TrialLineage Concept
LPA1 receptor
LPA1 (lysophosphatidic acid receptor 1) is a G protein-coupled receptor that mediates many of the profibrotic effects of LPA signaling. It is the molecular target of BMS-986278 and the specific receptor implicated in fibroblast activation in pulmonary fibrosis.
What is LPA1?
LPA1 was the first LPA receptor to be cloned, identified in 1996. It belongs to the endothelial differentiation gene (EDG) family of G protein-coupled receptors and is widely expressed in the body, including in lung fibroblasts, smooth muscle cells, and brain tissue.
When LPA binds LPA1, the receptor activates intracellular signaling pathways (including Rho, MAPK, and PI3K cascades) that promote cell survival, proliferation, migration, and cytoskeletal contraction. In the context of lung fibrosis, LPA1 activation drives fibroblast recruitment to injury sites, resistance to apoptosis, and collagen secretion.
Studies in LPA1 knockout mice showed significantly reduced fibrosis following experimental lung injury, confirming the receptor's role as a profibrotic mediator in the lung.
Connection to the IPF lineage
LPA1 is the direct molecular target of BMS-986278. The entire therapeutic hypothesis depends on the evidence that LPA1 is a key driver of fibroblast activation in IPF lungs. Selective blockade of LPA1 — rather than all LPA receptors — is intended to reduce profibrotic signaling while minimizing off-target effects.