Abstract
Fragment-based hit identification coupled with crystallographically enabled structure-based drug design was used to design potent inhibitors of JAK-2. After two iterations from fragment 1, we were able to increase potency by greater than 500-fold to provide sulfonamide 13, a 78-nM JAK-2 inhibitor.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Crystallography, X-Ray
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Drug Design
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Drug Discovery / methods*
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Humans
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Janus Kinase 2 / antagonists & inhibitors*
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Janus Kinase 2 / chemistry
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Models, Molecular
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Protein Kinase Inhibitors / chemistry*
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Small Molecule Libraries*
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Structure-Activity Relationship
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Sulfonamides / chemistry
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Sulfonamides / pharmacology
Substances
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Protein Kinase Inhibitors
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Small Molecule Libraries
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Sulfonamides
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Janus Kinase 2