Discovery of small-molecule inhibitors of RUVBL1/2 ATPase.

ABSTRACT: RUVBL1 and RUVBL2 are highly conserved AAA ATPases (ATPases Associated with various cellular Activities) and highly relevant to the progression of cancer, which makes them attractive targets for novel therapeutic anticancer drugs. In this work, docking-based virtual screening was performed to identify compounds with activity against the RUVBL1/2 complex. Seven compounds showed inhibitory activity against the complex in both enzymatic and cellular assays. A series of pyrazolo[1,5-a]pyrimidine-3-carboxamide analogs were synthesized based on the scaffold of compound 15 with inhibitory activity and good potential for structural manipulation. Analysis of the structure-activity relationship identified the benzyl group on R₂ and aromatic ring-substituted piperazinyl on R₄ as

SUBMITTER: Zhang G 

PROVIDER: S-EPMC9034851 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature