New RAD51 Inhibitors to Target Homologous Recombination in Human Cells

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 and . Here, us...

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Bibliographic Details
Published in:Genes 2021-06, Vol.12 (6), p.920
Main Authors: Shkundina, Irina S, Gall, Alexander A, Dick, Alexej, Cocklin, Simon, Mazin, Alexander V
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
AIDS
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Binding Sites
Breast cancer
Cancer therapies
Cell Line, Tumor
Cell Proliferation - drug effects
Chemotherapy
DNA repair
Drug Synergism
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
HIV
Homologous recombination
Homologous Recombination - drug effects
Human immunodeficiency virus
Humans
Ligands
Medical prognosis
Molecular Docking Simulation
Penicillin
Phthalazines - pharmacology
Piperazines - pharmacology
Poly(ADP-ribose) polymerase
Protein Binding
Proteins
Quinazolinones - chemistry
Quinazolinones - pharmacology
Rad51 Recombinase - antagonists & inhibitors
Rad51 Recombinase - chemistry
Rad51 Recombinase - metabolism
Radiation therapy
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Summary: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 and . 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.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes12060920