Discovery of potent LPA2 (EDG4) antagonists as potential anticancer agents

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 inhibitio...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2008-02, Vol.18 (3), p.1037-1041
Main Authors: BECK, Hilary P, KOHN, Todd, FRANK, Brendon, AN, Songhzu, WICKRAMASINGHE, Dineli, JAEN, Juan, MEDINA, Julio, HUNGATE, Randall, WANG SHEN, RUBENSTEIN, Steven, HEDBERG, Christine, SCHWANDNER, Ralf, HASSLINGER, Kerstin, KANG DAI, CONG LI, LINGMING LIANG, WESCHE, Holger
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Biological and medical sciences
Combinatorial Chemistry Techniques
Dose-Response Relationship, Drug
Drug Design
Extracellular Signal-Regulated MAP Kinases - metabolism
General aspects
Humans
Medical sciences
Molecular Structure
Pharmacology. Drug treatments
Receptors, Lysophosphatidic Acid - antagonists & inhibitors
Tumor Cells, Cultured
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Summary: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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2007.12.024