ARA-290 (Cibinetide)

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What Is ARA-290?

ARA-290 (cibinetide) is an 11-amino-acid linear synthetic peptide corresponding to the aqueous-exposed face of helix B of human erythropoietin (EPO) — a region of the EPO molecule that is not involved in binding the classical homodimeric EPO receptor (EPOR₂) that drives red-blood-cell production. ARA-290 was rationally designed by Michael Brines and Anthony Cerami at Araim Pharmaceuticals to dissociate two pharmacologically distinct EPO activities that had historically been entangled in a single molecule: erythropoiesis (the hematocrit-raising effect that limits EPO’s use as a tissue-protective agent because of thromboembolic risk) and tissue protection (the anti-inflammatory, anti-apoptotic, and repair-promoting effects mediated by a distinct heteromeric receptor).

By restricting the peptide sequence to the helix-B surface face, ARA-290 retains affinity for the innate repair receptor (IRR) — a heterocomplex composed of the EPO receptor (EPOR) subunit and the beta-common receptor (βcR, CD131; the shared signalling subunit of the GM-CSF, IL-3, and IL-5 receptors) — while abolishing binding to the EPOR₂ homodimer responsible for erythropoiesis. The net effect is a peptide that produces EPO’s cytoprotective, anti-inflammatory, and neuroprotective effects in tissue without elevating hematocrit or carrying the thromboembolic and hypertensive risks that constrain therapeutic EPO use.

ARA-290 has a short plasma half-life of approximately 2 minutes — the molecule is rapidly cleared — but the biological effect persists for 24–72 hours through downstream activation of cytoprotective signalling cascades (JAK2/STAT3, PI3K/Akt, anti-apoptotic Bcl-2 family upregulation). This pharmacokinetic profile is characteristic of receptor-trigger peptides where the duration of effect is driven by signal-cascade kinetics rather than by sustained plasma levels. ARA-290 has held orphan-drug designation in the United States and the European Union for sarcoidosis-associated small-fiber neuropathy, and has been evaluated in multiple Phase 2 clinical trials in diabetic neuropathy and sarcoidosis-associated neuropathic pain. It is not approved for human therapeutic use by the FDA, EMA, MHRA, or any other major regulator. The research-grade ARA-290 sold here is supplied uitsluitend voor laboratoriumonderzoek and is not intended for human or veterinary administration.

Mechanism of Action — Innate Repair Receptor Agonism Without Erythropoiesis

What makes ARA-290 pharmacologically distinctive is that it activates the cytoprotective limb of erythropoietin signalling while bypassing the erythropoietic limb. Three mechanisms are documented in published research:

• Innate repair receptor (IRR) agonism — EPOR + βcR / CD131 heterocomplex — Under inflammatory or hypoxic-injury conditions, tissue cells upregulate the beta-common receptor (βcR, CD131) and assemble a heterocomplex with the EPO receptor (EPOR). This IRR heterocomplex is the molecular target of ARA-290. Binding triggers JAK2 phosphorylation and downstream STAT3 / STAT5 / PI3K-Akt activation, leading to upregulation of anti-apoptotic proteins (Bcl-2, Bcl-xL), suppression of pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6), and recruitment of tissue-repair programmes. Because the IRR is upregulated locally at sites of injury or inflammation rather than constitutively expressed, ARA-290 acts as a context-restricted agonist that activates repair signalling specifically where it is needed.
• No binding to homodimeric EPOR₂ — no erythropoiesis — The classical erythropoietic receptor on bone-marrow erythroid progenitors is a homodimer of two EPOR subunits without CD131 involvement. ARA-290 has negligible affinity for this homodimer, which is why repeated dosing in clinical trials produces no detectable change in hemoglobin, hematocrit, or reticulocyte count. This is the central design feature that distinguishes ARA-290 from full-length EPO and from earlier engineered EPO analogs (darbepoetin, CERA) that retained erythropoietic activity.
• Downstream anti-inflammatory and tissue-repair effects — In preclinical and clinical research, ARA-290 reduces pro-inflammatory cytokine production by activated macrophages, lowers neuropathic-pain scores in small-fiber neuropathy models, accelerates corneal wound healing, reduces ischemia-reperfusion injury in renal and cardiac models, and improves glycemic control in type 2 diabetes preclinical models. The breadth of effect reflects the broad tissue distribution of the IRR under inflammatory conditions rather than a tissue-specific mechanism.

The short plasma half-life (~2 minutes) combined with sustained biological effect (24–72 hours) means ARA-290 research protocols typically use daily or every-other-day dosing despite the rapid molecular clearance — the pharmacodynamic duration is set by the downstream signalling cascade, not by plasma residence. Subcutaneous administration is the standard research route and the route used in clinical development.

Published Research Applications

ARA-290 is used in laboratory research contexts that investigate:

• Diabetic neuropathy and small-fiber neuropathy research — corneal nerve-fiber density assessment, intra-epidermal nerve-fiber density (IENFD), neuropathic-pain scoring; lead clinical research indication, with Phase 2 trials in type 2 diabetic neuropathy showing improvement in nerve-fiber regeneration and pain scores
• Sarcoidosis-associated small-fiber neuropathy — the indication for which ARA-290 holds US and EU orphan-drug designation; preclinical and Phase 2 research in granulomatous inflammation models
• Neuropathic pain research — chemotherapy-induced peripheral neuropathy, post-surgical neuropathy, mechanistic dissection of IRR-mediated pain pathways
• Ischemia-reperfusion injury research — renal, cardiac, and cerebral ischemia-reperfusion models; anti-apoptotic and anti-inflammatory effect characterisation
• Inflammation and innate immunity research — macrophage polarisation, cytokine-suppression assays, IRR-dependent vs IRR-independent signalling dissection
• Type 2 diabetes metabolic research — glycemic control, beta-cell preservation, comparison against insulin-sensitising mechanisms
• Corneal wound-healing and ophthalmic research — corneal epithelial wound closure rate, nerve-fiber regeneration in the cornea (one of the most densely innervated tissues and a sensitive readout for IRR-driven repair)

For broader context on related anti-inflammatory and tissue-repair research peptides, see BPC-157 (gastric peptide-derived MSK/GI tissue repair), TB-500 (Thymosin Beta-4 fragment, broad tissue repair), and KPV (α-MSH-derived anti-inflammatory tripeptide). Browse the full onderzoekspeptiden catalogus voor gerelateerde verbindingen.

Beschikbare sterktes en concentraties

MedsBase stocks ARA-290 in 10 mg lyophilized vials calibrated to typical research protocol lengths. Available in 10-vial or 20-vial pack formats with full reconstitution guidance:

Clinical Phase 2 doses in published trials are 4 mg subcutaneous daily for diabetic neuropathy and sarcoidosis-associated neuropathy, so a single 10 mg research-grade vial represents a multi-day supply of clinical-equivalent dosing for in-vivo work. ARA-290 is supplied as the unmodified linear 11-mer — there is no acyl chain, no PEGylation, no disulfide bridge, and reconstitution is straightforward relative to longer or modified peptides.

How It Compares — ARA-290 vs BPC-157

ARA-290 and BPC-157 are both used in tissue-repair and anti-inflammatory research, but the two peptides target entirely different molecular machinery. ARA-290 is an EPO-derived innate-repair-receptor agonist that drives JAK2/STAT3 cytoprotective signalling. BPC-157 is a 15-amino-acid synthetic stable gastric pentadecapeptide derived from a fragment of human gastric juice protein BPC, acting through a complex multi-pathway mechanism including nitric oxide synthase modulation, VEGF upregulation, and growth-factor-receptor cross-talk.

For research focused on neuropathic-pain, peripheral-nerve regeneration, or IRR-mediated cytoprotection, ARA-290 is the targeted reference peptide. For research focused on musculoskeletal tendon/ligament repair or gastrointestinal mucosal healing, BPC-157 remains the more widely-studied option. The two peptides are sometimes combined in research protocols that aim to recruit complementary repair pathways across both CNS/peripheral-nerve tissue and connective tissue. See also TB-500 (Thymosin Beta-4 fragment, broad tissue-repair benchmarking) and KPV (α-MSH-derived anti-inflammatory tripeptide).

Opslag en Reconstituering

Voor reconstituering: store lyophilized vials refrigerated at 2–8 °C in original packaging for short-term working stock. For unopened long-term storage, freeze at −20 °C. Lyophilized ARA-290 is stable under refrigeration for up to 24 months and at −20 °C for up to 36 months. Avoid freeze-thaw cycles on the lyophilized powder. ARA-290 is an unmodified linear peptide with no disulfide bridge or acyl chain, so handling is straightforward relative to structurally complex peptides like cagrilintide or semaglutide.

Reconstitueringsprocedure: inject bacteriostatic water down the side wall of the vial (not directly onto the lyophilized cake). For a 10 mg vial, 2.0 mL of bacteriostatic water yields a 5 mg/mL working concentration — 0.08 mL delivers 400 mcg (a 1 mg dose requires 0.2 mL); 0.8 mL delivers a clinical-equivalent 4 mg research dose. Swirl gently — do not shake vigorously, as foaming entrains air and can denature peptide chains. Allow the powder to dissolve fully (typically <1 minute for ARA-290) before withdrawing. Once reconstituted, store the vial at 2–8 °C and use within 14–28 days. Protect from light. Discard if cloudiness, particulates, or colour change appears.

Veelgestelde vragen

Is ARA-290 an EPO analog? Does it raise hematocrit?

ARA-290 is derived from helix B of erythropoietin, but it is engineered specifically to niet raise hematocrit. The classical erythropoietic effect of EPO is mediated by the homodimeric EPO receptor (EPOR₂) on bone-marrow erythroid progenitors. ARA-290 binds the heteromeric innate repair receptor (EPOR + βcR/CD131) instead, and has negligible affinity for EPOR₂. Published Phase 2 trials show no change in hemoglobin, hematocrit, or reticulocyte count after repeated dosing.

What is the innate repair receptor (IRR)?

The innate repair receptor is a heterocomplex of the EPO receptor (EPOR) subunit and the beta-common receptor (βcR, also known as CD131 — the shared signalling subunit of the GM-CSF, IL-3, and IL-5 receptors). The IRR is upregulated locally on stressed, injured, or inflamed tissue rather than expressed constitutively, which is why ARA-290 acts as a context-restricted tissue-repair signal rather than a systemic agonist.

Why is ARA-290 also called cibinetide?

ARA-290 is the developmental code assigned by Araim Pharmaceuticals (the original developer). Cibinetide is the INN (international nonproprietary name) assigned later for clinical-trial and regulatory contexts. The two names refer to the same 11-amino-acid peptide (CAS 1208243-50-8).

Why is the plasma half-life so short relative to the duration of effect?

ARA-290 has a plasma half-life of approximately 2 minutes — the peptide is cleared rapidly from circulation — but the biological effect persists for 24–72 hours through downstream activation of JAK2/STAT3, PI3K/Akt, and anti-apoptotic Bcl-2-family signalling cascades. This pharmacokinetic profile is typical of receptor-trigger peptides where duration is set by signal-cascade kinetics rather than by sustained plasma levels.

How does ARA-290 compare to BPC-157 for tissue repair research?

Both peptides are used in tissue-repair research but target different machinery and different tissues. ARA-290 acts via the innate repair receptor (EPOR + CD131) and is best-characterised in peripheral-nerve, corneal, and ischemic-tissue research. BPC-157 acts through a multi-pathway mechanism involving nitric oxide synthase modulation and VEGF upregulation, and is best-characterised in tendon, ligament, gut mucosal, and muscle research. Some protocols combine the two peptides to recruit complementary repair pathways.

What is sarcoidosis-associated small-fiber neuropathy and why is ARA-290 orphan-designated for it?

Sarcoidosis is a granulomatous inflammatory disease that produces a debilitating small-fiber neuropathy (SFN) in a substantial fraction of affected patients. ARA-290 holds US FDA and EU EMA orphan-drug designation for sarcoidosis-associated SFN, reflecting the rarity of the indication and the absence of other targeted treatments. The orphan designation supports clinical research but does not constitute approval — ARA-290 is investigational at the time of this writing.

What is the standard research dose for ARA-290?

Published Phase 2 clinical trials have used 2–4 mg subcutaneous daily for diabetic neuropathy and sarcoidosis-associated SFN. Preclinical animal studies have used wider dose ranges depending on model and tissue. Researchers should determine dose ranges from peer-reviewed literature appropriate to their specific protocol.

Does ARA-290 require special handling because of the disulfide or acyl modifications?

No. ARA-290 is an unmodified linear 11-amino-acid peptide with no disulfide bridge, no fatty-acid acylation, and no PEGylation. Reconstitution and handling are straightforward — gentle swirling dissolves the lyophilized powder within ~1 minute. Compare this to structurally complex peptides like cagrilintide (acyl chain + disulfide), semaglutide (acyl chain), or insulin-class peptides where reconstitution requires longer equilibration.

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