ONO-7300243

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

ONO-7300243 是溶血磷脂酸受体 1 (LPA1；IC50：0.16 μM) 的拮抗剂。

ONO-7300243 is an antagonist of lysophosphatidic acid receptor 1 (LPA1; IC50 : 0.16 μM).

ONO-7300243 shows modest in vitro activity (IC50=0.16 μM). ONO-7300243 exhibits almost identical levels of antagonist activity in vitro.

ONO-7300243 shows good efficacy in vivo. The oral dosing of 17a at 30 mg/kg leads to reduced intraurethral pressure in rats. ONO-7300243 shows stronge effects in vivo (88% inhibition at 10 mg/kg i.d., 62% inhibition at 3 mg/kg i.d.) compared with compound 12g. The results reveal that ONO-7300243 shows good membrane permeability and good metabolic stability against rat liver microsomes (MS). ONO-7300243 exhibits good selectivity towards LPAl over LPA2, most likely because low molecular weight and low lipophilicity lead to reduced compound promiscuity and increased selectivity. ONO-7300243 inhibits the LPA-induced IUP increase in a dose dependent manner (ID50=11.6 mg/kg p.o.) up to 1 h after dosing. Significant effects are observed at 10 and 30 mg/kg (p<0.05 vs.vehicle). ONO-7300243 (30 mg/kg, p.o.) leads to a significant decrease in the IUP in conscious rats without LPA stimulation compared with the vehicle without affecting the mean blood pressure (MBP). The results of a rat pharmacokinetic study of ONO-7300243 show that this material had a rapid clearance (CLtot=15.9 mL/min/kg at 3 mg/kg i.v.) and a short half-life (0.3 h).

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GPCR/G Protein

LPA Receptor

LPA1

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638132-34-0

461.55

C28H31NO5

>98% (HPLC)

DMSO:100 mg/mL (216.66 mM)

COc1cc(cc(OC)c1C)C(=O)N(CCCc1ccccc1)Cc1ccc(CC(O)=O)cc1

2-(4-((35-dimethoxy-4-methyl-N-(3-phenylpropyl)benzamido)methyl)phenyl)acetic acid

(-20℃)

With Ice Pack

≥ 2 years