Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase

被引：564

作者：

Pan, Zhengying

Scheerens, Heleen

Li, Shyr-Jiann

Schultz, Brian E.

Sprengeler, Paul A.

Burrill, L. Chuck

Mendonca, Rohan V.

Sweeney, Michael D.

Scott, Keana C. K.

Grothaus, Paul G.

Jeffery, Douglas A.

Spoerke, Jill M.

Honigberg, Lee A.

Young, Peter R.

Dalrymple, Stacie A.

Palmer, James T.

机构：

[1] Department of Medicinal Chemistry, Celera Genomics, South San Francisco, CA 94080

[2] Department of Biology, Celera Genomics, South San Francisco, CA 94080

[3] Informatics, Computational Science Group, Celera Genomics, Rockville, MD 20850

来源：

CHEMMEDCHEM | 2007年 / 2卷 / 01期

关键词：

Biological activity; Drug design; Enzymes; Medicinal chemistry; Structural bioinformatics;

D O I：

10.1002/cmdc.200600221

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

(Chemical Equation Presented) A series of highly selective irreversible inhibitors for Bruton's tyrosine kinase (Btk) was developed using a structural bioinformatics approach. Their capabilities to modulate Btk's activity were characterized both in vitro and in vivo. Oral treatment with once-a-day dosing of compound 4 greatly inhibited disease development in a rodent rheumatoid arthritis (RA) model.

引用

页码：58 / 61

页数：4

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