XJB-5-131

XJB-5-131
Legal status
Legal status	experimental;
Identifiers
CAS Number	866404-31-1;
PubChem CID	11693686;
ChemSpider	9868412;
ChEBI	CHEBI:173099;
Chemical and physical data
Formula	C53H80N7O9
Molar mass	959.263 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES 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 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.^[1]

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.^[1] Therefore XJB-5-131 is seen to reduce oxidative damage to mitochondrial DNA, and to maintain mitochondrial DNA copy number.^[2] XJB-5-131 also strongly protects against ferroptosis, a form of iron-dependent regulated cell death.^[3]

References

^ ^a ^b 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.
^ 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.
^ 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.

References

Further reading