AM095 free acid

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

AM095（游离酸）是一种有效的 LPA1 受体拮抗剂（重组人或小鼠 LPA1 的 IC50 值：0.98 和 0.73 μM）。在体外，AM095 是一种有效的 LPA 受体拮抗剂，因为它抑制 GTPγS 与中国仓鼠卵巢 (CHO) 细胞膜的结合过表达重组人或小鼠 LPA，IC 值分别为 0.98 和 0.73 μM，并且不表现出 LPA 激动作用。

AM095 (free acid) is a potent LPA1 receptor antagonist (IC50s: 0.98 and 0.73 μM for recombinant human or mouse LPA1).In vitro, AM095 was a potent LPA receptor antagonist because it inhibited GTPγS binding to Chinese hamster ovary (CHO) cell membranes overexpressing recombinant human or mouse LPA with IC values of 0.98 and 0.73 μM, respectively, and exhibited no LPA agonism.?In functional assays, AM095 inhibited LPA-driven chemotaxis of CHO cells overexpressing mouse LPA (IC = 778 nM) and human A2058 melanoma cells (IC = 233 nM).In vivo, AM095: 1) had high oral bioavailability and a moderate half-life and was well tolerated at the doses tested in rats and dogs after oral and intravenous dosing, 2) dose-dependently reduced LPA-stimulated histamine release, 3) attenuated bleomycin-induced increases in collagen, protein, and inflammatory cell infiltration in bronchalveolar lavage fluid, and 4) decreased kidney fibrosis in a mouse unilateral ureteral obstruction model.

AM095 inhibits the LPA-induced calcium flux of CHO cells stably transfected with human or mouse LPA1. 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. AM095 reduces LPA-induced vasorelaxation by appr 90% at 10 μM as compared to vehicle control. AM095 inhibits LPA-driven chemotaxis of CHO cells overexpressing mouse LPA1 (IC50=778 nM) and human A2058 melanoma cells (IC50=233 nM).

Pharmacological antagonism of LPA1 with AM095 significantly attenuates bleomycin-induced dermal fibrosis. AM095 has high oral bioavailability and a moderate half-life and is well tolerated at the doses tested in rats and dogs after oral and intravenous dosing. AM095 dose-dependently reduces LPA-stimulated histamine release. AM095 attenuates bleomycin-induced increases in collagen, protein, and inflammatory cell infiltration in bronchalveolar lavage fluid. AM095 decreases kidney fibrosis in a mouse unilateral ureteral obstruction model.

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GPCR/G Protein

LPA Receptor

LPA1

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1228690-36-5

456.49

C27H24N2O5

>98% (HPLC)

DMSO:67.3 mg/mL (147.43 mM; Need ultrasonic and warming)

O=C(CC1=CC=C(C=C1)C2=CC=C(C=C2)C3=C(C(C)=NO3)NC(O[C@H](C)C4=CC=CC=C4)=O)O

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(-20℃)

With Ice Pack

≥ 2 years