Abstract
As part of a program to develop a small molecule inhibitor of LIMK, a series of aminothiazole inhibitors were discovered by high throughput screening. Scaffold hopping and subsequent SAR directed development led to a series of low nanomolar inhibitors of LIMK1 and LIMK2 that also inhibited the direct biomarker p-cofilin in cells and inhibited the invasion of MDA MB-231-luc cells in a matrigel inverse invasion assay.
MeSH terms
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Actin Depolymerizing Factors / metabolism
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Animals
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Biotransformation
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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High-Throughput Screening Assays
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Humans
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Lim Kinases / antagonists & inhibitors*
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Microsomes, Liver / metabolism
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Neoplasm Invasiveness
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Structure-Activity Relationship
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Thiazoles / chemical synthesis*
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Thiazoles / pharmacology*
Substances
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Actin Depolymerizing Factors
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Enzyme Inhibitors
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Thiazoles
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LIMK1 protein, human
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LIMK2 protein, human
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Lim Kinases