New rad51 inhibitors to target homologous recombination in human cells

Irina S. Shkundina, Alexander A. Gall, Alexej Dick, Simon Cocklin, Alexander V. Mazin

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Targeting DNA repair proteins with small-molecule inhibitors became a proven anti-cancer strategy. Previously, we identified an inhibitor of a major protein of homologous recombination (HR) RAD51, named B02. B02 inhibited HR in human cells and sensitized them to chemotherapeutic drugs in vitro and in vivo. Here, using a medicinal chemistry approach, we aimed to improve the potency of B02. We identified the B02 analog, B02-isomer, which inhibits HR in human cells with significantly higher efficiency. We also show that B02-iso sensitizes triple-negative breast cancer MDA-MB-231 cells to the PARP inhibitor (PARPi) olaparib.

Original languageEnglish (US)
Article number920
JournalGenes
Volume12
Issue number6
DOIs
StatePublished - Jun 2021

Keywords

  • DNA repair
  • Homologous recombination
  • Small-molecule inhibitors
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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