Rimonabant (SR141716)

製品コードS3021 バッチS302101

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₂H₂₁Cl₃N₄O
	分子量	463.79	CAS No.	168273-06-1
Solubility (25°C)*	体外	DMSO	25 mg/mL (53.9 mM)
		Ethanol	2 mg/mL (4.31 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	Rimonabant (SR141716) is a selective antagonist of CB1 with IC50 of 13.6 nM and EC50 of 17.3 nM in hCB1 transfected HEK 293 membrane. Rimonabant is also a dual inhibitor of acyl CoA:cholesterol acyltransferases(ACAT) 1 and 2 and inhibits mycobacterial MmpL3.
in vitro	Rimonabant dose-dependently reduces ACAT activity in Raw264.7macrophages with IC50 of 2.9 μM and isolated peritoneal macrophages. Rimonabant inhibits ACATactivity in intact CHO-ACAT1 and CHO-ACAT2 cells and in cell-free assays with approximately equal efficiency with IC50 of 1.5 μM and 2.2 μM for CHO-ACAT1 and CHO-ACAT2, respectively. Consistent with ACAT inhibition, Rimonabant treatment blocks ACAT dependent processes in macrophages, oxysterol-induced apoptosis and acetylated-LDL induced foam cell formation. ^[2] Rimonabant antagonizes the inhibitory effects of cannabinoid receptor agonists on both mouse vas deferens contractions and adenylyl cyclase activity in rat brain membranes in a concentration-dependent manner. ^[3] Rimonabant significantly reduces cell growth and induces cell death of human colorectal cancer cells (DLD-1, CaCo-2 and SW620). Rimonabant is able to alter cell cycle distribution in all the cell lines tested. Particularly, Rimonabant produces a G2/M cell cycle arrest in DLD-1 cells without inducing apoptosis or necrosis. ^[4]
in vivo	Rimonabant is administered intraperitoneally or orally potently and dose-dependently antagonize classical pharmacological and behavioural effectos of cannabinoid receptor agonists. ^[3] In the mouse model of azoxymethane-induced colon carcinogenesis, Rimonabant significantly decreased aberrant crypt foci (ACF) formation, which precedes colorectal cancer. ^[4] Rimonabant (10 mg/kg by gavage) is fed for 2 weeks to 3-month-old male obese Zucker rats as an impaired glucose tolerance model and for 10 weeks to 6-month-old male obese Zucker rats as a model of the metabolic syndrome. RANTES (Regulated upon Activation, Normal T cell Expressed, and Secreted) and MCP-1 (monocyte chemotactic protein-1) serum levels are increased in obese vs lean Zucker rats and significantly reduced by long-term treatment with Rimonabant, which slowes weight gain in rats with the metabolic syndrome. Neutrophils and monocytes are significantly increased in young and old obese vs lean Zucker rats and lowered by Rimonabant. Platelet-bound fibrinogen is significantly enhanced in obese vs lean Zucker rats of both age, and is reduced by Rimonabant. Platelets from obese rats are more sensitive to thrombin-induced aggregation and adhesion to fibrinogen, which are both attenuated by Rimonabant therapy. ^[5]
特徴	Efficacious to induce weight reduction and improvements in cardiometabolic risk factors, however was withdrawn in 2009 due to severe depressive disorder and anxiety.

プロトコル(参考用のみ)

キナーゼアッセイ	Radioligand Binding Assay
キナーゼアッセイ	Human CB1 and CB2 stably transfect HEK 293 cells and cell membrane is purified. 0.2-8 μg of the purified membrane is incubated with 0.75 nM [³H] CP55,940 and Rimonabant in the incubation buffer (50 mM Tris-HCl, 5 mM MgCl₂, 1 mM EDTA, 0.3%BSA, pH 7.4). The non-specific binding is defined in the presence of 1 μM of CP55,940. The reactions are incubated for one and a half hours at 30 °C in Multiscreen. The reactions are terminated by manifold filtration and washed four times with ice-cold wash buffer (50mM Tris, pH 7.4, 0.25% BSA).The radioactivity bound to the filters is measured by Topcount. The IC50 is determined as the concentration of Rimonabant required to inhibit 50% of the binding of [³H] CP55,940 and calculated by non-linear regression.
細胞アッセイ	細胞株	Raw 264.7 cells
	濃度	0,1,4 μM
	反応時間	17 hours
	実験の流れ	Raw 264.7 cells (2 × 10⁶ /well) in 12-well plates are rinsed with PBS and refed culture media supplemented with varying amounts of Rimonabant 1 hour prior to supplementation with 7-ketocholesterol (7KC). All wells are adjusted to receive equal amounts of vehicle. Following 16-hour incubation, caspase-3 and caspase 3-like activity are determined using a fluorogenic substrate (Ac-DEVD-AFC) and a spectrofluorometer equipped with a microplate reader.
動物実験	動物モデル	Male mice and male rats
	投薬量	20 ml/kg (mice) and 5 ml/kg (rats)
	投与方法	Rimonabant is administered i.p. (30 minutes) or p.o. (1hour) before the i.v. injection of WIN55212-2.

参考

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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：

Effects of prenatal exposure to THC on hippocampal neural development in offspring [ Toxicol Lett, 2023, 374:48-56]	PubMed: 36529297
OTUD1 stabilizes PTEN to inhibit the PI3K/AKT and TNF-alpha/NF-kappaB signaling pathways and sensitize ccRCC to TKIs [ Int J Biol Sci, 2022, 18(4):1401-1414]	PubMed: 35280681
Endocannabinoids regulate cocaine-associated memory through brain AEA-CB1R signalling activation [ Mol Metab, 2022, 65:101597]	PubMed: 36096452
Endocannabinoid signaling regulates the reinforcing and psychostimulant effects of ketamine in mice [ Nat Commun, 2020, 11(1):5962]	PubMed: 33235205
The fatty-acid amide hydrolase inhibitor URB597 inhibits MICA/B shedding [ Sci Rep, 2020, 10(1):15556]	PubMed: 32968163
Rimonabant suppresses RNA transcription of hepatitis B virus by inhibiting hepatocyte nuclear factor 4α. [ Microbiol Immunol, 2020, 10.1111/1348-0421.12777]	PubMed: 31981244
Effects of Δ(9)-tetrahydrocannabinol (THC) on human amniotic epithelial cell proliferation and migration [ Toxicology, 2018, 394:19-26]	PubMed: 29191629

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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