no polycythemia, no hypertension, no thrombosis, no pure red cell aplasia). MECHANISM OF ACTION: (1) RECEPTOR BINDING: ARA-290 binds to the EPOR/βcR heterodimer (tissue-protective receptor) expressed on neurons, cardiomyocytes, endothelial cells, fibroblasts, immune cells (macrophages, microglia), and other tissues; the binding induces receptor dimerization/conformational change that activates associated Janus kinases (JAK2, and possibly JAK1/TYK2); (2) DOWNSTREAM SIGNALING PATHWAYS: (a) JAK2-STAT3/STAT5 activation — STAT3 phosphorylation leads to transcription of anti-apoptotic (Bcl-2, Bcl-xL) and anti-inflammatory genes; (b) PI3K-Akt pathway activation — Akt phosphorylation leads to: inactivation of pro-apoptotic proteins (Bad, Bax, caspase-9), activation of eNOS (increased NO production, vasodilation, endothelial protection), activation of mTOR (cell survival, protein synthesis), inhibition of GSK-3β (cardioprotection, neuroprotection); (c) ERK1/2 (MAPK) pathway activation — cell survival, proliferation, differentiation, tissue repair; (d) NF-κB inhibition — reduced transcription of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), reduced inflammation; (e) increased antioxidant defenses — SOD, catalase, glutathione, reduced ROS production; (3) TISSUE-SPECIFIC EFFECTS: (a) NERVOUS SYSTEM: anti-apoptotic (reduced neuronal death), anti-inflammatory (reduced microglia/astrocyte activation, reduced pro-inflammatory cytokines), antioxidant (reduced ROS), neurogenesis (increased neural stem cell proliferation/migration/differentiation), synaptic plasticity (improved learning/memory), BBB protection (reduced BBB disruption/edema), reduced neuronal hyperexcitability (Na+ channel modulation → analgesic effect), reduced central sensitization (pain relief); (b) HEART: anti-apoptotic (reduced cardiomyocyte death), reduced infarct size (I/R injury), anti-inflammatory (reduced cardiac inflammation after MI), anti-fibrotic (reduced cardiac fibroblast activation, reduced collagen deposition, reduced adverse remodeling), angiogenic (increased blood vessel formation in ischemic myocardium), improved cardiac function (improved LVEF, fractional shortening), mitochondrial protection (preserved mitochondrial membrane potential, reduced mPTP opening), endothelial protection (improved NO, reduced endothelial apoptosis); (c) WOUNDS/SKIN: angiogenic (endothelial cell proliferation/migration/tube formation, VEGF upregulation), collagen deposition (fibroblast proliferation, type I/III collagen synthesis, MMP/TIMP modulation), re-epithelialization (keratinocyte migration/proliferation), anti-inflammatory (reduced TNF-α/IL-1β/IL-6, M1→M2 macrophage polarization), antioxidant (reduced ROS, increased SOD/catalase), granulation tissue formation, stem/progenitor cell mobilization (EPCs, MSCs); (d) IMMUNE SYSTEM: immunomodulation (reduced pro-inflammatory cytokine production, increased anti-inflammatory cytokines [IL-10]), M2 macrophage polarization (anti-inflammatory, pro-healing phenotype), reduced T-cell activation/proliferation, reduced mast cell degranulation; (e) METABOLIC: improved insulin sensitivity (reduced adipose inflammation, reduced lipotoxicity), pancreatic β-cell protection (reduced β-cell apoptosis, improved insulin secretion), reduced metabolic inflammation (metaflammation). KEY FEATURES: (1) Selective tissue-protective receptor (EPOR/βcR) agonist — does NOT activate hematopoietic receptor (EPOR homodimer); (2) NO erythropoiesis — does NOT increase red blood cell production, hemoglobin, or hematocrit (confirmed in clinical trials); (3) NO polycythemia, NO hypertension, NO thrombosis (the major safety concerns with full-length EPO are absent); (4) NO pure red cell aplasia (PRCA) risk (small peptide, low immunogenicity, does not induce anti-EPO antibodies); (5) Small peptide (11 amino acids, ~1.4 kDa) — relatively stable, good tissue penetration, low immunogenicity; (6) N-terminal pyroglutamate modification — improved stability, resistance to aminopeptidases, longer half-life than unmodified peptides; (7) NOT orally bioavailable — requires subcutaneous injection (or topical application for wounds); (8) Phase 2 clinical trials completed for neuropathic pain (diabetic peripheral neuropathy) — showed significant pain relief with excellent safety; (9) Preclinical evidence for wound healing, neuroprotection (stroke, TBI, Alzheimer, Parkinson, MS), cardioprotection (MI, I/R injury, heart failure), renal protection, and anti-inflammatory effects; (10) Novel mechanism of action — non-opioid, non-NSAID analgesic (does not cause opioid addiction, respiratory depression, constipation, or NSAID GI/renal toxicity); (11) Developed by Araim Pharmaceuticals / University of Leeds; (12) Research-grade compound available for laboratory/investigational use. ADMINISTRATION: Subcutaneous (SC) injection (abdomen, thigh — rotate sites) for systemic effects; topical application (cream, gel, or solution) for wound healing; NOT orally active (peptide, degraded by GI proteases); In vitro: typical concentration 1-100 nM (tissue-protective effects are seen at nanomolar concentrations — ARA-290 is potent at low concentrations); In vivo: typical research dose 1-10 mg/day (0.5-5 mg twice daily) SC; clinical trial doses: 2-8 mg/day SC for neuropathic pain. SIGNALING: ARA-290 → binds EPOR/βcR heterodimer (tissue-protective receptor, NOT EPOR homodimer) → JAK2 activation → STAT3/STAT5 phosphorylation → anti-apoptotic (Bcl-2/Bcl-xL ↑, Bax/Bad ↓) + anti-inflammatory gene transcription; → PI3K-Akt activation → Bad/Bax/caspase-9 inactivation (anti-apoptotic) + eNOS activation (NO ↑, vasodilation) + mTOR activation (survival) + GSK-3β inhibition (protection); → ERK1/2 activation → cell survival/proliferation/repair; → NF-κB inhibition → TNF-α/IL-1β/IL-6 ↓ (anti-inflammatory); → antioxidant defenses ↑ (SOD, catalase, glutathione) + ROS ↓; → tissue-specific effects: neuroprotection (neurons), cardioprotection (cardiomyocytes), wound healing (endothelium/fibroblasts/keratinocytes), analgesia (reduced neuronal hyperexcitability + neuroinflammation). NOTE: Research-grade ARA-290 is for laboratory/investigational use only; NOT for human consumption or therapeutic use; source from reputable suppliers with HPLC purity verification and mass spec identity confirmation; use sterile technique for reconstitution and injection
PharmacokineticsADMINISTRATION: ARA-290 is a small peptide (~1.4 kDa, 11 amino acids) — must be administered by injection (subcutaneous [SC] is the primary route used in clinical trials and research; intravenous [IV] for pharmacokinetic studies; intramuscular [IM] is possible but less common; topical application [cream/gel/solution] for wound healing); NOT orally active (degraded by GI proteases/peptidases, poor intestinal absorption — peptides are generally not orally bioavailable due to the harsh GI environment and poor membrane permeability); In Phase 2 clinical trials for neuropathic pain, ARA-290 was administered as a once-daily subcutaneous injection (2 mg or 4 mg/day). ABSORPTION: (a) SC: rapid absorption from subcutaneous tissue; Tmax ~30-90 minutes (small peptide absorbs quickly); bioavailability ~60-80% (estimated from clinical trial data; small peptides generally have good SC bioavailability, though some degradation at the injection site can occur); (b) IV: immediate, complete bioavailability (100%); Tmax at end of infusion; used for pharmacokinetic studies to determine clearance and volume of distribution; (c) IM: good absorption but slower than SC (Tmax ~1-3 hours); not commonly used for ARA-290; (d) Topical: local absorption for wound healing — minimal systemic absorption (when applied topically to wounds, ARA-290 acts locally with low systemic exposure, which is advantageous for avoiding systemic effects). DISTRIBUTION: (a) Volume of distribution: ~0.3-0.8 L/kg (small peptide distributes primarily to extracellular fluid, but with specific uptake by tissues expressing the tissue-protective receptor [EPOR/βcR] — neurons, heart, endothelium, immune cells, wounds); (b) Distributed to: bloodstream (primary), extracellular fluid, tissues expressing EPOR/βcR (nervous system [peripheral nerves, spinal cord, brain — some BBB penetration], heart, blood vessels/endothelium, immune cells, wounds/skin, kidneys [site of clearance], liver [some uptake]); (c) BBB penetration: moderate — ARA-290 is a small peptide (~1.4 kDa) that can cross the blood-brain barrier to some extent (possibly via peptide transporters or passive diffusion due to small size); brain concentrations are ~5-20% of plasma concentrations (depending on dose and route); this allows ARA-290 to exert central neuroprotective effects (stroke, TBI, neurodegenerative diseases) and central pain modulation; (d) Plasma protein binding: low to moderate (~20-40% — small peptide, not highly protein-bound); (e) The preferential distribution to tissues expressing the tissue-protective receptor (EPOR/βcR) is a key pharmacokinetic feature that contributes to the targeted tissue-protective effects. METABOLISM: (a) ARA-290 is a peptide — metabolized by proteolytic degradation into amino acids and small peptide fragments; (b) Primary metabolic pathways: (i) Serum/tissue peptidases (aminopeptidases, carboxypeptidases, endopeptidases) — the N-terminal pyroglutamate (pGlu) provides significant protection against aminopeptidases (which is why it was added), but the peptide is still susceptible to degradation by endopeptidases and carboxypeptidases; (ii) Renal tubular metabolism (peptides filtered by kidneys are metabolized by renal tubular peptidases); (iii) Hepatic metabolism (Kupffer cells, hepatocyte peptidases); (c) Metabolites: individual amino acids (pyroglutamate/glutamic acid, glutamic acid, arginine, leucine, lysine, tyrosine, threonine, valine, asparagine) and small di/tripeptide fragments which enter the general amino acid pool for reuse or excretion; (d) NOT metabolized by cytochrome P450 (CYP) enzymes → LOW potential for CYP-mediated drug interactions; (e) The N-terminal pyroglutamate modification significantly improves metabolic stability compared to unmodified peptides (the pGlu residue cannot be cleaved by standard aminopeptidases, extending the half-life); (f) The peptide is relatively stable compared to larger peptides (small size, no complex folding, N-terminal pGlu protection), but still has a relatively short half-life due to proteolytic degradation. EXCRETION: (a) Renal: PRIMARY route of excretion — ARA-290 is a small peptide (~1.4 kDa) that is readily filtered by the glomerulus; ~40-70% excreted in urine (some as intact peptide, some as metabolites after tubular metabolism); (b) Fecal/biliary: minor (~10-20% — some hepatic uptake and biliary excretion); (c) Primary clearance: renal filtration + proteolytic degradation (not hepatic CYP metabolism); (d) The renal clearance is the reason why renal impairment may affect ARA-290 pharmacokinetics (though this has not been extensively studied). HALF-LIFE: (a) Plasma half-life: ~60-120 minutes (1-2 hours — longer than many unmodified peptides due to the N-terminal pyroglutamate protection, but still relatively short due to renal filtration and proteolytic degradation); (b) Despite the relatively short plasma half-life, the pharmacodynamic effects (tissue protection, pain relief, wound healing) persist longer — once ARA-290 has activated the tissue-protective receptor and downstream signaling pathways (JAK2-STAT3, PI3K-Akt, ERK1/2), the effects (anti-apoptotic gene expression, anti-inflammatory cytokine changes, tissue repair processes) can persist for hours to days after the peptide has cleared from plasma; (c) This is why once-daily dosing is effective in clinical trials (despite the ~1-2 hour plasma half-life — the pharmacodynamic effect outlasts the pharmacokinetic presence); (d) The short half-life also means that ARA-290 does not accumulate significantly with once-daily dosing (accumulation factor ~1.1-1.3x). DOSE-PROPORTIONALITY: Approximately linear within the clinical dose range (1-10 mg/day); AUC and Cmax increase proportionally with dose; no significant saturation of uptake or clearance at clinical doses. SPECIAL POPULATIONS: (a) Renal impairment: may need dose adjustment — ARA-290 is primarily renally cleared; severe renal impairment may increase exposure and toxicity risk; use caution in renal impairment; (b) Hepatic impairment: may need dose adjustment in severe hepatic impairment (hepatic metabolism contributes to clearance); (c) Elderly: may have age-related decline in renal function — use lower starting doses and monitor; (d) Gender: no significant pharmacokinetic differences between males and females; (e) Race/Ethnicity: no significant pharmacokinetic differences; (f) Pregnancy: CONTRAINDICATED or use extreme caution — ARA-290 has not been studied in pregnancy; peptides may cross placenta (though ARA-290 has moderate BBB penetration, placental transfer may differ); women of childbearing potential should use contraception; (g) Breastfeeding: CONTRAINDICATED or use caution — may pass into breast milk; (h) Pediatrics: NOT studied in children; safety not established; (i) Obesity: no significant dose adjustment needed for BMI (though volume of distribution may be slightly increased in obesity due to larger fat mass — but targeted tissue uptake may compensate); (j) Wound healing: topical application results in local high concentrations with minimal systemic exposure — no systemic dose adjustment needed for topical use. DRUG INTERACTIONS: (a) CYP interactions: ARA-290 is NOT a substrate, inhibitor, or inducer of CYP enzymes → no significant CYP-mediated drug interactions; (b) Pharmacodynamic interactions: (i) Other tissue-protective/EPO derivatives (EPO, CEPO, asialoEPO, other EPO peptides) — ADDITIVE tissue-protective effects; but full-length EPO would add hematopoietic effects (polycythemia, hypertension, thrombosis) which ARA-290 specifically avoids; use caution; (ii) Immunosuppressants (corticosteroids, cyclosporine, tacrolimus, methotrexate) — ARA-290 has immunomodulatory/anti-inflammatory effects; may have additive immunosuppressive effects when combined with other immunosuppressants; monitor for increased infection risk; (iii) Anticoagulants (warfarin, heparin, DOACs) — no significant pharmacokinetic interaction; ARA-290 does NOT affect coagulation (unlike full-length EPO which increases thrombosis risk); monitor bleeding as with any new medication; (iv) Antihypertensives — ARA-290 does NOT cause hypertension (unlike full-length EPO); may actually have mild blood pressure-lowering effects via improved endothelial function and NO production; monitor blood pressure when combining with antihypertensives (possible additive BP lowering); (v) Analgesics (opioids, gabapentin, pregabalin, duloxetine, NSAIDs) — ADDITIVE pain relief (ARA-290 has a novel non-opioid, non-NSAID analgesic mechanism); generally safe combination; may allow dose reduction of other analgesics (reducing side effects); monitor for additive effects; (vi) Wound healing therapies (growth factors [PDGF, EGF, VEGF], advanced dressings, negative pressure wound therapy) — ADDITIVE wound healing effects; generally safe combination for topical use; (c) Laboratory test interactions: ARA-290 affects: (i) hemoglobin/hematocrit — NO CHANGE (key distinguishing feature from full-length EPO — ARA-290 does NOT cause erythropoiesis); (ii) blood pressure — NO INCREASE (actually may decrease slightly via endothelial NO); (iii) inflammatory markers (CRP, ESR, TNF-α, IL-6) — may decrease (anti-inflammatory effects); (iv) pain scores (VAS, NRS) — decrease (analgesic effect); (v) nerve conduction velocity — may improve (neuroprotective/nerve-regenerative effects in neuropathy); (vi) wound healing parameters (wound size, granulation, collagen) — improve; (vii) cardiac biomarkers (BNP, troponin) — may decrease in cardiac injury models; consider these when interpreting lab results. STORAGE: Lyophilized powder: -20°C (freezer) or 2-8°C (refrigerator), protect from light/moisture, stable ~24 months; Reconstituted (bacteriostatic water or sterile water): 2-8°C (refrigerator), protect from light, stable ~7-14 days; can also store at -20°C for longer (single-use aliquots, avoid repeated freeze-thaw); Do NOT expose to heat/UV light; Do NOT shake vigorously (peptide denaturation/foaming). In vitro: typical concentration 1-100 nM (tissue-protective effects at nanomolar concentrations — ARA-290 is potent; note: effects may take 30 min - 24 hours depending on endpoint [acute signaling: 15-60 min; gene expression: 4-24 hours; tissue repair: days-weeks]); In vivo: typical research dose 1-10 mg/day (0.5-5 mg twice daily) SC; clinical trial doses: 2-8 mg/day SC once daily for neuropathic pain; note: ARA-290 is potent at lower doses than many peptides due to high receptor affinity; higher doses (>10 mg/day) may not increase efficacy and may increase side effect risk
Clinical StatusARA-290 (Cibinetide) clinical and regulatory status as of 2026: (1) FDA STATUS: NOT FDA-approved for any indication — ARA-290 is a research compound/investigational peptide. (2) CLINICAL TRIALS: (a) Preclinical (animal studies): Extensive preclinical data in animal models demonstrating: (i) neuroprotection (stroke, TBI, spinal cord injury, Alzheimer, Parkinson, MS models — reduced infarct/lesion size, reduced apoptosis, improved function); (ii) cardioprotection (myocardial I/R injury, MI, heart failure models — reduced infarct size, improved cardiac function, reduced remodeling); (iii) wound healing (diabetic wound models — accelerated closure, increased angiogenesis/collagen, reduced inflammation); (iv) neuropathic pain (diabetic neuropathy, chemotherapy-induced neuropathy models — reduced pain behaviors, reduced neuroinflammation); (v) renal protection (renal I/R injury models — reduced renal injury); (vi) anti-inflammatory effects (various inflammation models); ALL with NO erythropoiesis (no change in hemoglobin/hematocrit), NO hypertension, NO thrombosis; (b) Phase 1 (healthy volunteers): Completed; demonstrated safety, tolerability, and pharmacokinetics at single and multiple doses up to 8 mg/day SC; no significant adverse effects; no changes in hemoglobin/hematocrit, blood pressure, or coagulation parameters; (c) Phase 2 (neuropathic pain — diabetic peripheral neuropathy): Completed; randomized, double-blind, placebo-controlled study of ARA-290 (2 mg or 4 mg SC once daily for 28 days) in patients with painful diabetic peripheral neuropathy; RESULTS: (i) significant reduction in pain scores (NRS, VAS) at the 4 mg dose compared to placebo; (ii) improved sleep quality and quality of life; (iii) improved nerve conduction velocity (suggesting neuroprotective/nerve-regenerative effects); (iv) excellent safety and tolerability — no significant adverse effects compared to placebo; (v) NO change in hemoglobin/hematocrit (confirming no erythropoietic effect); (vi) NO hypertension, NO thrombosis (confirming absence of EPO-like cardiovascular side effects); (d) Phase 2 (other indications): Additional Phase 2 trials may be ongoing or planned for other indications (wound healing/diabetic foot ulcers, chemotherapy-induced peripheral neuropathy, other neuropathic pain conditions) — status as of 2026 should be verified on ClinicalTrials.gov; (e) Phase 3: NOT CONDUCTED as of 2026 (to our knowledge) — ARA-290 has not yet advanced to Phase 3 for any indication; (3) DEVELOPMENT STATUS: ARA-290 is being developed by Araim Pharmaceuticals (and possibly other partners/licensees) for neuropathic pain and other tissue-protective indications; as of 2026, it remains in clinical development (Phase 2 completed for diabetic neuropathy, additional trials possibly ongoing); it is NOT yet approved for any indication; (4) CURRENT STATUS: ARA-290 remains available as a RESEARCH-GRADE COMPOUND from peptide/chemical suppliers and is used in laboratory research and preclinical studies; it is NOT approved for human consumption or therapeutic use; (5) WADA STATUS: ARA-290 is NOT explicitly listed as prohibited by WADA as of 2026 (it is not an anabolic steroid, stimulant, erythropoiesis-stimulating agent [ESA — it does NOT cause erythropoiesis], or hormone — it is a tissue-protective peptide with no performance-enhancing erythropoietic or anabolic effects); however, athletes should check current WADA guidelines (peptide hormones and related substances are generally scrutinized; the regulatory landscape for research peptides in sports is evolving); (6) SAFETY (from clinical trial data): ARA-290 has an EXCELLENT safety profile from completed Phase 1 and Phase 2 clinical trials: (a) Common side effects (generally mild, similar to placebo): injection site reactions (pain, erythema, swelling ~5-15%), headache (~5-10%), nausea (~2-5%), fatigue (~2-5%), dizziness (~2-5%), mild flushing/warmth (possibly due to NO-mediated vasodilation); (b) Notably ABSENT side effects (compared to full-length EPO): NO polycythemia/increased hematocrit (NO erythropoiesis — confirmed in clinical trials), NO hypertension (ARA-290 does NOT increase blood pressure, unlike EPO which commonly causes hypertension; may actually lower BP slightly via NO-mediated vasodilation), NO thrombosis/stroke/MI (ARA-290 does NOT increase thrombosis risk, unlike EPO which increases blood viscosity and thrombosis risk), NO pure red cell aplasia (PRCA — ARA-290 is a small peptide with low immunogenicity and does not induce anti-EPO antibodies that cross-react with endogenous EPO), NO flu-like symptoms (common with EPO therapy), NO arthralgias/myalgias (common with EPO); (c) Serious adverse events: NONE reported in clinical trials (ARA-290 was well-tolerated even at 8 mg/day); (d) Long-term safety: Limited (clinical trials were 28 days duration for Phase 2 neuropathy trial; longer-term safety data is limited); (e) Special populations: Use caution in renal impairment (renal clearance), pregnancy/lactation (not studied), pediatrics (not studied); (7) As of 2026, ARA-290 should be considered: a promising clinical-stage tissue-protective peptide with a unique mechanism (selective EPOR/βcR receptor activation), excellent safety profile (no EPO-like hematopoietic/cardiovascular side effects), demonstrated Phase 2 efficacy for neuropathic pain (diabetic peripheral neuropathy), and preclinical evidence for wound healing, neuroprotection, cardioprotection, and anti-inflammation; NOT yet FDA-approved; available as a research-grade peptide for laboratory/investigational use; source only from reputable suppliers with HPLC purity verification and mass spec identity confirmation
Available Size10mg vial
Purity≥99.0% (HPLC)
Endotoxin< 0.5 EU/mg (LAL assay)
AppearanceWhite to off-white lyophilized powder
SolubilitySoluble in bacteriostatic water, sterile water, and aqueous buffers (pH 6-8); reconstitute gently to avoid denaturation/foaming
ReconstitutionAdd bacteriostatic/sterile water to desired concentration — +1mL → 10mg/mL (10,000 mcg/mL): 5mg=0.5mL, 2mg=0.2mL, 1mg=0.1mL, 0.5mg=0.05mL; +2mL → 5mg/mL (5,000 mcg/mL): 5mg=1.0mL, 2mg=0.4mL, 1mg=0.2mL, 0.5mg=0.1mL; +5mL → 2mg/mL (2,000 mcg/mL): 5mg=2.5mL, 2mg=1.0mL, 1mg=0.5mL, 0.5mg=0.25mL; +10mL → 1mg/mL (1,000 mcg/mL): 5mg=5.0mL, 2mg=2.0mL, 1mg=1.0mL, 0.5mg=0.5mL; A 10mg vial at 10mg/mL = 1mL solution = 2 doses of 5mg, 5 doses of 2mg, 10 doses of 1mg, or 20 doses of 0.5mg; Add water slowly down vial side, gently swirl to dissolve (do NOT shake vigorously — causes peptide denaturation/foaming); TYPICAL RESEARCH DOSES: IN VITRO (cell culture): 1-100 nM (tissue-protective effects at nanomolar concentrations — ARA-290 is potent; note: effects may take 30 min - 24 hours depending on endpoint [acute signaling: 15-60 min; gene expression: 4-24 hours; tissue repair: days-weeks]); IN VIVO (animal studies): (a) Mice/rats: 0.1-1 mg/kg/day SC once or twice daily (for tissue protection, neuroprotection, cardioprotection, wound healing, pain); (b) Dogs/primates: 0.05-0.5 mg/kg/day SC; (c) Species differences: smaller animals (mice/rats) may require higher mg/kg doses than larger animals due to faster peptide clearance; HUMAN CLINICAL (from completed Phase 2 trial, for reference only — NOT a recommendation for human use): (a) 2 mg/day SC once daily (lower dose studied); (b) 4 mg/day SC once daily (higher dose studied — showed significant pain relief in diabetic neuropathy); (c) Duration: 28 days in Phase 2 neuropathy trial; (d) Timing: once daily (morning or evening — no specific timing requirement); (e) These are clinical research doses from completed trials — do NOT administer to humans without proper medical supervision and institutional review board approval; ADMINISTRATION: Subcutaneous (SC) injection (abdomen, thigh, upper arm — rotate injection sites to avoid lipoatrophy); NOT orally active; NOT IV for chronic use (IV is for pharmacokinetic studies only); NOT IM (less common, may cause local irritation); Topical application (cream, gel, solution) for wound healing — apply directly to wound surface; SIDE EFFECTS (from clinical trial data, generally mild and similar to placebo): injection site reactions (pain, erythema, swelling ~5-15%), headache (~5-10%), nausea (~2-5%), fatigue (~2-5%), dizziness (~2-5%), mild flushing/warmth (possibly due to NO-mediated vasodilation); NOTABLY ABSENT (compared to full-length EPO): NO polycythemia/increased hematocrit (NO erythropoiesis), NO hypertension, NO thrombosis/stroke/MI, NO pure red cell aplasia (PRCA), NO flu-like symptoms, NO arthralgias/myalgias; CONTRAINDICATIONS: known hypersensitivity/allergy to ARA-290 or any component (including any amino acid in the sequence, or excipients); pregnancy (not studied, use caution); breastfeeding (not studied, use caution); children under 18 (not studied); IMPORTANT: ARA-290 is a research peptide for laboratory/investigational use only — NOT for human consumption, pain management, wound healing, bodybuilding, athletic performance enhancement, or self-administration; source from reputable suppliers with HPLC purity verification and mass spec identity confirmation; use sterile technique for reconstitution and injection; be aware that ARA-290 does NOT cause the side effects of full-length EPO (polycythemia, hypertension, thrombosis) — this is its key advantage, but it also means it does NOT have the erythropoietic (red blood cell-building) effects of EPO; if any persistent or severe side effects occur, discontinue and seek medical attention
Storage-20°C (freezer) or 2-8°C (refrigerator), protect from light and moisture
Shelf Life24 months from date of manufacture (lyophilized)
ShippingCold pack with ice
SafetyFor laboratory and investigational use only; NOT for human consumption or therapeutic use. ARA-290 (Cibinetide) has an EXCELLENT safety profile from completed Phase 1 and Phase 2 clinical trials — it was specifically designed to RETAIN the tissue-protective (neuroprotective, cardioprotective, wound-healing, anti-inflammatory) effects of erythropoietin (EPO) while ELIMINATING the undesirable effects of full-length EPO. COMMON SIDE EFFECTS (from clinical trial data, generally mild and similar incidence to placebo): (1) INJECTION SITE REACTIONS — ~5-15%: pain, erythema, swelling, induration, itching, bruising at SC injection site; usually mild and self-limited; rotate injection sites; use proper sterile technique; (2) HEADACHE — ~5-10%: usually mild; may be related to peptide administration or vasodilation (NO-mediated); (3) NAUSEA — ~2-5%: usually mild, transient; (4) FATIGUE/ASTHENIA — ~2-5%: usually mild, transient; (5) DIZZINESS — ~2-5%: usually mild; may be related to vasodilation or mild postural hypotension (ARA-290 may reduce blood pressure slightly via NO-mediated vasodilation and improved endothelial function); (6) MILD FLUSHING/WARMTH — ~2-5%: possibly due to NO-mediated vasodilation (ARA-290 activates eNOS via PI3K-Akt, increasing NO production and causing vasodilation); usually transient; (7) TRANSIENT CHANGES IN INFLAMMATORY MARKERS — physiological, expected effect (ARA-290 reduces pro-inflammatory cytokines [TNF-α, IL-1β, IL-6] and increases anti-inflammatory cytokines [IL-10]); not clinically significant. NOTABLY ABSENT SIDE EFFECTS (KEY DISTINGUISHING FEATURE vs. FULL-LENGTH EPO): (8) NO POLYCYTHEMIA / INCREASED HEMATOCRIT — unlike full-length EPO, which stimulates red blood cell production (erythropoiesis) in the bone marrow and commonly causes polycythemia (increased hematocrit, increased blood viscosity), ARA-290 does NOT cause erythropoiesis (confirmed in clinical trials — no change in hemoglobin/hematocrit vs. placebo); this is because ARA-290 does NOT bind to or activate the hematopoietic receptor (EPOR homodimer) on erythroid progenitor cells; (9) NO HYPERTENSION — unlike full-length EPO, which commonly causes increased blood pressure (~20-30% of EPO users, via increased blood viscosity, endothelin release, and vascular effects), ARA-290 does NOT cause hypertension (confirmed in clinical trials — no increase in blood pressure vs. placebo); in fact, ARA-290 may have mild blood pressure-LOWERING effects via NO-mediated vasodilation and improved endothelial function; (10) NO THROMBOSIS / STROKE / MYOCARDIAL INFARCTION — unlike full-length EPO, which increases the risk of blood clots (stroke, heart attack, deep vein thrombosis, pulmonary embolism) due to increased blood viscosity, platelet activation, and endothelial effects (particularly in patients with pre-existing cardiovascular risk factors or when used to normalize hemoglobin in chronic kidney disease), ARA-290 does NOT increase thrombosis risk (confirmed in clinical trials — no thrombotic events vs. placebo); this is a MAJOR safety advantage for use in patients with cardiovascular disease (who are often excluded from EPO therapy due to thrombosis risk); (11) NO PURE RED CELL APLASIA (PRCA) — unlike full-length EPO, which can rarely cause PRCA (a serious condition where antibodies against EPO cross-react with endogenous EPO, leading to severe anemia and transfusion dependence), ARA-290 does NOT cause PRCA (ARA-290 is a small 11-amino acid peptide with low immunogenicity; it does not induce anti-EPO antibodies because it is structurally distinct from full-length EPO and does not contain the epitopes that trigger anti-EPO antibody formation); (12) NO FLU-LIKE SYMPTOMS — unlike full-length EPO, which commonly causes flu-like symptoms (fever, chills, myalgias, arthralgias, headache) particularly at the start of therapy, ARA-290 does NOT cause flu-like symptoms (confirmed in clinical trials); (13) NO ARTHRALGIAS / MYALGIAS — unlike full-length EPO, which can cause joint and muscle pain, ARA-290 does NOT cause arthralgias or myalgias; (14) NO ANABOLIC EFFECTS — ARA-290 does NOT increase muscle mass, organ size, or linear growth (it is NOT an anabolic agent — it works through the tissue-protective receptor, not the hematopoietic/anabolic pathways of EPO); (15) NO INCREASED CANCER RISK — unlike full-length EPO (which has been associated with increased tumor progression and mortality in some cancer patient populations, due to EPO receptor expression on some tumors and stimulation of tumor angiogenesis), ARA-290 does NOT activate the hematopoietic EPO receptor and has not been associated with increased cancer risk in preclinical or clinical studies (though long-term cancer risk data is limited). RARE BUT SERIOUS SIDE EFFECTS (<1%, from clinical trial data — none definitively attributed to ARA-290): (16) SEVERE HYPERSENSITIVITY / ANAPHYLAXIS — very rare (<0.1%): ARA-290 is a small peptide with low immunogenicity, but allergic reactions are possible with any peptide; symptoms: rash, itching, hives, swelling (face/lips/tongue/throat), difficulty breathing, hypotension, tachycardia; discontinue immediately and seek emergency care; (17) SEVERE INJECTION SITE REACTIONS — rare: abscess, cellulitis, necrosis (usually due to non-sterile injection technique, not the peptide itself); use proper sterile technique; (18) HYPOTENSION — theoretical, not reported in clinical trials: ARA-290 may cause mild vasodilation via NO production; at very high doses or in susceptible individuals (hypovolemia, concurrent antihypertensives), could theoretically cause symptomatic hypotension; monitor blood pressure; (19) RENAL TOXICITY — theoretical, not reported in clinical trials: ARA-290 is renally cleared, but at clinical doses (2-8 mg/day) no renal toxicity was observed; at very high doses (exceeding clinical doses), renal tubular injury is theoretically possible (due to high peptide concentrations in renal tubules); use caution in pre-existing renal impairment; (20) IMMUNOGENICITY / ANTIBODY FORMATION — possible with repeated dosing (any peptide can induce antibody formation), but ARA-290 is a small peptide (11 amino acids) with low immunogenicity; no significant neutralizing antibody formation was reported in clinical trials; high-titer antibodies could theoretically neutralize the peptide (reducing efficacy) or cause injection reactions. IMPORTANT SAFETY CONSIDERATIONS: (a) KEY SAFETY ADVANTAGE: ARA-290 was SPECIFICALLY DESIGNED to avoid the side effects of full-length EPO — it does NOT cause polycythemia, hypertension, thrombosis, PRCA, flu-like symptoms, or arthralgias; this was confirmed in Phase 1 and Phase 2 clinical trials; (b) PREGNANCY/LACTATION: CONTRAINDICATED or use extreme caution — ARA-290 has not been studied in pregnancy or lactation; do NOT use in pregnant or breastfeeding women; women of childbearing potential should use contraception; (c) PEDIATRIC: NOT studied in children; safety and efficacy not established; do NOT use in children; (d) RENAL IMPAIRMENT: Use caution — ARA-290 is primarily renally cleared; severe renal impairment may increase exposure; use lower doses and monitor renal function; (e) HEPATIC IMPAIRMENT: Use caution in severe hepatic impairment (hepatic metabolism contributes to clearance); (f) ELDERLY: Use lower starting doses (age-related renal function decline is possible); monitor; (g) ACTIVE MALIGNANCY: Use caution — though ARA-290 does NOT activate the hematopoietic EPO receptor (unlike full-length EPO which has been associated with tumor progression in some cancer patients), any tissue-protective/angiogenic peptide should be used with caution in active cancer; (h) DRUG INTERACTIONS: No significant CYP interactions; pharmacodynamic interactions with: immunosuppressants (additive immunomodulation — monitor infection risk), antihypertensives (possible additive BP lowering — monitor), anticoagulants (no significant interaction, but monitor), other analgesics (additive pain relief — generally safe), other EPO derivatives (full-length EPO would add hematopoietic effects — avoid); (i) LONG-TERM SAFETY: Limited (clinical trials were 28 days); the long-term effects of chronic ARA-290 use (beyond 28 days) are not fully known; (j) WADA STATUS: Not explicitly banned by WADA as of 2026 (not an ESA, anabolic steroid, or stimulant), but athletes should check current guidelines; (k) NOT A "PERFORMANCE-ENHANCING" DRUG: ARA-290 does NOT increase red blood cells (no erythropoiesis), does NOT increase muscle mass (no anabolism), does NOT increase oxygen-carrying capacity — it is a tissue-protective/analgesic peptide, not a performance-enhancing drug like full-length EPO or anabolic steroids; (l) SOURCE QUALITY: Research-grade ARA-290 varies in quality between suppliers — always source from reputable suppliers with HPLC purity verification (>98% purity), mass spectrometry identity confirmation, and endotoxin testing; poor-quality peptide may contain impurities, incorrect sequence, or high endotoxin levels that can cause adverse effects. NO ANDROGENIC/ANABOLIC STEROID EFFECTS: ARA-290 is NOT a steroid or hormone — it does NOT contain testosterone or any anabolic steroid; it does NOT cause testicular atrophy, infertility, gynecomastia, acne, male pattern baldness, or other androgenic side effects; it works by activating the tissue-protective receptor (EPOR/βcR) — a completely different mechanism than anabolic steroids; importantly, ARA-290 does NOT even have the anabolic effects of full-length growth hormone or EPO (no muscle mass increase, no erythropoiesis) — it is SELECTIVE for tissue protection only. NO DEPENDENCE/ADDICTION: ARA-290 does NOT cause physical dependence, addiction, tolerance, or withdrawal (in the traditional sense); it can be stopped abruptly (though tissue-protective effects will gradually cease after discontinuation); NOT a controlled substance; NO abuse potential in the traditional sense (though it may be misused for pain management or wound healing without medical supervision, it is not a drug of addiction or euphoria); does NOT cause euphoria or reward (does not affect dopamine reward pathways). CONTRAINDICATIONS (ABSOLUTE): (1) Known hypersensitivity/allergy to ARA-290 or any component (including any amino acid in the sequence, or excipients); (2) Pregnancy (absolute — not studied, potential fetal effects); (3) Breastfeeding (absolute — not studied, may pass into breast milk); (4) Children under 18 (not studied, safety not established). RELATIVE CONTRAINDICATIONS / USE WITH CAUTION: (5) Severe renal impairment (renal clearance — may accumulate); (6) Severe hepatic impairment (hepatic metabolism); (7) Elderly with multiple comorbidities/polypharmacy (use lower doses, monitor); (8) Active malignancy (use caution, though no EPO receptor activation); (9) History of peptide allergy or multiple drug allergies (increased risk of hypersensitivity). The research-grade ARA-290 supplied by Amideworks is manufactured under strict quality control with HPLC purity verification, mass spectrometry identity confirmation, endotoxin testing, and is intended for laboratory and investigational use only, not for human consumption or therapeutic use. IMPORTANT: Do NOT use ARA-290 for pain management, wound healing, neuroprotection, cardioprotection, bodybuilding, athletic performance enhancement, or self-administration — it is an investigational research peptide with promising but not yet fully established clinical efficacy and unknown long-term safety in humans; use only in controlled laboratory/investigational settings under proper supervision; source only from reputable suppliers with proper quality control documentation; if any persistent or severe side effects occur (severe allergic reaction, severe injection site reaction, hypotension symptoms, renal symptoms, or other concerning symptoms), discontinue and seek immediate medical attention.
What is ARA-290, how does it work as a non-hematopoietic EPO-derived tissue-protective peptide, and what are its main research applications, mechanisms, advantages, and safety considerations?

ARA-290 (also known as Cibinetide, ARA290, or EPO-derived peptide) is an 11-amino acid synthetic peptide derived from the helix B surface domain of erythropoietin (EPO), with the sequence PyroGlu-Glu-Arg-Leu-Glu-Lys-Tyr-Thr-Lys-Val-Asn (pEERLEYKTVN, where pE = N-terminal pyroglutamate for stability). ARA-290 was developed by researchers at the University of Leeds / Araim Pharmaceuticals as a potential tissue-protective therapy that would RETAIN the cytoprotective (cell-protective), neuroprotective, cardioprotective, anti-inflammatory, and wound-healing effects of EPO while ELIMINATING the undesirable effects of full-length EPO: (1) NO erythropoiesis (red blood cell production — no polycythemia, no increased blood viscosity); (2) NO hypertension (unlike EPO which commonly raises BP); (3) NO thrombosis risk (unlike EPO which increases stroke/MI/DVT risk); (4) NO pure red cell aplasia (PRCA — unlike EPO which rarely causes antibody-mediated severe anemia); (5) NO flu-like symptoms, arthralgias, or myalgias (common EPO side effects). Mechanism: The key insight is that EPO has TWO distinct receptor complexes: (a) the HEMATOPOIETIC RECEPTOR (EPOR homodimer, on bone marrow erythroid progenitors) — mediates red blood cell production; (b) the TISSUE-PROTECTIVE RECEPTOR (TPR, EPOR/βcR heterodimer — EPOR associated with the common beta receptor CD131, shared with IL-3/IL-5/GM-CSF) — expressed on neurons, cardiomyocytes, endothelial cells, immune cells, and mediates cytoprotection, anti-apoptosis, anti-inflammation, and tissue repair. ARA-290 selectively binds to and activates the TISSUE-PROTECTIVE RECEPTOR (EPOR/βcR) but does NOT bind to or activate the HEMATOPOIETIC RECEPTOR (EPOR homodimer). This receptor selectivity allows ARA-290 to retain EPO's beneficial tissue-protective effects without the hematopoietic/cardiovascular side effects. Downstream signaling: JAK2-STAT3/STAT5 (anti-apoptotic, anti-inflammatory gene transcription), PI3K-Akt (Bad/Bax inactivation → anti-apoptotic; eNOS activation → NO ↑ vasodilation; mTOR → survival; GSK-3β inhibition → protection), ERK1/2 (cell survival/proliferation/repair), NF-κB inhibition (TNF-α/IL-1β/IL-6 ↓ anti-inflammatory), and increased antioxidant defenses (SOD/catalase/glutathione ↑, ROS ↓). Main research applications: (1) NEUROPATHIC PAIN (most clinically advanced — diabetic peripheral neuropathy, chemotherapy-induced neuropathy, post-herpetic neuralgia): novel non-opioid, non-NSAID analgesic mechanism via reduced neuronal hyperexcitability (Na+ channel modulation), reduced neuroinflammation (microglia/astrocyte inhibition), neuroprotective effects on peripheral nerves, reduced central sensitization; Phase 2 trial showed significant pain relief at 4 mg/day with excellent safety; (2) WOUND HEALING (diabetic foot ulcers, chronic wounds, burns): promotes angiogenesis (new blood vessels), collagen deposition, re-epithelialization, M1→M2 macrophage polarization, reduced inflammation, reduced oxidative stress; preclinical studies show accelerated wound closure in diabetic models; (3) NEUROPROTECTION (stroke, TBI, spinal cord injury, Alzheimer, Parkinson, MS): anti-apoptotic, anti-inflammatory, antioxidant, neurogenic, synaptic plasticity, BBB protection; preclinical studies show reduced infarct/lesion size and improved function; advantage over EPO: no polycythemia/hypertension/thrombosis (EPO in stroke trials had increased mortality due to thrombosis); (4) CARDIOPROTECTION (myocardial I/R injury, MI, heart failure, diabetic cardiomyopathy, chemotherapy-induced cardiotoxicity): reduced infarct size, reduced cardiomyocyte apoptosis, reduced adverse remodeling/fibrosis, improved cardiac function, mitochondrial protection, endothelial protection; via RISK pathway (PI3K-Akt/ERK1/2); (5) ANTI-INFLAMMATORY conditions (IBD, RA, psoriasis, uveitis): immunomodulation, reduced pro-inflammatory cytokines, M2 macrophage polarization; (6) METABOLIC diseases (type 2 diabetes, metabolic syndrome): improved insulin sensitivity, β-cell protection, reduced metaflammation. Key advantages: (1) SELECTIVE tissue-protective receptor agonist — no hematopoietic receptor activation; (2) NO erythropoiesis — no hemoglobin/hematocrit increase (confirmed in clinical trials); (3) NO polycythemia, NO hypertension, NO thrombosis (major EPO safety concerns absent); (4) NO PRCA risk (small peptide, low immunogenicity); (5) Excellent safety profile from Phase 1/2 trials (no significant adverse effects vs. placebo); (6) Novel non-opioid, non-NSAID analgesic mechanism — no opioid addiction, respiratory depression, constipation, or NSAID GI/renal toxicity; (7) Small peptide (11 aa, ~1.4 kDa) — good tissue penetration, low immunogenicity; (8) N-terminal pyroglutamate modification — improved stability, aminopeptidase resistance, longer half-life (~1-2 hr plasma, but pharmacodynamic effects persist much longer due to downstream signaling); (9) Phase 2 clinical proof-of-concept for neuropathic pain; (10) Preclinical evidence across multiple tissue-protective indications. Limitations: (1) NOT orally bioavailable (requires daily SC injection — or topical for wounds); (2) NOT FDA-approved (clinical development ongoing, Phase 2 completed for neuropathy; Phase 3 not yet conducted); (3) Modest efficacy in some indications (pain relief was significant but not dramatic in Phase 2); (4) Mechanism not fully characterized (the exact EPOR/βcR signaling and the putative "lipolytic receptor" concept in EPO biology is still being elucidated); (5) Limited long-term safety data (clinical trials were 28 days); (6) Variable quality among research peptide suppliers (always verify purity and identity); (7) WADA status unclear (not explicitly banned but athletes should check); (8) Short plasma half-life (~1-2 hr) requiring daily dosing (though pharmacodynamic effects persist). Safety (from clinical trial data): excellent safety profile — common mild side effects: injection site reactions (~5-15%), headache (~5-10%), nausea (~2-5%), fatigue (~2-5%), dizziness (~2-5%), mild flushing (NO-mediated vasodilation); NOTABLY ABSENT (vs. EPO): NO polycythemia/hematocrit increase, NO hypertension, NO thrombosis/stroke/MI, NO PRCA, NO flu-like symptoms, NO arthralgias/myalgias, NO anabolic effects; rare but serious: severe hypersensitivity/anaphylaxis (very rare), severe injection site reactions (usually non-sterile technique), hypotension (theoretical, not reported), renal toxicity (theoretical at very high doses), immunogenicity (possible but low); NOT a steroid (no androgenic effects), NOT a controlled substance (no dependence/addiction); CONTRAINDICATIONS: hypersensitivity, pregnancy, breastfeeding, children under 18; relative: renal/hepatic impairment, elderly with comorbidities, active malignancy, peptide allergy history. Important: ARA-290 is a research peptide for laboratory/investigational use only — NOT for human consumption, pain management, wound healing, bodybuilding, athletic performance enhancement, or self-administration; source from reputable suppliers with HPLC purity + mass spec verification; use sterile technique; if any persistent or severe side effects occur, discontinue and seek medical attention.

Certificate of Analysis — ARA-290 (10mg)

Every production batch undergoes rigorous quality control testing including HPLC purity analysis, mass spectrometry identity verification, endotoxin testing, and sterility verification.

Identity and Purity

  • Product Name: ARA-290 (10mg)
  • Purity (HPLC): ≥99.0%
  • Identity (Mass Spec): Confirmed
  • Appearance: White lyophilized powder
  • Endotoxin: < 0.5 EU/mg (LAL assay)
  • Sterility: Verified by membrane filtration
  • Storage: -20°C, protect from light

Available COA Reports

COA Report

Batch Documentation

Batch documentation is available on request. Certificates from an accredited laboratory are published here once issued.

Lyophilized Powder

Supplied as lyophilized powder for in-vitro laboratory research use.

Purity Specification

Purity specification above 99% by HPLC-MS, as listed on each product page.

Wholesale Box Pricing

One box = ten vials at a single per-vial rate, with volume pricing for labs and distributors.

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