DCC-2036 (Rebastinib) is a highly potent, non-ATP-competitive BCR-ABL1 inhibitor with IC50 of 0.8 and 4 nM for native ABL1 and gatekeeper mutant ABL1 T315I, respectively.
DCC-2036 also inhibits the SRC family kinases SRC, LYN, FGR, and HCK, and the receptor TKs KDR, FLT3, and TIE2 (IC50s=2-40 nM), but spares c-KIT (IC50=480 nM).
DCC-2036 potently inhibits unphosphorylated and phosphorylated of ABL1 native with IC50 of 0.75 and 2 nM, potently inhibits unphosphorylated and phosphorylated of ABL1 T315I with IC50 of 5 and 4 nM, also potently inhibits ABL1 H396P (IC50=1.4 nM).
DCC-2036 inhibits cellular proliferation of Ba/F3 cells expressing native or T315I mutant with IC50 of 5.4 and 13 nM, also inhibits proliferation of several common TKI-resistant mutants of BCR-ABL1, including G250E, Q252H, Y235F, E255K, V299L, F317L, and M351T with IC50 of 6-150 nM.
DCC-2036 prolongs survival in mouse Ba/F3 cell allograft models.