GMB 475

GMB 475 is a proteolysis-targeting chimera (PROTAC) containing the Bcr-Abl inhibitor GNF-5 (Cay-16254) conjugated to VHL ligand 1 (Cay-21591). 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.Formal Name: (4R)-3-methyl-N-[2-[2-[4-[6-[[4-(trifluoromethoxy)phenyl]amino]-4-pyrimidinyl]phenoxy]ethoxy]acetyl]-L-valyl-4-hydroxy-N-[[4-(4-methyl-5-thiazolyl)phenyl]methyl]-L-prolinamide. CAS Number: 2490599-18-1. Molecular Formula: C43H46F3N7O7S. Formula Weight: 861.9. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Soluble: >10 mg/ml, Ethanol: Sparingly Soluble: 1-10 mg/ml. SMILES: O=C(N(C[C@@H]1O)[C@@H](C1)C(NCC2=CC=C(C(SC=N3)=C3C)C=C2)=O)[C@H](C(C)(C)C)NC(COCCOC4=CC=C(C5=NC=NC(NC(C=C6)=CC=C6OC(F)(F)F)=C5)C=C4)=O. InChi Code: InChI=1S/C43H46F3N7O7S/c1-26-38(61-25-50-26)29-7-5-27(6-8-29)21-47-40(56)35-19-31(54)22-53(35)41(57)39(42(2,3)4)52-37(55)23-58-17-18-59-32-13-9-28(10-14-32)34-20-36(49-24-48-34)51-30-11-15-33(16-12-30)60-43(44,45)46/h5-16,20,24-25,31,35,39,54H,17-19,21-23H2,1-4H3,(H,47,56)(H,52,55)(H,48,49,51)/t31-,35+,39-/m1/s1. InChi Key: ONDVWISBMHHLGZ-SBJIGXGQSA-N.