ONO-7300243

Catalog No.S8345 Batch:S834502

Technical Data

Formula	C₂₈H₃₁NO₅
Molecular Weight	461.55	CAS No.	638132-34-0
Solubility (25°C)*	In vitro	DMSO	92 mg/mL (199.32 mM)
		Ethanol	46 mg/mL (99.66 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

ONO-7300243 is a novel, potent LPA1(Lysophosphatidic Acid Receptor) antagonist with an IC50 of 160 nM.

Targets

LPA1 ^[1]
(Cell-free assay)

0.16 μM

In vitro

Although ONO-7300243 showed only modest in vitro activity (IC50 = 0.16 μM), it showed much stronger effects in vivo (88% inhibition at 10 mg/kg i.d., 62% inhibition at 3 mg/kg i.d.). ONO-7300243 showed good membrane permeability and good metabolic stability against rat liver microsomes^[1].

In vivo

ONO-7300243 inhibited the LPA-induced IUP(intraurethral pressure) increase in a dose-dependent manner (ID50 = 11.6 mg/kg p.o.) up to 1 h after dosing. Significant effects were observed at 10 and 30 mg/kg (p<0.05 vs vehicle). ONO-7300243 (30 mg/kg, p.o.) led to a significant decrease in the IUP in conscious rats without LPA stimulation compared with the vehicle without affecting the mean blood pressure (MBP). In a a rat pharmacokinetic study, ONO-7300243 showed a rapid clearance (CLtot = 15.9 mL/min/kg at 3 mg/kg i.v.) and a short half-life (0.3 h)^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines Chinese hamster ovary (CHO) cells Concentrations -- Incubation Time -- Method Chinese hamster ovary (CHO) cells stably expressing human LPA1 were seeded at a density of 2×10⁴ cells per well into 96-well plates and cultured in the culture medium (F-12 Nutrient Mixture (HAM) containing 10% FBS) in a CO2 incubator (37ºC, 5% CO2, 95% air) for 2 days. Load buffer (culture medium containing 5 µM Fura2-AM, 10 mM HEPES (pH 7.55) and 2.5 mM probenecid) was added in each well and incubated in the CO2 incubator for 1 hour. After the load buffer was removed, cells were rinsed with assay buffer at room temperature, and the assay buffer was added to the cells. In the experiment of LPA1 antagonist assay, intracellular Ca2+ concentration was monitored using a fluorescence drug screening system to measure the ratio of fluorescence intensities (f340/f380) at 500 nm. After pretreatment of the antagonists, lysophosphatidic acid (LPA, final 100 nM) was added to the cells. The inhibition rate (%) of the antagonists was calculated from the peak ratio of LPA after treatment of compounds and that of control (DMSO). Furthermore, a non-linear regression analysis was performed using the Sigmoid Emax Model to estimate IC50 values.
Animal Study:^{^[1]}	Animal Models Rats Dosages 3 mg/kg for i.v. or 10 mg/kg for p.o. Administration i.v. or p.o.

Cell Assay:^{^[1]}

Cell lines
Chinese hamster ovary (CHO) cells
Concentrations
--
Incubation Time
--
Method
Chinese hamster ovary (CHO) cells stably expressing human LPA1 were seeded at a density of 2×10⁴ cells per well into 96-well plates and cultured in the culture medium (F-12 Nutrient Mixture (HAM) containing 10% FBS) in a CO2 incubator (37ºC, 5% CO2, 95% air) for 2 days. Load buffer (culture medium containing 5 µM Fura2-AM, 10 mM HEPES (pH 7.55) and 2.5 mM probenecid) was added in each well and incubated in the CO2 incubator for 1 hour. After the load buffer was removed, cells were rinsed with assay buffer at room temperature, and the assay buffer was added to the cells. In the experiment of LPA1 antagonist assay, intracellular Ca2+ concentration was monitored using a fluorescence drug screening system to measure the ratio of fluorescence intensities (f340/f380) at 500 nm. After pretreatment of the antagonists, lysophosphatidic acid (LPA, final 100 nM) was added to the cells. The inhibition rate (%) of the antagonists was calculated from the peak ratio of LPA after treatment of compounds and that of control (DMSO). Furthermore, a non-linear regression analysis was performed using the Sigmoid Emax Model to estimate IC50 values.

Animal Study:^{^[1]}

Animal Models
Rats
Dosages
3 mg/kg for i.v. or 10 mg/kg for p.o.
Administration
i.v. or p.o.

References

[1] Terakado M, et al. ACS Med Chem Lett. 2016, 7(10):913-918.

Selleck's ONO-7300243 has been cited by 1 publication

LPA receptor1 antagonists as anticancer agents suppress human lung tumours. [ Eur J Pharmacol, 2020, 868:172886]	PubMed: 31866407

LPA receptor1 antagonists as anticancer agents suppress human lung tumours. [ Eur J Pharmacol, 2020, 868:172886]

PubMed: 31866407

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SHIPPING AND STORAGE
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