Vorapaxar (MK-5348)

製品コードS8067 バッチS806702

化学情報

	Synonyms	SCH 530348	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₉H₃₃FN₂O₄
	分子量	492.58	CAS No.	618385-01-6
Solubility (25°C)*	体外	DMSO	99 mg/mL (200.98 mM)
		Ethanol	99 mg/mL (200.98 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Vorapaxar (SCH 530348, MK-5348) is a potent and orally active thrombin receptor (PAR-1) antagonist with K_i of 8.1 nM.
in vitro	SCH 530348 is a synthetic tricyclic 3-phenylpyridine and an orally active himbacine-based thrombin-receptor antagonist. SCH 530348 shows potent inhibition of thrombin-induced platelet aggregation with an IC50 of 47 nM and haTRAP-induced platelet aggregation with an IC50 of 25 nM, whereas it shows no inhibition of platelet aggregation induced by other agonists such as ADP, collagen and a PAR-4 agonist peptide. SCH 530348 also has no affect on the prothrombin time (PT), partial thromboplastin time (PTT), or activated partial thromboplastin time (aPTT). Moreover, SCH 530348 causes no increase in the bleeding time or in surgical bleeding compared with inactive control. SCH530348 is found to be selective for PAR-1 when tested over a number of ion channels and receptors, including PAR-4 receptor. ^[1]
in vivo	SCH 530348 is well absorbed in rat (68%; 10 mg/kg) and in monkey (82%; 1 mg/kg) models. T_max is observed at about 3 h in rats and 1 h in monkeys. The elimination half-life is 5.1 h in rats and 13 h in monkeys. The oral bioavailability is 33% in rats and 86% in monkeys. In preclinical studies in cynomolgus monkey platelets, oral administration of SCH 530348 at a dose greater than 0.1 mg/kg resulted in 100% inhibition of thrombin-receptor agonist peptide (TRAP)-induced platelet aggregation for 24 h with partial recovery occurring at 48 h. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	In vitro PAR-1 binding assay
キナーゼアッセイ	Human platelet membranes (700 mg) are prepared from 40 units of fresh human platelets. Thrombin receptor antagonists are screened using a modification of the thrombin receptor radioligand binding assay Human platelet membranes (40μg) are incubated with 10nM of [3H]haTRAP (alanine-p-fluorophenylalaninearganine-cyclohexylalanine-homoarganine-[ ³H]phenylalanine amide) in the presence of compounds at concentrations of 1 nM, 3 nM, 30 nM, 100 nM, 300 nM and 1μM (5% DMSO final concentration) in binding buffer (50 mM Tris-HCl, pH 7.5, 10 mM MgCl₂, 1 mM EGTA, 0.1% BSA). The plates are covered and vortex-mixed gently on a plate shaker for 1 h at room temperature. The incubated membranes are harvested using a Packard FilterMate Universal Harvester onto Packard UniFilter GF/C filter plates which are soaked for at least 1 hour in 0.1% polyethyleneimine and then rapidlywashed four times with 300 μL ice cold binding buffer without BSA. MicroScint 20 scintillation cocktail is added to each well, and the plates are counted in a Packard TopCount Microplate Scintillation Counter. The specific binding is defined as the total binding minus the nonspecific binding observed in the presence of excess (50 μM) unlabeled haTRAP.
細胞アッセイ	細胞株	HCASMC cells
	濃度	8.1 nM
	反応時間
	実験の流れ	Cells were treated with different concentrations of SCH 530348.
動物実験	動物モデル	cynomolgus monkeys
	投薬量	0.5, 0.3, 0.1, and 0.05 mg/kg
	投与方法	oral

参考

[1] Chackalamannil S, et al. J Med Chem, 2008, 51(11), 3061-3064.

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長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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