ARA-290 (cibinetide)

Quick answers

Molecular Profile

Type

Synthetic linear 11-amino-acid non-erythropoietic helix-B surface peptide

Molecular formula

C51H84N16O21

Molecular weight

~1,257.3 g/mol

CAS number

1208243-50-8

Amino acids

11

Sequence

pGlu-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser

Modification

N-terminal pyroglutamate (pGlu)

Mechanism & Target Class

ARA-290 is a synthetic peptide derived from the three-dimensional helix-B surface region of erythropoietin (EPO). EPO biology involves two functionally distinct receptor configurations: a homodimeric EPOR/EPOR complex mediating erythropoiesis in erythroid progenitor cells, and a heteromeric EPOR/CD131 (beta-common receptor, βcR) complex — termed the innate repair receptor (IRR) or tissue-protective receptor — that shares the CD131 signaling subunit with the GM-CSF, IL-3, and IL-5 receptors. The foundational EPOR/CD131 heterocomplex characterization was reported by Brines et al. (2004); short tissue-protective helix-B peptide sequences, including the 11-amino-acid precursor of ARA-290, were delimited by Brines et al. (2008). In preclinical cellular systems, IRR engagement is associated with downstream JAK2/STAT3, PI3K/Akt, and ERK pathway activation and with anti-apoptotic transcriptional responses. Mechanistic literature describes IRR expression as locally upregulated in injured, hypoxic, or inflamed tissue rather than constitutively expressed at high levels. ARA-290 has also been reported to interact with TRPV1 channel activity in nociception model systems (Zhang et al., 2016), proposing a direct nociceptor mechanism alongside IRR-mediated anti-inflammatory signaling.

Storage & Handling

Lyophilized

Lyophilized powder: −20°C or below; −80°C recommended for long-term archival.

Handling

Water-soluble. Avoid repeated freeze-thaw cycles. For research use only.

Primary Database

PubChem CID 91810664 ↗

References (27)

1. Reviews

   1

   Collino M, Thiemermann C, Cerami A, Brines M. (2015). Pharmacology & Therapeutics

   DOI: 10.1016/j.pharmthera.2015.02.005PubMed 25728128

2. 2

   van Velzen M, Heij L, Niesters M, Cerami A, Dunne A, Dahan A, Brines M. (2014). Expert Opinion on Investigational Drugs

   DOI: 10.1517/13543784.2014.892072

3. 3

   Brines M, Cerami A. (2012). Molecular Medicine

   DOI: 10.2119/molmed.2011.00414PubMed 22183892

4. Clinical

   4

   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). Journal of Clinical Medicine

   DOI: 10.3390/jcm9072225PubMed 32674280NCT06626971

5. 5

   Culver DA, Dahan A, Bajorunas D, Jeziorska M, van Velzen M, Aarts LPHJ, Tavee J, Tannemaat MR, Dunne AN, Kirk RI, Petropoulos IN, Cerami A, Malik RA, Brines M. (2017). Investigative Ophthalmology & Visual Science

   DOI: 10.1167/iovs.16-21291PubMed 28475703NCT02039687

6. 6

   Brines M, Dunne AN, van Velzen M, Proto PL, Ostenson CG, Kirk RI, Petropoulos IN, Javed S, Malik RA, Cerami A, Dahan A. (2015). Molecular Medicine

   DOI: 10.2119/molmed.2014.00215PubMed 25387363

7. 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). Molecular Medicine

   DOI: 10.2119/molmed.2013.00122PubMed 24136731

8. 8

   Heij L, Niesters M, Swartjes M, Hoitsma E, Drent M, Dunne A, Grutters JC, Vogels O, Brines M, Cerami A, Dahan A. (2012). Molecular Medicine

   DOI: 10.2119/molmed.2012.00332PubMed 23168581

9. 9

   ClinicalTrials.gov. ClinicalTrials.gov

   NCT02070783

10. 10

    ClinicalTrials.gov. ClinicalTrials.gov

    NCT01933529

11. Primary research

    11

    Winicki NM, et al. (2023). Frontiers in Cardiovascular Medicine

    DOI: 10.3389/fcvm.2022.1096887PubMed 36741836

12. 12

    Xu G, Zou T, Deng L, Yang G, Guo T, Wang Y, Niu C, Cheng Q, Yang X, Dong J, Zhang J. (2022). Frontiers in Pharmacology

    DOI: 10.3389/fphar.2022.896601PubMed 36046815

13. 13

    Yao M, Domogatskaya A, Ågren N, Watanabe M, Tokodai K, Brines M, Cerami A, Ericzon BG, Kumagai-Braesch M, Lundgren T. (2021). Cell Transplantation

    DOI: 10.1177/09636897211039739PubMed 34498509

14. 14

    Nairz M, Haschka D, Dichtl S, et al. (2017). Scientific Reports

    DOI: 10.1038/s41598-017-13046-3

15. 15

    Muller C, Yassin K, Li LS, Palmblad M, Efendic S, Berggren PO, Cerami A, Brines M, Östenson CG. (2016). Molecular Medicine

    DOI: 10.2119/molmed.2015.00267PubMed 26736179

16. 16

    Zhang W, Yu G, Zhang M. (2016). Peptides

    DOI: 10.1016/j.peptides.2015.12.004

17. 17

    Swartjes M, van Velzen M, Niesters M, Aarts L, Brines M, Dunne A, Cerami A, Dahan A. (2014). Molecular Pain

    DOI: 10.1186/1744-8069-10-13PubMed 24529189

18. 18

    Collino M, Benetti E, Rogazzo M, Chiazza F, Mastrocola R, Nigro D, Cutrin JC, Aragno M, Fantozzi R, Minetto MA, Thiemermann C. (2014). British Journal of Pharmacology

    DOI: 10.1111/bph.12888PubMed 25164531

19. 19

    Ahmet I, Tae HJ, Brines M, Cerami A, Lakatta EG, Talan MI. (2013). Journal of Pharmacology and Experimental Therapeutics

    DOI: 10.1124/jpet.113.202945PubMed 23584743

20. 20

    van Rijt WG, Nieuwenhuijs-Moeke GJ, van Goor H, Jespersen B, Ottens PJ, Ploeg RJ, Leuvenink HGD. (2013). Journal of Translational Medicine

    DOI: 10.1186/1479-5876-11-9PubMed 23302512

21. 21

    van Rijt WG, et al. (2013). Journal of Translational Medicine

    PubMed 24225194

22. 22

    Bohr S, Patel SJ, Shen K, Vitalo AG, Brines M, Cerami A, Berthiaume F, Yarmush ML. (2013). PNAS

    DOI: 10.1073/pnas.1214099110PubMed 23401545

23. 23

    Patel NSA, Nandra KK, Brines M, Collino M, Wong WF, Kapoor A, et al. (2011). Molecular Medicine

    DOI: 10.2119/molmed.2011.00053PubMed 21607293

24. 24

    Swartjes M, Morariu A, Niesters M, Brines M, Cerami A, Aarts L, Dahan A. (2011). Anesthesiology

    DOI: 10.1097/ALN.0b013e31822fcefdPubMed 21873879

25. 25

    Ueba H, Brines M, Yamin M, Umemoto T, Ako J, Momomura S, Cerami A, Kawakami M. (2010). PNAS

    DOI: 10.1073/pnas.1003019107PubMed 20660739

26. 26

    Brines M, Patel NSA, Villa P, Brines C, Mennini T, De Paola M, et al. (2008). PNAS

    DOI: 10.1073/pnas.0805594105PubMed 18676614

27. 27

    Brines M, Grasso G, Fiordaliso F, Sfacteria A, Ghezzi P, Fratelli M, Latini R, Xie QW, Smart J, Su-Rick CJ, Pobre E, Diaz D, Gomez D, Hand C, Coleman T, Cerami A. (2004). PNAS

    DOI: 10.1073/pnas.0406491101PubMed 15456912

Related compounds

• B7-33
• Cartalax + BPC-157 + TB-500 + KPV
• Gonadorelin
• Kisspeptin-10