Article ID Journal Published Year Pages File Type
10593076 Bioorganic & Medicinal Chemistry Letters 2012 6 Pages PDF
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 (IC50 = 8 nM) and good cellular activity (EC50 = 310 nM). This provides further evidence that non-ATP-competitive binding MK2 inhibitors are feasible by targeting the outside ATP pocket.
Related Topics
Physical Sciences and Engineering Chemistry Organic Chemistry
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