Lysophosphatidic acid (LPA) receptor modulators: Structural features and recent development

Lysophosphatidic acid (LPA) activates six LPA receptors (LPAR1-6) and regulates various cellular activities such as cell proliferation, cytoprotection, and wound healing. Many studies elucidated the pathological outcomes of LPA are due to the alteration in signaling pathways, which include migration and invasion of cancer cells, fibrosis, atherosclerosis, and inflammation. Current pathophysiological research on LPA and its receptors provides a means that LPA receptors are new therapeutic targets for disorders associated with LPA. Various chemical modulators are developed and are under investigation to treat a wide range of pathological complications. This review summarizes the physiological and pathological roles of LPA signaling, development of various LPA modulators, their structural features, patents, and their clinical outcomes. [Display omitted] •Many studies illustrated the pathological outcomes of LPA are due to the alteration in signaling pathways.•LPARs are unique therapeutic targets to explore new chemical modulators in treating present and future health challenges.•The structural requirements of the chemical scaffold plays a vital role in eliciting agonism/antagonism at the LPARs.•Emphasized the structure relationships of LPA agonists/antagonists of lipid and non-lipid analogs.•The LPA receptor modulators under clinical trials and patent are summarized.