Synthesis and Anti-Tumor Evaluation of Carboranyl BMS-202 Analogues-A Case of Carborane Not as Phenyl Ring Mimetic.

ABSTRACT: Carborane is considered a three-dimensional mimetic of phenyl rings in medicinal chemistry. BMS-202 is a potent PD-L1 inhibitor that can block the PD-L1/PD-1 interaction and restore the immune response to cancer cells. Herein, we replaced the terminal phenyl group of BMS-202 with carborane and prepared its carboranyl BMS-202 analogues. The results showed a loss of PD-L1 binding affinity due to the bulky size of carborane, suggesting that carborane cannot serve as a phenyl ring mimetic in certain cases. Docking study demonstrated that the narrow binding pocket of PD-L1 could not hold the bulky carborane, resulting in loss of its activity. Compounds 1a and 1b exhibited anti-proliferative activities on a broad scope of cancer cell lines. Further studies indicate that compound

SUBMITTER: Yuan C 

PROVIDER: S-EPMC12735689 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature