Discovery of highly potent, selective, covalent inhibitors of JAK3

[Display omitted] A useful and novel set of tool molecules have been identified which bind irreversibly to the JAK3 active site cysteine residue. The design was based on crystal structure information and a comparative study of several electrophilic warheads.

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 27; no. 20; pp. 4622 - 4625
Main Authors:	Kempson, James, Ovalle, Damaso, Guo, Junqing, Wrobleski, Stephen T., Lin, Shuqun, Spergel, Steven H., Duan, James J.-W., Jiang, Bin, Lu, Zhonghui, Das, Jagabandhu, Yang, Bingwei V., Hynes, John, Wu, Hong, Tokarski, John, Sack, John S., Khan, Javed, Schieven, Gary, Blatt, Yuval, Chaudhry, Charu, Salter-Cid, Luisa M., Fura, Aberra, Barrish, Joel C., Carter, Percy H., Pitts, William J.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 15-10-2017 Elsevier
Subjects:	60 APPLIED LIFE SCIENCES Binding Sites Catalytic Domain Cell Line Cell Survival - drug effects Covalent Drug Evaluation, Preclinical Humans Inhibitory Concentration 50 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY Irreversible inhibitor JAK3 Janus Kinase 1 - antagonists & inhibitors Janus Kinase 1 - metabolism Janus Kinase 2 - antagonists & inhibitors Janus Kinase 2 - metabolism Janus Kinase 3 - antagonists & inhibitors Janus Kinase 3 - metabolism Molecular Docking Simulation Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - metabolism Protein Kinase Inhibitors - pharmacology Structure-Activity Relationship Covalent JAK3 Irreversible inhibitor
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Description
Summary:	[Display omitted] A useful and novel set of tool molecules have been identified which bind irreversibly to the JAK3 active site cysteine residue. The design was based on crystal structure information and a comparative study of several electrophilic warheads.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 INDUSTRY
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2017.09.023