产品描述:
GMB 475 is a proteolysis-targeting chimera (PROTAC) containing the Bcr-Abl inhibitor GNF-5 (Item No. 16254) conjugated to VHL ligand 1 (Item No. 21591).{49846} It induces degradation of Bcr-Abl with a half-maximal degradation concentration (DC50) value of 340 nM. GMB 475 selectively inhibits the proliferation of K562 chronic myeloid leukemia (CML) and Bcr-Abl-expressing Ba/F3 cells (IC50 = ~1 µM for both) over parental Ba/F3 cells (IC50 = >10 µM). It also inhibits the proliferation of Ba/F3 cells expressing mutant Bcr-Abl (IC50s = 1.98 and 0.37 µM for Bcr-AblT315I and Bcr-AblG250E, respectively). GMB 475 (2.5 µM) induces apoptosis in primary human CML cells.