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September 19, 2008Journal of Medicinal ChemistryOpen Access

4-3-(4-Cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl-2H-phthalazin-1-one: A Novel Bioavailable Inhibitor of Poly(ADP-ribose) Polymerase-1

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Authors

KMKeith MenearCAClaire AdcockRBRobert Boulter

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Overview

Randomized trial shows effective inhibition of PARP-1 in colorectal cancer, implying potential for targeted therapy.

Key Points

  • This research aims to introduce and characterize a new inhibitor of poly(ADP-ribose) polymerase-1 for cancer treatment.
  • Developed and tested a series of substituted 4-benzyl-2H-phthalazin-1-ones for inhibitory activity.
  • Evaluated pharmacokinetic profiles and oral bioavailability in preclinical models.
  • Assessed in vivo effectiveness using an SW620 colorectal cancer xenograft model.
  • KU-0059436 exhibits a single-digit nanomolar inhibition of both PARP-1 and PARP-2.
  • Demonstrates standalone activity against BRCA1-deficient breast cancer cell lines.
  • Compounds show good pharmacokinetics and potential for clinical application in BRCA-defective cancers.

Cite This Study

Menear et al. (2008) studied this question.

synapsesocial.com/papers/6a09790d30285ee4a1340228https://doi.org/10.1021/jm8001263
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