| Abstract
| - It has been reported that the diaryl urea class of p38α inhibitors binds to p38 map kinasewith both high affinity and slow binding kinetics (Pargellis et al. Nat. Struct. Biol.2002, 9,268−272). The slow binding kinetics of this class of inhibitors is believed to be the result ofbinding to an allosteric pocket adjacent to the p38α active site. The use of traditional kineticand equilibrium methods to measure the binding affinity of this class of compounds has createdmany challenges for determination of structure-activity relationships (SAR). The thermaldenaturation method provides a means of measuring high-affinity interactions. In this paper,the method of thermal denaturation will be described as it has been applied to the diaryl ureaclass of p38 map kinase inhibitors.
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