Therapeutic disruption of RAD52-ssDNA complexation via novel drug-like inhibitors.

ABSTRACT: RAD52 protein is a coveted target for anticancer drug discovery. Similar to poly-ADP-ribose polymerase (PARP) inhibitors, pharmacological inhibition of RAD52 is synthetically lethal with defects in genome caretakers BRCA1 and BRCA2 (∼25% of breast and ovarian cancers). Emerging structure activity relationships for RAD52 are complex, making it challenging to transform previously identified disruptors of the RAD52-ssDNA interaction into drug-like leads using traditional medicinal chemistry approaches. Using pharmacophoric informatics on the RAD52 complexation by epigallocatechin (EGC), and the Enamine in silico REAL database, we identified six distinct chemical scaffolds that occupy the same physical space on RAD52 as EGC. All six were RAD52 inhibitors (IC₅₀ ∼23-1200 μM) wi

SUBMITTER: Bhat DS 

PROVIDER: S-EPMC10150327 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature