Hsp90 inhibitor 5b

Hsp90 inhibitor 5b is a first-in-class, small molecule inhibitor of the C-terminal (CTD) Hsp90 dimerization with KD of 3.42 uM, IC50 of 1.3 uM against leukemia cell line K562.Hsp90 inhibitor 5b inhibits Hsp90 chaperone function, does not show any interaction with the NTD of Hsp90.Hsp90 inhibitor 5b down-regulated the phospho-BCR-ABL1 and total-BCR-ABL1 levels, as well as the related downstream signaling pathways, additionally reduced the expression of client proteins associated with Hsp90 chaperone activity, involving Akt, Stat5, and c-Myc.Hsp90 inhibitor 5b inhibited leukemic cell lines (K562, KCL22 and HL60) proliferation and induced apoptosis in a caspase 3/7 enzyme-dependent assay.Hsp90 inhibitor 5b is effective against resistant leukemia cells and in the zebrafish xenotransplantation model.

1. Sanil Bhatia, et al. ChemRxiv