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Comparison

ARA-290 vs SS-31

ARA-290 is healing & repair; SS-31 is mitochondrial & longevity. They are compared here because they are frequently considered against each other, not because they act alike.

ARA-290 SS-31
Class Healing & repair Mitochondrial & longevity
Evidence Clinical trials Clinical trials
Human trials ~6 ~15
Half-life ~2 minutes ~2-4 hours
Reported range 2-4 mg 40-60 mg
Frequency Once daily Once daily
Routes Subcutaneous Subcutaneous
FDA approved No Yes
Research use only Yes No
Banned in sport No No
Studied for Small fibre neuropathy, Neuropathic pain research, Tissue protection Primary mitochondrial myopathy, Barth syndrome, Age-related muscle decline research
Reported side effects Injection-site reactions, Headache, Fatigue Injection-site reactions, Headache, Nausea, Dizziness

ARA-290

ARA-290 corresponds to the helix-B surface region of erythropoietin, the portion that engages the innate repair receptor, a heteromer of the EPO receptor and the beta-common receptor. Because it does not bind the homodimeric EPO receptor that drives erythropoiesis, it delivers anti-inflammatory and neuroprotective signalling without raising haematocrit. Human trials in sarcoidosis-associated small fibre neuropathy reported improvements in neuropathic symptoms and corneal nerve fibre measures.

SS-31

SS-31 is a cell-permeable tetrapeptide that concentrates in the inner mitochondrial membrane, where it binds cardiolipin, the phospholipid essential to cristae structure and electron transport chain organisation. By stabilising cardiolipin interactions it improves respiratory efficiency and reduces reactive oxygen species generation at source rather than scavenging them afterwards. It is among the most clinically advanced compounds on this site, with phase III programmes in primary mitochondrial myopathy and Barth syndrome, though headline endpoints have been mixed.

ARA-290 vs SS-31: common questions

What is the difference between ARA-290 and SS-31?

ARA-290 is healing & repair and SS-31 is mitochondrial & longevity, so they act on different pathways. ARA-290: An 11-amino-acid erythropoietin derivative that keeps the tissue-protective signalling without any effect on red blood cell production. SS-31: A cardiolipin-binding tetrapeptide that has been through multiple phase III trials in mitochondrial disease.

Which has stronger evidence, ARA-290 or SS-31?

They sit at the same evidence level: clinical trials. ARA-290 has about 6 human studies and SS-31 about 15.

Are ARA-290 and SS-31 FDA approved?

Only SS-31 is FDA approved (Barth syndrome, to improve muscle strength in patients weighing at least 30 kg (Forzinity, accelerated approval September 2025)). ARA-290 is not approved for any indication.

References

Regulatory and primary sources

  1. PubChem compound record (CID 91810664) ↗ · structure, identifiers, synonyms
  2. FDA: Unapproved drugs and "research use only" products ↗ · regulatory status of non-approved products
  3. PubChem compound record (CID 11764719) ↗ · structure, identifiers, synonyms
  4. DailyMed: FDA-approved labeling for SS-31 ↗ · indications, dosing, warnings as approved
  5. FDA Drugs@FDA database ↗ · approval history
  6. CAS Registry Number 736992-21-5 ↗ · chemical identity

Published literature

  1. Rendell MS. The time to develop treatments for diabetic neuropathy.Expert Opin Investig Drugs 2021.PubMed 33423557 · doi:10.1080/13543784.2021.1868433
  2. van Velzen M, Heij L, Niesters M, et al.. ARA 290 for treatment of small fiber neuropathy in sarcoidosis.Expert Opin Investig Drugs 2014.PubMed 24555851 · doi:10.1517/13543784.2014.892072
  3. Atkins C, Wilson AM. Managing fatigue in sarcoidosis - A systematic review of the evidence.Chron Respir Dis 2017.PubMed 27507833 · doi:10.1177/1479972316661926
  4. Culver DA, Dahan A, Bajorunas D, et al.. Cibinetide Improves Corneal Nerve Fiber Abundance in Patients With Sarcoidosis-Associated Small Nerve Fiber Loss and Neuropathic Pain.Invest Ophthalmol Vis Sci 2017.PubMed 28475703 · doi:10.1167/iovs.16-21291
  5. Collino M, Thiemermann C, Cerami A, et al.. Flipping the molecular switch for innate protection and repair of tissues: Long-lasting effects of a non-erythropoietic small peptide engineered from erythropoietin.Pharmacol Ther 2015.PubMed 25728128 · doi:10.1016/j.pharmthera.2015.02.005
  6. Dahan A, Dunne A, Swartjes M, et al.. ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density.Mol Med 2013.PubMed 24136731 · doi:10.2119/molmed.2013.00122
  7. Luansritisakul C, Chiang MC, Burns SL, et al.. Peptides in Regenerative Medicine: A Comprehensive Review of Clinical Applications in Tissue Repair and Chronic Pain Management.Curr Pain Headache Rep 2026.PubMed 42635865 · doi:10.1007/s11916-026-01542-z
  8. Brines M, Dunne AN, van Velzen M, et al.. ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes.Mol Med 2015.PubMed 25387363 · doi:10.2119/molmed.2014.00215
  9. Nashine S. Potential Therapeutic Candidates for Age-Related Macular Degeneration (AMD).Cells 2021.PubMed 34572131 · doi:10.3390/cells10092483
  10. Shirley M. Elamipretide: First Approval.Drugs 2026.PubMed 41335372 · doi:10.1007/s40265-025-02269-8
  11. Obi C, Smith AT, Hughes GJ, et al.. Targeting mitochondrial dysfunction with elamipretide.Heart Fail Rev 2022.PubMed 35037146 · doi:10.1007/s10741-021-10199-2
  12. Rowe LW, Akotoye C, Harris A, et al.. Beyond the injection: delivery systems reshaping retinal disease management.Expert Opin Pharmacother 2025.PubMed 40319468 · doi:10.1080/14656566.2025.2496424
  13. Tung C, Varzideh F, Farroni E, et al.. Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential.Int J Mol Sci 2025.PubMed 39940712 · doi:10.3390/ijms26030944
  14. Pavlović N, Križanac M, Kumrić M, et al.. Mitochondrial Dysfunction: The Silent Catalyst of Kidney Disease Progression.Cells 2025.PubMed 40497970 · doi:10.3390/cells14110794
  15. Mendias CL, Awan TM. Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance.Sports Med 2026.PubMed 41966639 · doi:10.1007/s40279-026-02437-0
  16. de Barcelos IP, Emmanuele V, Hirano M. Advances in primary mitochondrial myopathies.Curr Opin Neurol 2019.PubMed 31408013 · doi:10.1097/WCO.0000000000000743

Literature retrieved from PubMed on October 16, 2026, favouring human studies and reviews. Numbered markers in the text show which paper supports which statement; uncited entries are background reading.

Read this first This page compares published reference data. It is not medical advice and not a recommendation to use either compound. Several compounds documented on this site are not approved for human use.