Discovery of ZN-c3, a Highly Potent and Selective Wee1 Inhibitor Undergoing Evaluation in Clinical Trials for the Treatment of Cancer

  • J Med Chem. 2021 Sep 9;64(17):13004-13024. doi: 10.1021/acs.jmedchem.1c01121.
Peter Q Huang  1 ,  Brant C Boren  1 ,  Sayee G Hegde  1 ,  Hui Liu  1 ,  Aditya K Unni  1 ,  Sunny Abraham  1 ,  Chad D Hopkins  1 ,  Sunil Paliwal  1 ,  Ahmed A Samatar  1 ,  Jiali Li  1 ,  Kevin D Bunker  1
Affiliations
  • 1. Zentalis Pharmaceuticals, San Diego, California 92121, United States.
PMID: 34423975 DOI: 10.1021/acs.jmedchem.1c01121
Abstract

Wee1 inhibition has received great attention in the past decade as a promising therapy for Cancer treatment. Therefore, a potent and selective Wee1 Inhibitor is highly desirable. Our efforts to make safer and more efficacious Wee1 inhibitors led to the discovery of compound 16, a highly selective Wee1 Inhibitor with balanced potency, ADME, and pharmacokinetic properties. The chiral ethyl moiety of compound 16 provided an unexpected improvement of Wee1 potency. Compound 16, known as ZN-c3, showed excellent in vivo efficacy and is currently being evaluated in phase 2 clinical trials.

Products