title: Discovery of potent LPA2 (EDG4) antagonists as potential anticancer agents.
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.
authors.affiliation: Chemistry Research & Discovery, Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. hbeck@amgen.com
authors.forename: Hilary P
authors.initials: HP
authors.lastname: Beck
authors.forename: Todd
authors.initials: T
authors.lastname: Kohn
authors.forename: Steven
authors.initials: S
authors.lastname: Rubenstein
authors.forename: Christine
authors.initials: C
authors.lastname: Hedberg
authors.forename: Ralf
authors.initials: R
authors.lastname: Schwandner
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hasslinger
authors.forename: Kang
authors.initials: K
authors.lastname: Dai
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.forename: Lingming
authors.initials: L
authors.lastname: Liang
authors.forename: Holger
authors.initials: H
authors.lastname: Wesche
authors.forename: Brendon
authors.initials: B
authors.lastname: Frank
authors.forename: Songhzu
authors.initials: S
authors.lastname: An
authors.forename: Dineli
authors.initials: D
authors.lastname: Wickramasinghe
authors.forename: Juan
authors.initials: J
authors.lastname: Jaen
authors.forename: Julio
authors.initials: J
authors.lastname: Medina
authors.forename: Randall
authors.initials: R
authors.lastname: Hungate
authors.forename: Wang
authors.initials: W
authors.lastname: Shen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D049368:Receptors, Lysophosphatidic Acid; D048049:Extracellular Signal-Regulated MAP Kinases