Overview
Overview
Ara-290 (cibinetide) is an 11–amino acid non-erythropoietic peptide derived from erythropoietin’s helix-B domain[1]. It selectively activates the innate repair receptor (IRR), an EPOR/CD131 heterodimer, to promote anti-inflammatory and tissue-protective effects without stimulating red blood cell production[2]. Clinical trials have demonstrated benefits for diabetic neuropathy and sarcoidosis-related small-fiber neuropathy[3][4]. Reconstitute: Add 2.0 mL bacteriostatic water → 8 mg/mL concentrat
- Category
- Uncategorized
- Routes
- subcutaneous
Mechanism
Ara-290
Mechanism of action
Mechanism of action
Ara-290 (cibinetide) binds to the innate repair receptor (IRR), a heterodimer of EPOR and CD131 (βc subunit), which is distinct from the classical erythropoietin receptor [1] [2] . This selective binding triggers anti-apoptotic and anti-inflammatory signaling cascades that protect tissues and promote repair without stimulating erythropoiesis [9] . Preclinical research demonstrates that Ara-290 can reprogram a pro-inflammatory, tissue-damaging environment into one favoring healing and regeneration [10] . Additionally, analgesic effects have been observed through immunomodulation and direct inhibition of TRPV1 ion channels activated by capsaicin [11] .
Key research findings
- 01
Identity / structure (biochemical): Ara-290 (INN: cibinetide; also called pyroglutamate helix B surface peptide, pHBSP) is an 11-amino-acid peptide modeled on the helix-B region of erythropoietin (EPO) and is non-erythropoietic — it does not stimulate red-blood-cell production (reviewed by Collino et al., 2015).
- 02
Mechanism (receptor pharmacology / in vitro): Engineered to selectively engage the 'innate repair receptor' (IRR), a heteromeric complex of the EPO receptor and the β-common receptor (CD131), rather than the EPOR homodimer that mediates erythropoiesis.
- 03
Animal models: In rodent studies, including β-common-receptor knockout models (Swartjes et al., 2013), the IRR has been implicated in Ara-290's tissue-protective and innate-immune-modulating readouts; the peptide has a very short plasma half-life (~2 minutes) yet is reported to produce longer-lasting biological effects.
- 04
Human studies (early Phase 2): Small randomized Phase 2 trials in sarcoidosis-associated small-fiber neuropathy reported changes in corneal nerve-fiber measures and patient-reported pain scores (e.g., Culver et al., 2017, n=64); these are early-stage, small-sample datasets.
- 05
Research framing / non-erythropoietic property: The absence of erythropoietic stimulation (no measured rise in hematocrit/hemoglobin) is a repeatedly reported, defining research property; given small human sample sizes, observed effects in research should be interpreted cautiously and do not constitute a safety profile.
Primary source: Ara-290 (cibinetide) has a well-defined preclinical research base — its structure, non-erythropoietic profile, and proposed innate-repair-receptor mechanism are described across multiple reviews and animal studies (e.g., Collino et al., Pharmacology & Therapeutics, 2015; Swartjes et al., 2013). Human evidence is limited and early-stage, consisting mainly of small Phase 2 trials in sarcoidosis-associated small-fiber neuropathy (e.g., Culver et al., 2017); the peptide remains investigational and is not an approved therapy.
Researched Effects
Researched benefits
Areas of active research and investigation. Results may vary and are based on preclinical or early clinical data.
Neuroprotection: Clinical trials in diabetic neuropathy showed improvements in HbA1c, lipid profiles, and neuropathic pain scores with 4 mg daily dosing[3].
Nerve regeneration: In sarcoidosis-associated small-fiber neuropathy, treatment led to significant increases in corneal nerve fiber density (objective nerve regrowth) and improved symptoms compared to placebo[4].
Tissue protection: Anti-inflammatory and anti-apoptotic effects observed across multiple organ systems in preclinical models[9].
Protocol Reference
Protocol reference
Commonly cited research range: 2–4 mg, daily.
Reference figures reported in the research literature — not a dosing recommendation. For interactive vial math and scheduling, see the Calculator and Schedule tabs.
Cited protocol & reconstitution guide
Source-backed reference fields by phase, including any volume fields authored in the cited guide.
Weeks 1–4 (Typical range)
1-4 mg/day
Weeks 1–4 (Higher range cited)
Up to 8 mg/day (trial ceiling)
| Phase | Reference amount | Units / volume |
|---|---|---|
| Weeks 1–4 (Typical range) | 1-4 mg/day | 12.5–50 units (0.12–0.50 mL) |
| Weeks 1–4 (Higher range cited) | Up to 8 mg/day (trial ceiling) | 100 units (1.00 mL) |
Titration protocol
- Weeks 1–4Start1-4 mg/day
Once daily subcutaneous injection (lower abdomen or thigh fat, small insulin syringe). Rotate injection sites to reduce local irritation. Blocks generally run about 4 weeks (28 days) of daily dosing; hold the selected amount for the full block.
- Weeks 1–4MaintenanceUp to 8 mg/day (trial ceiling)
Once daily subcutaneous injection. 8 mg/day is the highest amount reported in protocol blocks — hold at this level, do not exceed. At 8 mg/mL this is a full 100-unit (1.00 mL) draw, the maximum a U-100 syringe holds in one pull.
Storage & Handling
Storage requirements(typical for most peptides)
Can be stored for extended periods. Protect from moisture.
Store in refrigerator door. Never freeze after reconstitution.
Label vials with reconstitution date. Discard if cloudy.
Reconstitution steps
- 01🌡️01 Sanitize — Wipe the vial stopper and BAC water stopper with an alcohol swab.
- 02🧴Draw 2 mL bacteriostatic water into a sterile syringe — this 16 mg vial yields 8 mg/mL.
- 03💉03 Add slowly — Let the water run down the inside wall of the vial, not straight onto the powder.
- 04💧04 Dissolve gently — Swirl, do not shake. Wait until the solution is clear.
- 05🔄05 Inspect — The solution should look clear and colorless. Discard it if it is cloudy or has particles.
- 06🏷️06 Store cold — Label with the reconstitution date and refrigerate the mixed vial at 2–8 °C (35.6–46.4 °F), protected from light.
- 07❄️07 Use within ~14 days — Use the reconstituted vial within about two weeks; discard leftover solution after that.
- 08💉Important: This guide is for educational purposes only and is not medical advice. For research use only. Not for human consumption.
Additional storage notes
Refrigerate at 2–8 °C (35.6–46.4 °F) for up to 2 years; freeze at −20 °C (−4 °F) for extended storage up to 3 years [6] .
Refrigerate at 2–8 °C (35.6–46.4 °F); use within 28 days and do not freeze the liquid solution [7] .
Allow vials to reach room temperature before opening to minimize condensation; protect from light.
Discard if discoloration, cloudiness, or particulate matter is observed.
Clinical Evidence
Clinical evidence
Investigated in preclinical and early clinical research for neuropathic and inflammatory conditions; it does not stimulate erythropoiesis.
Ara-290 (cibinetide) has a well-defined preclinical research base — its structure, non-erythropoietic profile, and proposed innate-repair-receptor mechanism are described across multiple reviews and animal studies (e.g., Collino et al., Pharmacology & Therapeutics, 2015; Swartjes et al., 2013). Human evidence is limited and early-stage, consisting mainly of small Phase 2 trials in sarcoidosis-associated small-fiber neuropathy (e.g., Culver et al., 2017); the peptide remains investigational and is not an approved therapy.
- 01Identity / structure (biochemical): Ara-290 (INN: cibinetide; also called pyroglutamate helix B surface peptide, pHBSP) is an 11-amino-acid peptide modeled on the helix-B region of erythropoietin (EPO) and is non-erythropoietic — it does not stimulate red-blood-cell production (reviewed by Collino et al., 2015).
- 02Mechanism (receptor pharmacology / in vitro): Engineered to selectively engage the 'innate repair receptor' (IRR), a heteromeric complex of the EPO receptor and the β-common receptor (CD131), rather than the EPOR homodimer that mediates erythropoiesis.
- 03Animal models: In rodent studies, including β-common-receptor knockout models (Swartjes et al., 2013), the IRR has been implicated in Ara-290's tissue-protective and innate-immune-modulating readouts; the peptide has a very short plasma half-life (~2 minutes) yet is reported to produce longer-lasting biological effects.
- 04Human studies (early Phase 2): Small randomized Phase 2 trials in sarcoidosis-associated small-fiber neuropathy reported changes in corneal nerve-fiber measures and patient-reported pain scores (e.g., Culver et al., 2017, n=64); these are early-stage, small-sample datasets.
- 05Research framing / non-erythropoietic property: The absence of erythropoietic stimulation (no measured rise in hematocrit/hemoglobin) is a repeatedly reported, defining research property; given small human sample sizes, observed effects in research should be interpreted cautiously and do not constitute a safety profile.
Evidence maturity varies by compound; much peptide research is preclinical (in vitro or animal-model). Where human data are limited, findings should be read as research observations, not clinical conclusions.
References
Literature references
Published research articles and sources related to Ara-290.
- 01IUPHAR/BPS Guide to Pharmacology — Cibinetide (ARA-290) ligand profile: structure, receptor binding, and pharmacology View Source
- 02Molecular Medicine (2008) — Brines & Cerami: Discovery and development of the innate repair receptor and its non-erythropoietic ligands View Sourceet al. (2008)
- 03Molecular Medicine (2014) — Brines M. et al.: ARA 290 improves metabolic control and neuropathic symptoms in patients with type 2 diabetes View Sourceet al. (2014)
- 04Molecular Medicine (2013) — Dahan A. et al.: ARA 290 improves symptoms in sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density View Sourceet al. (2013)
- 05ClinicalTrials.gov (NCT02039687) — Phase 2 study of ARA 290 on corneal nerve fiber density in sarcoidosis (1 mg vs 4 mg vs 8 mg daily SC for 28 days) View Source
- 06NCBI Bookshelf — Stability and storage considerations for lyophilized peptide formulations View Source
- 07USP General Chapters — Pharmaceutical compounding with bacteriostatic water: stability and beyond-use dating View Source
- 08Cleveland Clinic — Subcutaneous injections: where and how to administer at home View Source
- 09Pain Reports (2017) — Davis T. et al.: Targeting the innate repair receptor to treat neuropathy (review of ARA-290 mechanisms) View Sourceet al. (2017)
- 10Investigative Ophthalmology & Visual Science (2016) — Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small fiber neuropathy View Sourceet al. (2016)
- 11Peptides Journal (2016) — Zhang W. et al.: ARA 290 relieves pathophysiological pain by targeting TRPV1 channel View Sourceet al. (2016)
- 12Johns Hopkins Arthritis Center — How to give a subcutaneous injection: patient guide View Source
- 13CDC — Vaccine administration: subcutaneous route (angle, site, and technique guidance) View Source
- 14PMC Subcutaneous Drug Delivery Review — Pharmacologic considerations of the subcutaneous injection route View Source
- 15Pure Lab Peptides — Ara-290 (16 mg) product page (quality and batch documentation) View Source
Research Considerations
Research considerations
Research Use Only - not for human or veterinary therapeutic use. Investigational compound currently in clinical development; not approved for general use. Consult a licensed healthcare professional for any clinical decisions.
Factors noted in the research literature; not patient-specific medical advice.
Regulatory Status
Regulatory status
RUO
Comparisons
Comparisons
| Compound | Mechanism | Route | Status |
|---|---|---|---|
| Ara-290this | An 11-amino-acid non-erythropoietic peptide derived from erythropoietin's helix-B domain that selectively activates the innate repair receptor (an EPOR/CD131 heterocomplex), studied for tissue protection and resolution of inflammation. | subcutaneous | Investigational / RUO |
| BPC-157 | Promotes angiogenesis, accelerates wound healing, and protects organs. Interacts with growth hormone receptors and NO system. | subcutaneous, intramuscular | Investigational / RUO |
| Cagrilintide | A long-acting acylated amylin analog that activates central amylin (calcitonin-family) receptors to promote satiety and slow gastric emptying. | subcutaneous | Investigational / RUO |
| Cartalax | A synthetic tripeptide bioregulator (Ala-Glu-Asp) studied for gene-regulatory activity in connective and cartilage tissue, with proposed anti-inflammatory and regenerative effects. | subcutaneous | Investigational / RUO |
| Cerebrolysin | A porcine brain-derived preparation of low-molecular-weight neuropeptides and free amino acids studied for neurotrophic activity supporting neuronal survival, synaptic plasticity, and modulation of neuroinflammation. | subcutaneous | Investigational / RUO |
| Chonluten | A short tripeptide bioregulator (Glu-Asp-Gly) studied for effects on bronchopulmonary tissue and modulation of inflammatory signaling in monocyte/macrophage models. | subcutaneous | Investigational / RUO |
| CJC-1295 | Binds to GHRH receptors to stimulate GH release. Modified structure provides extended duration of action (up to 7 days). | subcutaneous | Investigational / RUO |
Attributes shown for research comparison only; not a statement of efficacy or therapeutic equivalence.
FAQ
Frequently asked questions
It is an 11-amino-acid peptide (INN cibinetide; also pHBSP) derived from the helix-B region of erythropoietin and engineered to be non-erythropoietic. On this workspace it is handled as a Research Use Only material.
Research describes Ara-290 as designed to activate the innate repair receptor (an EPO-receptor / β-common-receptor complex) without driving red-blood-cell production, distinguishing it from EPO, which signals through the EPO-receptor homodimer. This is a mechanistic research distinction, not a clinical claim.
It is studied as a selective ligand of the innate repair receptor, a pathway associated in the literature with tissue-protective and innate-immune-modulating signaling. This mechanism has been characterized largely in vitro and in animal models.
The evidence base is predominantly preclinical, with a small number of early-phase (Phase 2) human trials, mainly in sarcoidosis-associated small-fiber neuropathy. It is investigational and the human data are limited and early-stage.
It is not approved by the FDA or other major regulators for clinical use and remains an investigational compound; on this workspace it is a research-use-only material. This is regulatory information, not medical advice.
Research-reported ranges vary across the available studies. This workspace does not provide dosing guidance; consult the linked protocol reference for documented research ranges. This is not medical advice.
It is generally supplied as a lyophilized powder and reconstituted with sterile or bacteriostatic water for research handling; lyophilized peptide is commonly stored frozen and protected from light, with reconstituted material refrigerated and used within a limited window per supplier documentation. Note that its very short plasma half-life is a frequently studied property. This is general handling information only, not medical guidance.
Research-use notice
Research Use Only. This educational content and calculation support is intended for private research documentation. It does not provide medical advice, human-use directions, or claims of safety or effectiveness.