A patent review of LPAR1 antagonists (2010 – present)

INTRODUCTION: Lysophosphatidic acid receptor 1 (LPAR1), a G protein-coupled receptor, mediates diverse biological effect. Substantial evidence from human patients and experimental models demonstrates that pathological hyperactivation of LPAR1 in fibroblasts and myofibroblasts contributes to disease progression, establishing it as a key pathological driver in idiopathic pulmonary fibrosis (IPF). AREAS COVERED: This review systematically analyzes peer-reviewed literature retrieved from Web of Science and PubMed, alongside publicly disclosed patents obtained via the IncoPat Patent Search and Analysis platform, covering the period from 2010 to the present. Clinical data were sourced from the Cortellis Drug Discovery Intelligence database. EXPERT OPINION: Small-molecule LPAR1 antagonists show promise as novel therapeutics for IPF, as evidenced by their attenuation of disease progression in two phase II clinical trials. Despite these advancements, LPAR1 antagonist development faces several medicinal chemistry challenges, including the absence of rational structure-based drug design and difficulties in optimizing ADMET properties. Future development avenues include exploring combination therapies, expanding indications, developing long-acting formulations, and investigating novel modalities such as LPAR1-targeting proteolysis-targeting chimeras (PROTACs) and small-interfering RNA (siRNA) therapeutics directed against LPAR1.