Discovery of 2-arylquinazoline derivatives as a new class of ASK1 inhibitors |
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Authors: | Andrii Monastyrskyi Simon Bayle Victor Quereda Wayne Grant Michael Cameron Derek Duckett William Roush |
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Institution: | 1. Department of Chemistry, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, United States;2. Department of Molecular Medicine, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, United States |
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Abstract: | The development of a new series of apoptosis signal-regulating kinase 1 (ASK1) inhibitors is described. Starting from purine, pyrimidine and quinazoline scaffolds identified by high throughput screening, we used tools of structure-based drug design to develop a series of potent kinase inhibitors, including 2-arylquinazoline derivatives 12 and 23, with submicromolar inhibitory activities against ASK1. Kinetic analysis demonstrated that the 2-arylquinazoline scaffold ASK1 inhibitors described herein are ATP competitive. |
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Keywords: | Apoptosis signal-regulating kinase (ASK1) High throughput screening Structure-based drug design Kinase Inhibitor |
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