Selectivity of Kinase Inhibitor Fragments

被引：58

作者：

Bamborough, Paul ^{[1
]}

Brown, Murray J. ^{[1
]}

Christopher, John A. ^{[1
]}

Chung, Chun-wa ^{[1
]}

Mellor, Geoff W. ^{[1
]}

机构：

[1] GlaxoSmithKline R&D, Med Res Ctr, Stevenage SG1 2NY, Herts, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 14期

关键词：

X-RAY CRYSTALLOGRAPHY; P38 MAP KINASE; DRUG DISCOVERY; LEAD DISCOVERY; TARGET IMMOBILIZATION; LIGAND SPECIFICITY; TYROSINE KINASES; IKK2; INHIBITORS; LIBRARY DESIGN; POTENT;

D O I：

10.1021/jm200349b

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A kinase-focused screening set of fragments has been assembled and has proved successful for the discovery of ligand-efficient hits against many targets. Here we present some of our general conclusions from this exercise. Notably, we present the first profiling results for literature fragments that have previously been used as starting points for optimization against individual kinases. We consider the importance of screening format and the extent to which selectivity is helpful in selecting fragments for progression. Results are also outlined for fragments targeting the DFG-out conformation and for atypical kinases such as PM and lipid kinases.

引用

页码：5131 / 5143

页数：13

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