ARA-290, also called cibinetide in the pharmacology literature, is a short cyclic peptide engineered from a specific region of the erythropoietin (EPO) molecule known as helix B. Researchers built it to separate two activities that full-length EPO carries together: its well-known stimulation of red blood cell production through the classic erythropoietin receptor homodimer, and a second, tissue-protective signaling activity that appears to run through a different receptor arrangement. Laboratories study ARA-290 as a tool for isolating that second pathway in cell culture and in rodent models of nerve, cardiac and organ injury, without the erythropoiesis-driving effects of the parent hormone.
| Attribute | Detail |
|---|---|
| Name | ARA-290 (cibinetide), also referenced as helix B surface peptide (HBSP) derivative |
| Class | Cyclic 11-amino-acid peptide derived from erythropoietin |
| Origin | Modeled on the outer face of helix B in the tertiary structure of erythropoietin |
| Proposed target | Innate repair receptor, a heterodimer of the erythropoietin receptor and the beta common receptor subunit (CD131) |
| What studies examine | Neuropathic pain and microglial activation, cardiac and vascular injury, organ injury after hemorrhagic shock, peripheral nerve inflammation, in cell and rodent models |
| Form supplied | Lyophilized powder, research use only |
What is the structure of ARA-290?
Erythropoietin is a roughly 165-amino-acid glycoprotein whose tertiary structure includes four helical bundles, one of which, helix B, sits on the surface of the folded protein. ARA-290 is a much smaller synthetic peptide, cyclized through a disulfide-forming substitution, that reproduces the sequence spanning that surface-exposed face of helix B. The rationale, described in detail by Collino and colleagues in their 2015 review of erythropoietin-derived tissue-protective peptides, is that this fragment retains enough of the parent molecule's three-dimensional surface to engage a tissue-protective receptor pathway while lacking the structural features needed to drive red blood cell production through the classic erythropoietin receptor.
What is the innate repair receptor, and how does ARA-290 engage it?
The receptor proposed to mediate ARA-290's activity is described in the literature as a heterodimer combining the erythropoietin receptor (EPOR) with the beta common receptor subunit, CD131, which erythropoietin also shares with several cytokine receptors. This combined receptor, sometimes called the innate repair receptor, is reported to be expressed at low levels in most tissues under normal conditions and upregulated after injury. Collino et al. (2015) summarize evidence that ligands engaging this heterodimer, including ARA-290, activate intracellular signaling distinct from the classic JAK2-STAT5 pathway erythropoietin uses to drive erythropoiesis, without triggering the same hematopoietic response.
What have cell and rodent studies examined in nerve injury models?
Several rodent studies have looked at ARA-290 in models of neuropathic and inflammatory nerve injury. Swartjes et al. (2014) examined ARA-290 in a mouse model of chronic constriction nerve injury, reporting long-lasting relief of pain-related behavior that was coupled with suppression of spinal microglial activation, a cellular marker of neuroinflammation in the spinal cord. Zhang et al. (2016) studied ARA-290 in a rodent model of chronic inflammatory pain and reported that its effects involved the TRPV1 ion channel, a receptor also central to research on capsaicin and heat sensation, pointing to an interaction between immune signaling and nociceptive circuits. Liu et al. (2014) examined ARA-290 in a rat model of experimental autoimmune neuritis, an established model of peripheral nerve inflammation, and reported reduced inflammatory markers alongside indicators of nerve tissue protection.
What have cardiac and organ injury studies examined?
Cardiac and hemorrhagic shock models make up a second cluster of ARA-290 research. Ueba et al. (2010) studied a closely related erythropoietin-derived peptide in a rodent model of cardiac injury, reporting reduced infarct size and preserved cardiac function measures, work that helped establish the broader class of helix B-derived peptides as a research tool in cardioprotection. Ahmet et al. (2013) examined chronic administration of a small nonerythropoietic erythropoietin-sequence peptide in a rat model of post-myocardial-infarction dilated cardiomyopathy, tracking cardiac remodeling and function over an extended observation period. Patel et al. (2011) studied a nonerythropoietic erythropoietin-mimetic peptide in a rat model of hemorrhagic shock, reporting reduced organ injury markers and inflammatory signaling in that acute injury model. Together these studies frame ARA-290 and its close structural relatives as tools for separating tissue-protective signaling from the erythropoiesis-driving activity of the parent hormone in acute and chronic injury models.
How does ARA-290 differ from erythropoietin itself?
Full-length erythropoietin drives red blood cell production through the classic EPOR homodimer and the JAK2-STAT5 signaling cascade, and this hematopoietic activity is well documented across decades of research and clinical use of recombinant erythropoietin. ARA-290 is reported in the studies above to lack meaningful engagement of that homodimer and, correspondingly, to lack the erythropoiesis-stimulating activity of the parent hormone, while retaining activity at the proposed innate repair receptor in the cell and animal models researchers have used to study it. This separation of activities is the reason ARA-290 shows up in the literature as a distinct research peptide rather than a stand-in for erythropoietin.
Handling notes
ARA-290 is supplied as a lyophilized powder for research use. As with other short synthetic peptides, researchers should confirm identity and purity against the lot-specific certificate of analysis before use in an assay, and follow standard bench technique for reconstitution and storage; see peptide storage and stability for temperature, light and freeze-thaw considerations relevant to lyophilized and reconstituted peptides generally. For background on how research peptides are built and characterized more broadly, see what is a peptide. Lot-specific specs and the current certificate of analysis for research-grade ARA-290 are posted on our ARA-290 lot page.
Frequently asked questions
Is ARA-290 the same molecule as erythropoietin?
No. ARA-290 is a much smaller cyclic peptide modeled on one surface-exposed helix of erythropoietin's tertiary structure, not the full 165-amino-acid protein. Studies describe it as retaining a subset of erythropoietin's signaling activity while lacking the structural elements associated with erythropoiesis.
Does ARA-290 stimulate red blood cell production the way erythropoietin does?
The cited studies report that ARA-290 does not meaningfully engage the classic erythropoietin receptor homodimer responsible for driving red blood cell production, which is the basis researchers give for using it to study tissue-protective signaling in isolation from that hematopoietic activity.
What is the innate repair receptor?
It is a proposed heterodimer combining the erythropoietin receptor with the beta common receptor subunit (CD131), described in the reviewed literature as upregulated in tissues after injury and as the candidate receptor for ARA-290's activity separate from classic erythropoietin signaling.
What models have researchers used to study ARA-290?
Published studies span rodent models of neuropathic pain and peripheral nerve inflammation, cardiac injury and remodeling, and organ injury following hemorrhagic shock, along with cell-based signaling assays examining the innate repair receptor pathway.
How is ARA-290 supplied for laboratory use?
As a lyophilized powder intended for research use only, sold by lot with an accompanying certificate of analysis, consistent with how other short research peptides on this site are supplied.
References
- Ueba H, Brines M, Yamin M, et al. Cardioprotection by a nonerythropoietic, tissue-protective peptide mimicking the 3D structure of erythropoietin. Proc Natl Acad Sci U S A. 2010;107(32):14357-14362. PubMed 20660739.
- 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;151:32-40. PubMed 25728128.
- Patel NS, Nandra KK, Brines M, et al. A nonerythropoietic peptide that mimics the 3D structure of erythropoietin reduces organ injury/dysfunction and inflammation in experimental hemorrhagic shock. Mol Med. 2011;17(9-10):883-892. PubMed 21607291.
- Swartjes M, van Velzen M, Niesters M, et al. 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. Mol Pain. 2014;10:13. PubMed 24529189.
- Liu Y, Luo B, Han F, et al. Erythropoietin-derived nonerythropoietic peptide ameliorates experimental autoimmune neuritis by inflammation suppression and tissue protection. PLoS One. 2014;9(3):e90942. PubMed 24603865.
- Zhang W, Yu G, Zhang M. ARA 290 relieves pathophysiological pain by targeting TRPV1 channel: integration between immune system and nociception. Peptides. 2016;76:73-79. PubMed 26774587.
- Ahmet I, Tae HJ, Brines M, et al. Chronic administration of small nonerythropoietic peptide sequence of erythropoietin effectively ameliorates the progression of postmyocardial infarction-dilated cardiomyopathy. J Pharmacol Exp Ther. 2013;345(3):446-456. PubMed 23584743.
Research use only. Homegrown Peptides products are for laboratory research and are not for human or animal use. Nothing in this article is medical advice.
