Abstract
Lysophosphatidic acid (LPA) is a bioactive lipid involved in signaling pathways that result in cell survival, proliferation, migration and invasion. These cellular responses are a critical element of both normal development as well as pathophysiology. In particular, dysregulated LPA production and function have been linked with cancer and cardiovascular disease. RxBio, Inc. has generated several series of LPA analogs with varied agonist/antagonist function at the LPA1–3 GPCR targets of LPA signaling. These analogs are simplified relative to LPA through deletion of the glycerol moiety linking the LPA phosphate and fatty acid groups. One of the example compounds was shown to protect intestinal crypt cells from radiation-induced apoptosis in mice when whole body irradiation occurred 2 h after oral dosing.
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