LPAR1 Antagonist

AM095 is a selective LPA₁ receptor antagonist. The IC₅₀ for AM095 antagonism of LPA-induced calcium flux of human or mouse LPA₁-transfected CHO cells is 0.025 and 0.023 μM, respectively.

H2L 5765834 is an antagonist of lysophosphatidic acid receptors LPA₁, LPA₃, and LPA₅, with IC₅₀s of 94, 752, and 463 nM respectively.

ONO-0300302 is an orally active and potent LPA1 (lysophosphatidic acid receptor 1) antagonist, with an IC₅₀ of 0.086 μM. ONO-0300302 is a slow tight binding inhibitor, and its binding affinity increases with time, with K_d of 0.34 nM (37 °C, 2 h). ONO-0300302 can be used for benign prostatic hyperplasia (BPH) research.

PIPE-791 is an orally active, blood-brain barrier-permeable selective antagonist of LPAR1. PIPE-791 inhibits LPA-induced calcium mobilization, collagen expression, histamine release, and the activation of fibroblasts, microglia and macrophages. PIPE-791 induces oligodendrocyte precursor cell differentiation, myelination and remyelination, and increases the number of microglia in the retina of normotensive rats. PIPE-791 protects mature oligodendrocytes from cytokine-induced death, reduces the levels of pulmonary fibrosis markers and alleviates neuroinflammation in preclinical models. PIPE-791 can be used in the research of glaucoma, neuroinflammatory diseases, chronic osteoarthritis pain, idiopathic pulmonary fibrosis and multiple sclerosis.

HL001 is an orally active small molecule inhibitor of Cyclophilin A (CypA) and a receptor antagonist of Lysophosphatidic acid 1 (LPA1). HL001 induces cell cycle arrest and apoptosis of tumor cells by p53. HL001 stabilizes p53 by down-regulating G3BP1, inducing reactive oxygen species and DNA damage. HL001 disrupts the interaction between MDM2 and p53-72R in a CypA dependent manner. HL001 has antitumor activity. HL001 can also be used to study pulmonary fibrosis.

BrP-LPA sodium is a pan-opposite agent for lysophosphatidic acid (LPA). It has antagonistic activity against LPA₁ (IC₅₀ = 4520 nM), LPA₂ (IC₅₀ = 468 nM), LPA₃, and LPA₄. BrP-LPA sodium also has partial agonistic activity for LPA₅, with its EC₅₀ being 1282 nM. BrP-LPA sodium has ATX inhibitory activity. BrP-LPA sodium effectively inhibits the migration and invasion of breast cancer cells. BrP-LPA sodium achieves tumor regression and anti-angiogenesis in mice breast cancer xenograft model. BrP-LPA sodium can be used for the study of breast cancer.

BrP-LPA is a LPA antagonist/ATX inhibitor. BrP-LPA shows pan-antagonist activity towards LPA_1-4 GPCRs. BrP-LPA decreases blood vessel density. BrP-LPA dose-dependently inhibits Lysophosphatidic acid-induced head-dip counts. BrP-LPA exhibits anticancer activity against breast cancer, colon cancer, and lung cancer. BrP-LPA inhibits anxiety-like behavior.