1. Discovery and Optimization of Highly Selective Inhibitors of CDK5
- Author
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Matthew H. Daniels, Goran Malojcic, Susan L. Clugston, Brett Williams, Marie Coeffet-Le Gal, Xin-Ru Pan-Zhou, Srinivasan Venkatachalan, Jean-Christophe Harmange, and Mark Ledeboer
- Subjects
Models, Molecular ,Structure-Activity Relationship ,HEK293 Cells ,Drug Design ,Drug Discovery ,Humans ,Molecular Medicine ,Cyclin-Dependent Kinase 5 ,Polycystic Kidney, Autosomal Dominant ,Protein Kinase Inhibitors ,Cyclin-Dependent Kinases ,Cell Proliferation ,Substrate Specificity - Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent monogenic human disease, but to date, only one therapy (tolvaptan) is approved to treat kidney cysts in ADPKD patients. Cyclin-dependent kinase 5 (CDK5), an atypical member of the cyclin-dependent kinase family, has been implicated as a target for treating ADPKD. However, no compounds have been disclosed to date that selectively inhibit CDK5 while sparing the broader CDK family members. Herein, we report the discovery of CDK5 inhibitors, including
- Published
- 2022