Abstract
A novel 5-phenylamino-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione series of MEK inhibitors has been developed using structure-based drug design. Lead optimization of this series led to the discovery of TAK-733. This was advanced to Phase I clinical studies for cancer treatment.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Binding Sites
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Crystallography, X-Ray
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Drug Discovery*
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Humans
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MAP Kinase Kinase Kinases / antagonists & inhibitors*
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Models, Molecular
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Molecular Structure
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Neoplasms / drug therapy*
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Pyridones / chemical synthesis
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Pyridones / chemistry
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Pyridones / therapeutic use*
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Pyrimidinones / chemical synthesis
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Pyrimidinones / chemistry
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Pyrimidinones / therapeutic use*
Substances
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Antineoplastic Agents
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Pyridones
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Pyrimidinones
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TAK 733
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MAP Kinase Kinase Kinases