XJB-5-131

XJB-5-131
line drawing of XJB-5-131
Legal status
Legal status
  • experimental
Identifiers
CAS Number
PubChem CID
ChemSpider
ChEBI
Chemical and physical data
FormulaC53H80N7O9
Molar mass959.263 g·mol−1
3D model (JSmol)
  • CC(C)CC(C=CC(Cc1ccccc1)C(=O)N2CCCC2C(=O)NC(C(C)C)C(=O)NC(CCCNC(=O)OCc3ccccc3)C(=O)NC4CC(N(C(C4)(C)C)[O])(C)C)NC(=O)OC(C)(C)C
  • InChI=1S/C53H80N7O9/c1-35(2)30-40(56-50(66)69-51(5,6)7)27-26-39(31-37-20-14-12-15-21-37)48(64)59-29-19-25-43(59)46(62)58-44(36(3)4)47(63)57-42(24-18-28-54-49(65)68-34-38-22-16-13-17-23-38)45(61)55-41-32-52(8,9)60(67)53(10,11)33-41/h12-17,20-23,26-27,35-36,39-44H,18-19,24-25,28-34H2,1-11H3,(H,54,65)(H,55,61)(H,56,66)(H,57,63)(H,58,62)/b27-26+/t39-,40-,42+,43+,44+/m1/s1
  • Key:VDQKIDYOPUMJGQ-VQPCLXHQSA-N

XJB-5-131 is a mitochondria-targeted synthetic nitroxide antioxidant. The molecule is composed of two parts: a peptide isostere delivery component. Peptide was drawn from the cyclopeptide antibiotic gramicidin S, that targets the inner mitochondrial membrane. And the second part is a 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) nitroxide radical scavenger that disregards any oxygen species that are reactive.

In a mouse model of Huntington's disease, XJB-5-131 has been seen to suppress somatic CAG repeat expansion by disturbing the toxic oxidation cycle. This process uses excision repair and mismatch repair pathway to promote oxidative DNA damage. Therefore XJB-5-131 is seen to reduce oxidative damage to mitochondrial DNA, and to maintain mitochondrial DNA copy number. XJB-5-131 also strongly protects against ferroptosis, a form of iron-dependent regulated cell death.

References

  1. 1 2 Wipf P, Polyzos AA, McMurray CT. "XJB-5-131 is a suppressor of somatic instability and toxicity in Huntington's disease." Journal of Huntington's Disease. 2022; Pre-press December 2021.
  2. ↑ Xun Z, Rivera-Sánchez S, Ayala-Peña S, Lim J, Budworth H, Skoda EM, et al. (November 2012). "Targeting of XJB-5-131 to mitochondria suppresses oxidative DNA damage and motor decline in a mouse model of Huntington's disease". Cell Reports. 2 (5): 1137–42. doi:10.1016/j.celrep.2012.10.001. PMC 3513647. PMID 23122961.
  3. ↑ Krainz T, Gaschler MM, Lim C, Sacher JR, Stockwell BR, Wipf P (September 2016). "A Mitochondrial-Targeted Nitroxide Is a Potent Inhibitor of Ferroptosis". ACS Central Science. 2 (9): 653–659. doi:10.1021/acscentsci.6b00199. PMC 5043442. PMID 27725964.

Further reading

Sun W, Lv Z, Li W, et al. "XJB-5-131 protects chondrocytes from ferroptosis to alleviate osteoarthritis progression via restoring Pebp1 expression." Journal of Orthopaedic Translation. 2024;44:114–124