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Novel Small Molecule Inhibitor for Treatment of PARP Inhibitor-resistant Ovarian Cancer
Yale University
Small molecule
Oncology
Hit To Lead or Lead Optimization
• HR repair and sensitized HR repair proficient EOC to PARP inhibitors.
• Poly ADP-ribose polymerase (PARP) inhibitors are promising targeted therapy for epithelial ovarian cancer (EOC) with BRCA mutations or defective homologous recombination (HR) repair. However, reversion of BRCA mutation and restoration of HR repair in EOC lead to PARP inhibitor resistance and reduced clinical efficacy of PARP inhibitors.
• Triapine, a small molecule inhibitor of ribonucleotide reductase (RNR), impaired HR repair and sensitized HR repair proficient EOC to PARP inhibitors.
• The discovery of a putative small molecule inhibitor of RNR and HR repair for combination with PARP inhibitors to treat PARP inhibitor-resistant and HR repair-proficient EOC.
WO2022221181A1
In silico screening identifies a novel small molecule inhibitor that counteracts PARP inhibitor resistance in ovarian cancer, Sci Rep.
(2021)