User:RelentlessRecusant/BMS-354825

BMS-354825, IUPAC name N-(2-Chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide, is a small-molecule chemical inhibitor of the oncogenic BCR-ABL fusion kinase (Breakpoint cluster region-Abelson kinase) and of Src family kinases (Src, Lck, and Yes). BMS-354825 has an IC50 < 1.0 nM against BCR-ABL, IC50 = 0.40 nM against Lck, and IC50 = 0.50 nM against Src and Yes.

It is a highly potent of both BCR-ABL and Src kinases in sub-nanomolar concentrations, and serves as a polypharmacological dual inhibitor, thus relaxing its structural binding specificity to ABL and increasing tolerance to point amino acid mutations that would otherwise confer resistance to other kinase inhibitors; BMS-354825's characteristics allow it to override the M244V, G250E, Q252H, Q252R, Y253F, Y253H, E255K, E255V, F317L, M351T, E355G, F359V, H396R, and F486S mutations in ABL that otherwise confer resistance to imantinib, thus demonstrating its clinical relevance.