LPA1 antagonist 1 is a highly selective Lysophosphatidic Acid receptor-1 (LPA1) antagonist (IC50: 25 nM).

LPA1 antagonist 1 is the most selective nonlipid LPA1 antagonist so far reported, to our knowledge. It appears that compounds (e.g., LPA1 antagonist 1) from the N-aryltriazole chemical class are much more selective for LPA1 than compounds from the corresponding pyrazole series. LPA1 antagonist 1 shows very effective and highly selective inhibitory activity toward LPA1, with little inhibition on LPA3 even at very high concentrations. LPA1 antagonist 1 shows the highest LPA1 selectivity and attenuated LPA-induced NHLF proliferation and contraction with high potency. In comparison with Ki16425 and AM095, LPA1 antagonist 1 shows much improved antiproliferative activity .

The LPA-induced histamine level is significantly blocked A clear PK/PD relationship is demonstrated by the correlation between the levels of LPA1 antagonist 1 and LPA-induced histamine concentrations in plasma when mice are orally dosed with LPA1 antagonist 1 (100 mg/kg, aqueous suspension) prior to intravenous LPA injection. Oral dosing of LPA1 antagonist 1 in mice induces a dose-dependent reduction in serum histamine levels induced following intravenous LPA stimulation. The ability of LPA1 antagonist 1 to block histamine release at much lower plasma concentration suggests that further improvement of the pharmacokinetic properties of this chemical class could lower the effective dose. Although AM095 almost fully blocks histamine release (100 mg/kg), the analysis of plasma samples revealed more than 65-fold higher concentrations of AM095 than LPA1 antagonist 1 (100 mg/kg).

1396006-71-5

C28H26N4O4

482.53

LPA1 antagonist 1

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years