Abstract
The LPA(2) protein is overexpressed in many tumor cells. We report the optimization of a series of LPA(2) antagonists using calcium mobilization assay (aequorin assay) that led to the discovery of the first reported inhibitors selective for LPA(2). Key compounds were evaluated in vitro for inhibition of LPA(2) mediated Erk activation and proliferation of HCT-116 cells. These compounds could be used to evaluate the benefits of LPA(2) inhibition both in vitro and in vivo.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Combinatorial Chemistry Techniques*
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Dose-Response Relationship, Drug
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Drug Design
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Humans
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Molecular Structure
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Receptors, Lysophosphatidic Acid / antagonists & inhibitors*
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Receptors, Lysophosphatidic Acid
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Extracellular Signal-Regulated MAP Kinases