DCC-2036 (CAS 1020172-07-9)

DCC-2036 is a potent inhibitor against purified native Abl1 in unphosphorylated (u-Abl1native) (IC50 of 0.8 nM) and phosphorylated (p-Abl1native) (IC50 of 2 nM) forms, unphosphorylated (IC50 of 1.4 nM) and phosphorylated (IC50 of 5 nM) gatekeeper mutant Abl1T315I, and the activation loop mutant Abl1H396P (IC50 of 4 nM) in a non-ATP-competitive manner. DCC-2036 inhibits the Src family kinases Src (IC50 of 34 nM), LYN (IC50 of 29 nM), FGR (IC50 of 38 nM), and HCK (IC50 of 40 nM), and the receptor TKs KDR (IC50 of 4 nM), FLT3 (IC50 of 2 nM), and TIE2 (IC50 of 6 nM). DCC-2036 displays anti-proliferative activities against Ba/F3 cells expressing native or mutant Bcr-Abl1 (IC50 ranging from 2 nM to 150 nM). DCC-2036 is an inhibitor of proliferation of the Ph+ cell line K562 (IC50 of 5.5 nM), and induces apoptosis in both Bcr-Abl1-expressing Ba/F3 and K562 cells potently. A recent study shows that DCC-2036 shows the selectivity for growth inhibition of Bcr-Abl-positive cells by its marked inhibition of CML cell lines compared to non-CML leukemia lines.