Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10593076 | Bioorganic & Medicinal Chemistry Letters | 2012 | 6 Pages |
Abstract
A three-step protocol for SAR development was introduced and applied to the SAR studies of the MK2 inhibitor program. Following this protocol, key conformational features and functional groups for improving MK2 inhibitor activity were quickly identified. Through this effort, the initial gap observed between in vitro binding activity and cellular activity in the lead identification stage was very much reduced. Compound 28 was identified with single digit binding activity (IC50Â =Â 8Â nM) and good cellular activity (EC50Â =Â 310Â nM). This provides further evidence that non-ATP-competitive binding MK2 inhibitors are feasible by targeting the outside ATP pocket.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Xianhai Huang, Xiaohong Zhu, Xiao Chen, Wei Zhou, Dong Xiao, Sylvia Degrado, Robert Aslanian, James Fossetta, Daniel Lundell, Fang Tian, Prashant Trivedi, Anandan Palani,