LPA1 receptor antagonist 1

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

LPA1 receptor antagonist 1 是具有高度选择性的，溶血磷脂酸 (LPA1) 受体的一个拮抗剂，其 IC50 值为 25 nM。

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

LPA1 receptor antagonist 1 (compound 2) displays very potent and highly selective inhibitory activity toward LPA1, with little inhibition on LPA3 even at very high concentrations. To our knowledge, LPA1 receptor antagonist 1 is the most selective nonlipid LPA1 antagonist so far reported. It appears that compounds (e.g., LPA1 receptor antagonist 1) from the N-aryltriazole chemical class are much more selective for LPA1 than compounds from the corresponding pyrazole series. In comparison with Ki16425 and AM095, LPA1 receptor antagonist 1 shows much improved antiproliferative activity. LPA1 receptor antagonist 1 demonstrates the highest LPA1 selectivity and attenuated LPA-induced NHLF proliferation and contraction with high potency.

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

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GPCR/G Protein

LPA Receptor

LPA Receptor

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1396006-71-5

482.53

C28H26N4O4

>98% (HPLC)

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C(O)(=O)C1(CC1)C2=CC=C(C=C2)C3=CC=C(C=C3)N4C(NC(O[C@H](C)C5=CC=CC=C5)=O)=C(C)N=N4

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(-20℃)

With Ice Pack

≥ 2 years