1. Discovery of a novel class of triazolones as Checkpoint Kinase inhibitors—Hit to lead exploration
- Author
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Paul Lyne, Patrick Brassil, Ann White, Jason Breed, Mei Su, Dorin Toader, Yan Yu, Sonya Zabludoff, Jon Read, James W. Janetka, Chun Deng, Dingwei Yu, Vibha Oza, Susan Ashwell, Zheng Xiaolan, Nicholas John Newcombe, Candice Horn, Martin Pass, Peter J. H. Webborn, Ludo Otterbien, Heather Haye, Jay Ezhuthachan, Anna L Valentine, and Sian Roswell
- Subjects
Models, Molecular ,animal structures ,High-throughput screening ,genetic processes ,Clinical Biochemistry ,Pharmaceutical Science ,Computational biology ,Crystallography, X-Ray ,environment and public health ,Biochemistry ,Structure-Activity Relationship ,Drug Discovery ,Structure–activity relationship ,CHEK1 ,Protein kinase A ,Protein Kinase Inhibitors ,Molecular Biology ,Kinase ,Drug discovery ,Chemistry ,Organic Chemistry ,Hit to lead ,Triazoles ,enzymes and coenzymes (carbohydrates) ,Checkpoint Kinase 1 ,Molecular Medicine ,biological phenomena, cell phenomena, and immunity ,Signal transduction ,Protein Kinases - Abstract
Checkpoint Kinase-1 (Chk1, CHK1, CHEK1) is a Ser/Thr protein kinase that mediates cellular responses to DNA-damage. A novel class of Chk1 inhibitors, triazoloquinolones/triazolones (TZ's) was identified by high throughput screening. The optimization of these hits to provide a lead series is described.
- Published
- 2010