BCR-ABL-IN-2

BCR-ABL-IN-2 is an inhibitor of BCR-ABL1 tyrosine kinase, with IC₅₀s of 57 nM, 773 nm for ABL1^native and ABL1^T315I, respectively. IC50 & Target: IC50: 57 nM (ABL1^native), 773 nM (ABL1^T315I)^[1]. In Vitro: BCR-ABL-IN-2 (Compound 1) contains a urea moiety to allow a hydrogen bond with the conserved K271-E286 salt bridge of ABL1, a t-butyl moiety to bind into the hydrophobic spine at the third pocket position, and a 2,3-dichlorophenyl ring to stabilize the DFG-phenylalanine F382 in the Type II-out conformation. BCR-ABL-IN-2 exhibits an IC₅₀ of 57 nM for ABL1^native and an IC₅₀ of 773 nM for ABL1^T315I[1]. Despite ABL, BCR-ABL-IN-2 can also inhibit KDR, BRaf, p38 kinase with IC₅₀s of 1.8 μM, 0.23 μM, 6.3 nM, 43 nM, respectively^[2].