Dr. Lynch and colleagues have used classical medicinal chemistry to generate a library of LPA structural analogs. In testing these novel chemical entities as cloned receptors and as substrates for the LPA ecto-phosphatases, the investigators identified compounds that are stable, receptor subtype-selective agonists and inhibitors of the phosphohydrolases. These tools allow, for the first time, delineation of the function of LPA signaling through endogenous receptors. The investigators now intend to use their existing compounds and others in development to learn whether LPA promotes prostate cancer progression. They will assign signaling events in LNCaP and PC-3 cells to specific LPA receptors thus both prioritizing LPA receptors for antagonist development and identifying compounds for testing on prostate cancer cell growth in vivo. Finally they will identify and quantify the species of LPA produced by prostate cancer cells to determine it suitability as a biomarker.
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