Daniel K. Treiber

TL;DR: This work presents interaction maps for 38 kinase inhibitors across a panel of 317 kinases representing >50% of the predicted human protein kinome and introduces the concept of a selectivity score as a general tool to quantify and differentiate the observed interaction patterns.

TL;DR: An efficient way to determine kinase inhibitor specificity by measuring binding of small molecules to the ATP site of kinases is described, which represents a systematic small molecule-protein interaction map for clinical compounds across a large number of related proteins.

TL;DR: The avoidance of the innermost cavity of the Abl kinase domain by VX-680 and the specific recognition of the active conformation explain the effectiveness of this compound against mutant forms of BCR-Abl, including those with mutations at the gatekeeper position.

TL;DR: The approach described enables investigation of the complex relationship between kinase activation state and compound binding affinity and should facilitate strategic inhibitor design.

TL;DR: A series of diaryl ureas with an amide substitution at the 4-position was prepared and found to be potent and selective FLT3 inhibitors with good oral bioavailability and efficacy in a tumor xenograft model.