GMB475

• CAT Number: I028167
• CAS Number: 2490599-18-1
• Molecular Formula: C43H46F3N7O7S
• Molecular Weight: 861.94
• Purity: 98%
• Solubility: Soluble in DMSO
• Storage: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
• IUPAC Name: (2S)-1-((R)-3,3-dimethyl-2-(2-(2-(4-(6-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-4-yl)phenoxy)ethoxy)acetamido)butanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide
• InChI: 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-/m0/s1
• InChIKey: ONDVWISBMHHLGZ-CQQKSQRMSA-N
• SMILES: FC(F)(F)OC1=CC=C(NC2=CC(C3=CC=C(OCCOCC(N[C@H](C(C)(C)C)C(N4[C@H](C(NCC5=CC=C(C6=C(C)N=CS6)C=C5)=O)CC(O)C4)=O)=O)C=C3)=NC=N2)C=C1

GMB-475（Cat No.:I028167） is a compound that functions as a degrader of BCR-ABL1 tyrosine kinase, utilizing the PROTAC (proteolysis-targeting chimera) approach. It effectively addresses drug resistance associated with BCR-ABL1-dependent malignancies. GMB-475 selectively targets the BCR-ABL1 protein and recruits the E3 ligase Von Hippel Lindau (VHL), leading to ubiquitination and subsequent degradation of the oncogenic fusion protein. In studies, GMB-475 demonstrated a reduction in viability and increased apoptosis in primary chronic myeloid leukemia (CML) CD34+ cells, while exhibiting no significant effects on healthy CD34+ cells at the same concentrations.

Reference

1: Burslem GM, Schultz AR, Bondeson DP, Eide CA, Savage Stevens SL, Druker BJ, Crews CM. Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation. Cancer Res. 2019 Sep 15;79(18):4744-4753. doi: 10.1158/0008-5472.CAN-19-1236. Epub 2019 Jul 16. PubMed PMID: 31311809; PubMed Central PMCID: PMC6893872.