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August 6, 2026Journal of Medicinal Chemistry

Discovery, Synthesis,and Biological Evaluation of1,3,4,5-Tetrahydro-6 H -pyrano4,3- c isoquinolin-6-one Derivatives as Novel and Highly SelectivePARP1 Inhibitors

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Authors

ZGZhongning GuoRSRongrong SunLYLinyu Yang

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Overview

Randomized trial evaluates PARP1 inhibitors in BRCA-deficient cells, indicating therapeutic potential for cancer treatment.

Key Points

  • This research aims to develop highly selective PARP1 inhibitors for enhanced cancer therapy.
  • Structure-guided design and optimization of (R)-A17 as a PARP1 inhibitor.
  • Assessment of enzymatic potency and selectivity over PARP2.
  • Evaluation of in vivo antitumor efficacy using BRCA mutant xenograft models.
  • PARP1 inhibitor (R)-A17 shows potent activity with an IC50 of 2.4 nM and 65.8-fold selectivity over PARP2.
  • Demonstrated tumor growth inhibition of 57.8%, 86.3%, and 91.3% at doses of 0.3, 1, and 3 mg/kg, respectively.
  • Achieved complete oral bioavailability (F = 100%) in mice.

Cite This Study

Guo et al. (2026) studied this question.

synapsesocial.com/papers/6a74375e764cddc9499d4b92https://doi.org/10.1021/acs.jmedchem.6c00295
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