ARA-290

ARA-290 (also called cibinetide) is a synthetic peptide best known for research into nerve pain and tissue protection, including nerve pain linked to the rare disease sarcoidosis. It's derived from part of the natural hormone erythropoietin (EPO), but unlike EPO, it's designed not to raise red blood cell counts. It is not FDA-approved for any use, though it has been tested in several small human trials and holds FDA orphan-drug status for sarcoidosis-related nerve pain.

ARA-290 has been studied mainly for nerve pain and tissue protection, tested in small Phase 2 human trials. A pilot in sarcoidosis patients with small-fiber neuropathy reported reduced neuropathy symptom scores versus placebo, and a Phase 2 trial in type 2 diabetes reported improved HbA1c, lipids, and neuropathic symptoms. A later Phase 2 trial in diabetic macular edema was safe but did not improve its main vision endpoints. The trials are small, the program did not reach large pivotal trials, and the compound is not approved — so these are early clinical findings, not settled results.

Not FDA-approved for any indication. Investigational. ARA-290 (cibinetide) was developed by Araim Pharmaceuticals and holds FDA Orphan Drug Designation and Fast Track Designation for sarcoidosis-associated small-fiber neuropathy (US), plus EU Orphan Drug Designation for sarcoidosis. It reached Phase 2 in several indications but has not received marketing approval in any jurisdiction, and development appears to have since stalled — no ARA-290 clinical trial has started since 2016 and no Phase 3 program or active US IND could be identified. WADA status: ARA-290 is not explicitly named on the Prohibited List, but as a research peptide with no regulatory approval anywhere it is captured under S0 (Non-Approved Substances) — prohibited at all times — the same basis that applies to BPC-157. Because ARA-290 is non-erythropoietic by design, the S2 "agents affecting erythropoiesis" logic does not cleanly apply; S0 is the governing basis. Athletes should verify with their anti-doping organization. Not DEA-scheduled.

ARA-290 is not FDA-approved, and its safety in humans has been studied only in small, short trials — long-term safety is not established. It is not explicitly named on the WADA Prohibited List, but as a research peptide with no regulatory approval it falls under the S0 (non-approved substances) category, meaning it is prohibited in regulated sport at all times — the same basis that applies to BPC-157. Anyone in regulated sport should verify with their anti-doping organization. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ For research and educational purposes only. ARA-290 (cibinetide) is not approved by the FDA for any indication. It is an investigational peptide that reached Phase 2 trials and holds FDA orphan-drug designation for sarcoidosis-associated neuropathy, but it has never received marketing approval. Information in this entry is informational, not medical advice. Always confirm dose calculations with the in-app calculator and consult appropriate professional guidance before any protocol decisions.

⚠️ Note on evidence base. Unlike the FDA-approved GLP-1 peptides covered elsewhere in this library, ARA-290's human evidence consists of a small number of Phase 2 trials (tens of participants each) plus preclinical animal and cell studies. Several of the human trials were sponsored by, or co-authored by employees of, the originating company (Araim Pharmaceuticals) — a normal feature of early drug development, but worth noting when weighing the evidence. The mechanisms, efficacy signals, and dose patterns described here should be read with those limitations in mind.

⚠️ Derived from EPO, but engineered to avoid raising red blood cells. ARA-290 is built from the "helix B surface" region of erythropoietin and is described in the literature as non-erythropoietic — it is intended to activate a tissue-protective/anti-inflammatory receptor without stimulating red-blood-cell production. It is not explicitly named on the WADA Prohibited List, but as a research peptide with no regulatory approval it is captured under S0 (Non-Approved Substances) and is prohibited at all times — the same basis that applies to BPC-157. Note that because ARA-290 is non-erythropoietic, the S2 "agents affecting erythropoiesis" logic does not cleanly apply; S0 is the governing basis. Researchers in regulated sport should verify with their anti-doping organization.

ARA-290, also known as cibinetide, is a synthetic 11-amino-acid peptide engineered from the three-dimensional structure of erythropoietin (EPO) — specifically the "helix B surface" region. It was developed by Araim Pharmaceuticals (Tarrytown, NY) and the laboratories associated with Anthony Cerami and Michael Brines, who pioneered the concept of separating EPO's tissue-protective activity from its red-blood-cell-stimulating activity.[¹][³] The design goal was a compound that activates a tissue-protective, anti-inflammatory pathway without the erythropoietic (and thrombotic) effects that limit EPO itself.

Mechanism. ARA-290 is described as a selective agonist of the "innate repair receptor" (IRR) — characterized in the literature as a heteromeric receptor formed from the EPO receptor and the β-common receptor (CD131).[¹][³] Activation of this receptor is reported to arrest tissue injury and promote anti-inflammatory and cytoprotective responses. In preclinical work, ARA-290 has been reported to reduce neuropathic pain (allodynia) in a rat spared-nerve-injury model while suppressing the spinal microglia response — suggesting a link between central inflammation and pain relief.[⁴] A separate preclinical study reported that ARA-290 can inhibit the TRPV1 ion channel, proposing an additional peripheral mechanism for its analgesic effects.[⁶] ARA-290 has also been reported to inhibit macrophage activation and protect transplanted pancreatic islets from cytokine-induced damage in animal models.[⁸]

Evidence quality. The human evidence base consists of small Phase 2 trials: - A randomized, double-blind, placebo-controlled pilot in sarcoidosis patients with small-fiber neuropathy (22 patients; IV ARA-290 vs placebo) reported a significant improvement in the small-fiber-neuropathy symptom score and in the pain and physical-functioning dimensions of the SF-36 versus placebo, with no safety concerns raised.[¹] - A larger randomized, placebo-controlled trial in sarcoidosis-associated small-fiber neuropathy using 28 days of daily subcutaneous dosing reported improved neuropathic symptoms, an increase in corneal small-nerve-fiber density, and improved 6-minute-walk distance.[⁷] This is the study behind the frequently repeated claim that ARA-290 regenerates small nerve fibers, and it is the subcutaneous counterpart to the earlier IV pilot above. - A Phase 2 study in type 2 diabetes ( subcutaneous for 28 days, with a further month of follow-up) reported improvements in HbA1c and lipid profiles, improvement on the PainDetect neuropathy questionnaire, and an increase in corneal nerve fiber density in subjects who started with reduced density, with no safety issues identified.[³] - A Phase 2 trial in diabetic macular edema (cibinetide subcutaneous for 12 weeks, 9 patients) found the course safe with no anti-drug antibodies, but did not improve its primary vision endpoints (visual acuity, central retinal thickness); some participants showed exploratory improvements warranting further study.[⁵]

A clinical review summarized the sarcoidosis and broader neuropathy data and described the safety profile as favorable while emphasizing the need for additional, larger studies.[²] No large pivotal (Phase 3) trial has been published, and the compound is not approved anywhere. The clinical evidence base has also not grown: no new ARA-290 human trial has been published since roughly 2017, and no interventional trial has started since 2016. Development appears to have stalled rather than advanced.

Regulatory status (US). ARA-290 is not FDA-approved for any indication. It holds FDA Orphan Drug Designation and Fast Track Designation for sarcoidosis-associated small-fiber neuropathy, plus EU Orphan Drug Designation for sarcoidosis (orphan/fast-track designation is not the same as marketing approval). Not DEA-scheduled. It is available in the US only as a research-supply peptide outside the FDA-recognized supply chain.

Regulatory status (sport — WADA). ARA-290 is not explicitly named on the WADA Prohibited List, but as a research peptide with no regulatory approval in any jurisdiction it is captured under S0 (Non-Approved Substances), which makes it prohibited at all times — the same basis that applies to BPC-157. Importantly, although ARA-290 is derived from EPO, it is non-erythropoietic by design, so the S2 "agents affecting erythropoiesis" logic does not cleanly apply; S0 is the governing basis here. Users in regulated sport should verify current WADA status directly via the WADA Prohibited List and their National Anti-Doping Organization before any use.

Common research interests. Despite the limited and early clinical evidence base, ARA-290 is discussed in the research community primarily for: - Small-fiber and peripheral neuropathy symptom relief (the largest human evidence base, in sarcoidosis and diabetes)[¹][³] - Neuropathic pain more broadly (preclinical and clinical analgesia signals)[²][⁴][⁶] - Anti-inflammatory / tissue-protective applications (preclinical macrophage and islet-protection work) - Metabolic adjunct use (the type-2-diabetes HbA1c/lipid signals)[³]

These uses are extrapolated from small trials and preclinical data; they are not FDA-approved indications.

Commonly reported

• Injection-site reactions (local redness, soreness) — typical of subcutaneous injection
• No consistent pattern of serious adverse events in the published trial literature[¹][³][⁵]
• EPO lineage. Although ARA-290 is engineered to be non-erythropoietic, it is derived from EPO; researchers should be aware of the theoretical framing around EPO-family compounds and circulatory effects, even though the published trials did not report erythropoietic activity.
• Long-term safety in humans is essentially unknown. The longest published exposures are on the order of weeks; no multi-year human safety dataset exists.

Pregnancy and lactation — no data; default to contraindicated

Pediatric use — no data; should not be used in researchers under 18

Active malignancy — caution; tissue-protective/anti-inflammatory signaling effects in the cancer context are not characterized

Known hypersensitivity to the peptide — contraindicated

Regulatory note (US): ARA-290 is not FDA-approved and is available only as a research-supply peptide outside the FDA-recognized supply chain.

Regulatory note (sport): ARA-290 is not explicitly named on the WADA Prohibited List but is captured under S0 (non-approved substances), prohibited at all times — the same basis as BPC-157. Because it is non-erythropoietic, the S2 erythropoiesis logic does not cleanly apply. Verify with your anti-doping organization before use.

Not DEA-scheduled.

Peptide

A short chain of amino acids, the building blocks of proteins. Many compounds in this library are peptides.

Erythropoietin (EPO)

A natural hormone that signals the body to make red blood cells. ARA-290 is derived from a part of EPO but is engineered to skip that blood-cell effect.

Subcutaneous

An injection into the fatty layer just under the skin, rather than into a muscle or vein.

Phase 2 trial

A mid-stage human study that tests whether a treatment works and looks for side effects, usually in a few dozen to a few hundred people.

Half-life

How long it takes for half of a substance to clear from the blood. A short half-life does not always mean a short biological effect.

1. Heij L, Niesters M, Swartjes M, Hoitsma E, Drent M, Dunne A, Grutters JC, Vogels O, Brines M, Cerami A, Dahan A. (2012). Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Molecular Medicine, 18(1):1430–1436.(PMID 23168581)
2. van Velzen M, Heij L, Niesters M, Cerami A, Dunne A, Dahan A, Brines M. (2014). ARA 290 for treatment of small fiber neuropathy in sarcoidosis. Expert Opinion on Investigational Drugs, 23(4):541–550.(PMID 24555851)
3. Brines M, Dunne AN, van Velzen M, Proto PL, Ostenson CG, Kirk RI, Petropoulos IN, Javed S, Malik RA, Cerami A, Dahan A. (2015). ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes. Molecular Medicine, 20(1):658–666.(PMID 25387363)
4. Swartjes M, van Velzen M, Niesters M, Aarts L, Brines M, Dunne A, Cerami A, Dahan A. (2014). ARA 290, a peptide derived from the tertiary structure of erythropoietin, produces long-term relief of neuropathic pain coupled with suppression of the spinal microglia response. Molecular Pain, 10:13.(PMID 24529189)
5. Lois N, Gardner E, McFarland M, Armstrong D, McNally C, Lavery NJ, Campbell C, Kirk RI, Bajorunas D, Dunne A, Cerami A, Brines M. (2020). A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema. Journal of Clinical Medicine, 9(7):2225.(PMID 32674280)
6. Zhang W, Yu G, Zhang M. (2016). ARA 290 relieves pathophysiological pain by targeting TRPV1 channel: Integration between immune system and nociception. Peptides, 76:73–79.(PMID 26774587)
7. Dahan A, Dunne A, Swartjes M, Proto PL, Heij L, Vogels O, van Velzen M, Sarton E, Niesters M, Tannemaat MR, Cerami A, Brines M. (2013). ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Molecular Medicine, 19(1):334–345.(PMID 24136731)
8. Watanabe M, Lundgren T, Saito Y, Cerami A, Brines M, Östenson CG, Kumagai-Braesch M. (2016). A Nonhematopoietic Erythropoietin Analogue, ARA 290, Inhibits Macrophage Activation and Prevents Damage to Transplanted Islets. Transplantation, 100(3):554–562.(PMID 26683514)

• BPC-157 / TB-500 Blend — discussed together in this entry's stacks section
• BPC-157 — same mechanism class
• GHK-Cu — same mechanism class
• GLOW — same mechanism class
• KLOW — same mechanism class
• TB-500 — same mechanism class