title: Lysophosphatidic acid receptor (LPAR) modulators: The current pharmacological toolbox.
abstract: Lysophosphatidic acids (LPA) are key lipid-signalling molecules that regulate a remarkably diverse set of cellular events, such as motility, chemotaxis, cell cycle progression, viability, and wound healing. The physiological and pathophysiological consequences of LPA signalling are evident and misregulation of LPA signalling can lead to pathologies like cancer, atherosclerosis, ischaemia, and fibrosis. LPA exerts its biological actions mainly through several types of G protein-coupled receptors, some of which display opposing or redundant effects. For this reason, selective LPA receptor small-molecule ligands can shine light on LPA biology and present an exciting opportunity for drug discovery endeavours. This review provides insights into the detailed chemical nature and pharmacological profile of the small-molecules thus far developed as LPA receptor modulators, as well as information on the preparation of key pharmaceuticals. This summary will facilitate future research efforts and nurture collaboration between chemists and biologists working in this emerging field.
authors.affiliation: Science for Life Laboratory, Division of Translational Medicine & Chemical Biology, Department of Medical Biochemistry & Biophysics, Karolinska Institutet, Stockholm S-171 21, Sweden. Electronic address: sabin.llona.minguez@scilifelab.se.
authors.forename: Sabin
authors.initials: S
authors.lastname: Llona-Minguez
authors.affiliation: Faculty of Medicine, McGill University, Montreal, QC H3G 1Y6, Canada.
authors.forename: Artin
authors.initials: A
authors.lastname: Ghassemian
authors.affiliation: Science for Life Laboratory, Division of Translational Medicine & Chemical Biology, Department of Medical Biochemistry & Biophysics, Karolinska Institutet, Stockholm S-171 21, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Helleday
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D008246:Lysophospholipids / Q000378:metabolism; D000069437:Pharmacological Phenomena; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008024:Ligands; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid
keywords: Agonist; Antagonist; Cancer; GPCR; Idiopathic pulmonary fibrosis; Lysophosphatidic acid; Small molecule; Systemic sclerosis