| Bioactivity | ONO-7300243 is a novel, potent lysophosphatidic acid receptor 1 (LPA1) antagonist with IC50 of 0.16 μM. | ||||||||||||
| Target | IC50: 0.19-0.13 μM (LPA1) | ||||||||||||
| Invitro | ONO-7300243 shows modest in vitro activity (IC50=0.16 μM). ONO-7300243 exhibits almost identical levels of antagonist activity in vitro[1]. | ||||||||||||
| In Vivo | 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)[1]. | ||||||||||||
| Name | ONO-7300243 | ||||||||||||
| CAS | 638132-34-0 | ||||||||||||
| Formula | C28H31NO5 | ||||||||||||
| Molar Mass | 461.55 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
|
||||||||||||
| Reference | [1]. Terakado M, et al. Discovery of ONO-7300243 from a Novel Class of Lysophosphatidic Acid Receptor 1 Antagonists: From Hit to Lead. ACS Med Chem Lett. 2016 Aug 19;7(10):913-918. |