ARA-290
Cibinetide · Cibinetide · pHBSP · Pyroglutamate helix B surface peptide · Helix B surface peptide
EPO-derived peptide targeting the innate repair receptor, trialled for small-fibre neuropathy.
Typical dose
2 mg
once daily
Range
1–4
mg
Half-life
20 min
see Dosing
Evidence
Early human
Subcutaneous
What it is
ARA-290, INN cibinetide, is an 11-amino-acid peptide copied from helix B of erythropoietin, specifically the face of the EPO molecule that points away from the classical EPO receptor. The design is deliberate: it keeps EPO's tissue-protective and anti-inflammatory signalling while removing everything that raises red cell mass.
It works through the innate repair receptor, a heterocomplex of the EPO receptor and the beta-common receptor CD131. That complex only assembles on cells under metabolic stress or injury, so ARA-290 is largely inert in healthy tissue and acts selectively where damage or inflammation is already present.
After thymosin alpha-1 it is the most seriously trialled compound in this group. Randomised, double-blind, placebo-controlled phase 2 studies in sarcoidosis-associated small-fibre neuropathy and in type 2 diabetes both showed improvement in neuropathic symptoms, and the sarcoidosis work also showed an increase in corneal nerve-fibre density, an objective structural marker. Development stalled after phase 2 and it was never approved anywhere.
How it works
ARA-290 binds the EPO-receptor/CD131 heterodimer known as the innate repair receptor, which is only expressed on cells experiencing hypoxia, metabolic stress or injury. Engaging it activates JAK2/STAT3 and PI3K/Akt signalling, switches on anti-apoptotic pathways, suppresses local pro-inflammatory cytokine output, and shifts macrophages away from an inflammatory phenotype.
In nerve tissue this shows up as reduced apoptosis of small unmyelinated C-fibres and measurable regrowth of nerve endings. Because it has essentially no affinity for the EPO-receptor homodimer that drives erythropoiesis, it does not raise haematocrit, red cell mass or thrombotic risk the way EPO does.
Dosing
4 mg daily for 28 days is the dose with actual randomised-trial support. The 1-2 mg protocols common in the community are a cost compromise and sit below the dose that produced the published results.
Reconstitution calculator
Pre-loaded with ARA-290’s vial size, water volume and typical dose. Change anything.
Typical: 2 mg · range 1–4
Draw to
40 u
0.4 mL · 2 mg
Concentration
5 mg/mL
50 mcg per unit
Doses per vial
2.5
Vial lasts
2.5 days
Draw to 40 units on the barrel.
Once mixed
Refrigerate at 2-8 C and use within about 30 days.
1 mL of bacteriostatic water into a 5 mg vial gives 5 mg/mL, so a 2 mg dose is 0.4 mL, or 40 units on a U-100 syringe. Doses here are milligram-scale, so injection volumes are much larger than with most peptides; a larger vial reconstituted at higher concentration keeps the volume manageable.
Storage
Before mixing
Sealed lyophilised vials keep about 24 months at -20 C and several months at 2-8 C.
After mixing
Refrigerate at 2-8 C and use within about 30 days.
Reported benefits
- ▪Reduced neuropathic pain scores in randomised placebo-controlled phase 2 trials
- ▪Increased corneal nerve-fibre density, an objective marker of small-fibre regrowth
- ▪Improved metabolic control and HbA1c in a type 2 diabetes trial
- ▪No effect on haematocrit or red cell mass, unlike EPO itself
- ▪Receptor only assembles on stressed tissue, so off-target activity is low
- ▪Well tolerated across 28-day human dosing periods
Side effects
- ▪Mild injection-site reactions, the most common finding in trials
- ▪Occasional headache
- ▪Transient fatigue during the first days of dosing
- ▪Local discomfort from the large injection volume at milligram-scale doses
- ▪Long-term safety beyond 28 days of continuous use is untested in humans
Do not use if
- ▪Active malignancy, since innate repair receptor signalling is anti-apoptotic and some tumours express the receptor components
- ▪Uncontrolled proliferative retinopathy, on the same anti-apoptotic and pro-angiogenic reasoning
- ▪Pregnancy or breastfeeding, where there is no data
Evidence level — Early human
Small or early-phase human studies only.
Not approved in any market; cibinetide completed phase 2 trials and is now sold only as a research chemical.
Commonly run with
BPC-157
Gastric-juice-derived pentadecapeptide studied for tendon, ligament and gut healing.
250 mcg · 1x daily (some split into 2x daily during an acute injury)
SS-31
Cardiolipin-binding mitochondrial peptide, FDA-approved as elamipretide for Barth syndrome.
10 mg · Once daily
Thymosin Alpha-1
Thymic peptide that tunes T-cell function; licensed abroad as thymalfasin for hepatitis B.
1600 mcg · 2x weekly, spaced 3-4 days apart
ARA-290 FAQ
Will ARA-290 raise my haematocrit like EPO?+
No. It was engineered from the part of the EPO molecule that does not contact the erythropoietic receptor, and human trials measured no change in red cell mass or haematocrit. It carries none of EPO's thrombotic risk and is not a blood-doping agent.
How long before neuropathy symptoms change?+
In the sarcoidosis trial, symptom scores separated from placebo across the 28-day dosing period and corneal nerve density had increased by day 28. Anecdotally the first shift in burning or numbness tends to show up in weeks 2-3, so a course shorter than four weeks is unlikely to tell you much.
Why do community protocols run so far below the trial dose?+
Cost. At 4 mg daily a 28-day course consumes 112 mg of peptide, which is expensive at typical research-chemical pricing. Running 1-2 mg is a reasonable compromise, but be clear with yourself that it is below the dose that produced the published outcomes.
Does it help nerve pain that is not from diabetes or sarcoidosis?+
Animal models cover traumatic nerve injury, chemotherapy-induced neuropathy and ischaemic damage, and the receptor mechanism is not disease-specific. Human evidence is confined to those two populations though, so anything else is extrapolation.
Is it worth stacking with BPC-157?+
They act by different mechanisms, so the pairing is common for nerve-related complaints. BPC-157 has a much larger anecdotal base for peripheral nerve recovery but almost no human data, while ARA-290 has the trial evidence. Neither has been studied in combination with the other.
References
- 1.ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density — Molecular Medicine (2013) PMID 24136731
- 2.Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study — Molecular Medicine (2012) PMID 23168581
- 3.ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes — Molecular Medicine (2015) PMID 25387363
- 4.Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin — Proceedings of the National Academy of Sciences (2008) PMID 18676614
More immune & inflammation
LL-37
The only human cathelicidin: broad antimicrobial and biofilm-disrupting innate immune peptide.
250 mcg · once daily
Thymosin Alpha-1
Thymic peptide that tunes T-cell function; licensed abroad as thymalfasin for hepatitis B.
1600 mcg · 2x weekly, spaced 3-4 days apart
Thymulin
Zinc-dependent thymic nonapeptide studied for T-cell maturation and inflammatory pain.
250 mcg · once daily