Aprepitant

製品コードS1189 バッチS118903

化学情報

	Synonyms	MK-0869, L-754030	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₃H₂₁F₇N₄O₃
	分子量	534.43	CAS No.	170729-80-3
Solubility (25°C)*	体外	DMSO	107 mg/mL (200.21 mM)
		Ethanol	25 mg/mL (46.77 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	Aprepitant is a potent and selective neurokinin-1 receptor antagonist with IC50 of 0.1 nM. Aprepitant reduces levels of pro-inflammatory cytokines including G-CSF, IL-6, IL-8 and TNFα. Aprepitant inhibits HIV infection of human macrophages.
in vitro	Aprepitant antagonizes the effects of substance P by binding to NK-1 receptors primarily in the CNS, but also in the periphery. Aprepitant, at concentrations of 0.1 nM displaces 50% of substance P from hNK1 receptors transfected in CHO or COS cells. In radioligand binding assays, Aprepitant is 3000-fold selective for the human cloned NK1 receptor versus the human cloned NK3 receptor and >50,000-fold selective over the human cloned NK2 receptor. In a range of assays at other human cloned G–protein coupled receptors, Aprepitant retains >50,000-fold selectivity for the human cloned NK1 receptor. Aprepitant is inactive in human monoamine oxidase A and B assays and at human serotonin 5–HT1A, 5–HT2A, 5–HT2c, 5–HT3, 5–HT5, 5–HT6, and 5–HT7 receptors (IC50>3 μM). In the PANLABS panel of radioligand binding screens using native animal tissues, Aprepitant inhibits [³H]substance P binding to native NK1 receptors in rat submaxillary gland; there are no signiﬁcant interactions of Aprepitant with any other native animal G–protein coupled receptors or ion channels examined in the PANLABS screen. Aprepitant is inactive in monoamine uptake site (NE, 5–HT, DA) counterscreens using human and animal tissues (IC50> 3 μM) ^[1]
in vivo	Aprepitant crosses the blood–brain barrier and occupied NK-1 receptors in the brain. Aprepitant has been shown to inhibit both acute and delayed emesis induced by cytotoxic chemotherapeutic such as cisplatin by blocking substance P. Aprepitant (3 mg/kg i.v. or p.o.) inhibits the emetic response to cisplatin (10 mg/kg i.v.). The anti-emetic protection afforded by Aprepitant (0.1 mg/kg i.v.) is enhanced by combined treatment with either dexamethasone (20 mg/kg i.v.) or the 5–HT3 receptor antagonist ondansetron (0.1 mg/kg i.v.). In a model of acute and delayed emesis, ferrets are dosed with cisplatin (5 mg/kg i.p.) and the retching and vomiting response recorded for 72 h. Pretreatment with Aprepitant (4–16 mg/kg p.o.) dose-dependently inhibits the emetic response to cisplatin. Once daily treatment with Aprepitant (2 and 4 mg/kg p.o.) completely prevents retching and vomiting in all ferrets tested. Further when daily dosing began at 24 h after cisplatin injection, when the acute phase of emesis had already become established, Aprepitant (4 mg/kg p.o. at 24 and 48 h after cisplatin) prevents retching and vomiting in three out of four ferrets. ^[1] Aprepitant also plays a key part in transmission of pain impulses from the peripheral receptors to the CNS and is involved in various behavioural, neurochemical and cardiovascular responses to stress. ^[2]

製品説明

Aprepitant is a potent and selective neurokinin-1 receptor antagonist with IC50 of 0.1 nM. Aprepitant reduces levels of pro-inflammatory cytokines including G-CSF, IL-6, IL-8 and TNFα. Aprepitant inhibits HIV infection of human macrophages.

in vitro

Aprepitant antagonizes the effects of substance P by binding to NK-1 receptors primarily in the CNS, but also in the periphery. Aprepitant, at concentrations of 0.1 nM displaces 50% of substance P from hNK1 receptors transfected in CHO or COS cells. In radioligand binding assays, Aprepitant is 3000-fold selective for the human cloned NK1 receptor versus the human cloned NK3 receptor and >50,000-fold selective over the human cloned NK2 receptor. In a range of assays at other human cloned G–protein coupled receptors, Aprepitant retains >50,000-fold selectivity for the human cloned NK1 receptor. Aprepitant is inactive in human monoamine oxidase A and B assays and at human serotonin 5–HT1A, 5–HT2A, 5–HT2c, 5–HT3, 5–HT5, 5–HT6, and 5–HT7 receptors (IC50>3 μM). In the PANLABS panel of radioligand binding screens using native animal tissues, Aprepitant inhibits [³H]substance P binding to native NK1 receptors in rat submaxillary gland; there are no signiﬁcant interactions of Aprepitant with any other native animal G–protein coupled receptors or ion channels examined in the PANLABS screen. Aprepitant is inactive in monoamine uptake site (NE, 5–HT, DA) counterscreens using human and animal tissues (IC50> 3 μM) ^[1]

in vivo

Aprepitant crosses the blood–brain barrier and occupied NK-1 receptors in the brain. Aprepitant has been shown to inhibit both acute and delayed emesis induced by cytotoxic chemotherapeutic such as cisplatin by blocking substance P. Aprepitant (3 mg/kg i.v. or p.o.) inhibits the emetic response to cisplatin (10 mg/kg i.v.). The anti-emetic protection afforded by Aprepitant (0.1 mg/kg i.v.) is enhanced by combined treatment with either dexamethasone (20 mg/kg i.v.) or the 5–HT3 receptor antagonist ondansetron (0.1 mg/kg i.v.). In a model of acute and delayed emesis, ferrets are dosed with cisplatin (5 mg/kg i.p.) and the retching and vomiting response recorded for 72 h. Pretreatment with Aprepitant (4–16 mg/kg p.o.) dose-dependently inhibits the emetic response to cisplatin. Once daily treatment with Aprepitant (2 and 4 mg/kg p.o.) completely prevents retching and vomiting in all ferrets tested. Further when daily dosing began at 24 h after cisplatin injection, when the acute phase of emesis had already become established, Aprepitant (4 mg/kg p.o. at 24 and 48 h after cisplatin) prevents retching and vomiting in three out of four ferrets. ^[1]

Aprepitant also plays a key part in transmission of pain impulses from the peripheral receptors to the CNS and is involved in various behavioural, neurochemical and cardiovascular responses to stress. ^[2]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	Cell-free assays
	濃度	0.1 nM
	反応時間
	実験の流れ
動物実験	動物モデル	Male ferrets
	投薬量	4, 8 or 16 mg/kg
	投与方法	p.o.

参考

カスタマーフィードバック

: , , J Hepatol, 2014, 60(5):985-94.

: Data from [Data independently produced by , , Cell Death Differ, 2016, 23(4):608-15]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Tumor Treating Fields (TTFields) combined with the drug repurposing approach CUSP9v3 induce metabolic reprogramming and synergistic anti-glioblastoma activity in vitro [ Br J Cancer, 2024, 10.1038/s41416-024-02608-8]	PubMed: 38396172
Substance P Exacerbates the Inflammatory and Pro-osteoclastogenic Responses of Murine Osteoclasts and Osteoblasts to Staphylococcus aureus [ Inflammation, 2023, 46(1):256-269]	PubMed: 36040535
CK2-induced cooperation of HHEX with the YAP-TEAD4 complex promotes colorectal tumorigenesis [ Nat Commun, 2022, 13(1):4995]	PubMed: 36008411
HPV-CCDC106 integration promotes cervical cancer progression by facilitating the high expression of CCDC106 after HPV E6 splicing [ J Med Virol, 2022, 10.1002/jmv.28009]	PubMed: 35854676
Asialoglycoprotein receptor 1 functions as a tumor suppressor in liver cancer via inhibition of STAT3 [ Cancer Res, 2022, CAN-21-4337]	PubMed: 36043912
Copper enhances genotoxic drug resistance via ATOX1 activated DNA damage repair [ Cancer Lett, 2022, 536:215651]	PubMed: 35315340
LGL1 binds to Integrin β1 and inhibits downstream signaling to promote epithelial branching in the mammary gland [ Cell Rep, 2022, 38(7):110375]	PubMed: 35172155
TMEM43 promotes pancreatic cancer progression by stabilizing PRPF3 and regulating RAP2B/ERK axis [ Cell Mol Biol Lett, 2022, 27(1):24]	PubMed: 35260078
Cathepsin B/HSP70 complex induced by Ilexsaponin I suppresses NLRP3 inflammasome activation in myocardial ischemia/reperfusion injury [ Phytomedicine, 2022, 105:154358]	PubMed: 35952578
PACS-2 Ameliorates Tubular Injury by Facilitating Endoplasmic Reticulum-Mitochondria Contact and Mitophagy in Diabetic Nephropathy [ Diabetes, 2022, 71(5):1034-1050]	PubMed: 35133431

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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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