New rad51 inhibitors to target homologous recombination in human cells

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

doi:10.3390/genes12060920

New rad51 inhibitors to target homologous recombination in human cells

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

Department of Biochemistry & Structural Biology

Research output: Contribution to journal › Article › peer-review

32 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 language	English (US)
Article number	920
Journal	Genes
Volume	12
Issue number	6
DOIs	https://doi.org/10.3390/genes12060920
State	Published - 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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10.3390/genes12060920

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title = "New rad51 inhibitors to target homologous recombination in human cells",

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.",

keywords = "DNA repair, Homologous recombination, Small-molecule inhibitors, Triple-negative breast cancer",

author = "Shkundina, {Irina S.} and Gall, {Alexander A.} and Alexej Dick and Simon Cocklin and Mazin, {Alexander V.}",

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AU - Shkundina, Irina S.

AU - Gall, Alexander A.

AU - Dick, Alexej

AU - Cocklin, Simon

AU - Mazin, Alexander V.

PY - 2021/6

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AB - 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.

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KW - Homologous recombination

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New rad51 inhibitors to target homologous recombination in human cells

Abstract

Keywords

ASJC Scopus subject areas

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