Simvastatin

製品コードS1792 バッチS179206

化学情報

	Synonyms	MK 733	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₅H₃₈O₅
	分子量	418.57	CAS No.	79902-63-9
Solubility (25°C)*	体外	DMSO	83 mg/mL (198.29 mM)
		Ethanol	83 mg/mL (198.29 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	Simvastatin is a competitive inhibitor of HMG-CoA reductase with K_i of 0.1-0.2 nM in cell-free assays. Simvastatin induces ferroptosis, mitophagy, autophagy and apoptosis.
in vitro	Prior to use in cell assays, Simvastatin needs to be activated by NaOH in EtOH treatment. Simvastatin inhibits cholesterol synthesis in mouse L-M cell (fibroblast), rat H4II E cell (liver), and human Hep G2 cell (liver) with IC50 of 19.3 nM, 13.3 nM and 15.6 nM, respectively. ^[1] Simvastatin treatment leads to a dose-dependent increase in serine 473 phosphorylation of Akt within 30 minutes, with maximal phosphorylation occurring at 1.0 µM. Simvastatin (1.0 μM) enhances phosphorylation of the endogenous Akt substrate endothelial nitric oxide synthase (eNOS), inhibits serum-free media undergo apoptosis and accelerates vascular structure formation. ^[2] Simvastatin displays anti-inﬂammatory effects in vitro. Simvastatin (10 μM) reduces anti-CD3/anti-CD28 antibody-stimulated proliferation of PB-derived mononuclear cells and synovial ﬂuid cells from rheumatoid arthritis blood, as well as IFN-γ release. Simvastatin (10 μM) suppresses cell-mediated macrophage TNF-γ release induced via cognate interactions by ~30%. ^[3]
in vivo	Simvastatin orally administration inhibits the conversion of radiolabeled acetate to cholesterol with IC50 of 0.2 mg/kg. ^[1] Simvastatin (4 mg/day) orally administration for 13 weeks to rabbits fed an atherogenci cholesterol-rich diet, returns the cholesterol-induced increases in total cholesterol, LDL-cholesterol and HDL-cholesterol to normal level. ^[4] Simvastatin (6 mg/kg) produces an increase in LDL receptor-dependent binding and increases the number of hepatic LDL receptors in rabbits fed a diet containing 0.25% cholesterol. ^[5] Simvastatin influences inflammation independent of its effect on plasma cholesterol level. In cynomolgus monkeys consumed an atherogenic diet, Simvastatin (20 mg/kg/day) induces a 1.3-fold less macrophage content in lesions, and 2-fold less vascular cell adhesion molecule-1, interleukin-1beta, and tissue factor expression, companied by a 2.1-fold increases in lesional smooth muscle cell and collagen content. ^[6]

製品説明

Simvastatin is a competitive inhibitor of HMG-CoA reductase with K_i of 0.1-0.2 nM in cell-free assays. Simvastatin induces ferroptosis, mitophagy, autophagy and apoptosis.

in vitro

Prior to use in cell assays, Simvastatin needs to be activated by NaOH in EtOH treatment. Simvastatin inhibits cholesterol synthesis in mouse L-M cell (fibroblast), rat H4II E cell (liver), and human Hep G2 cell (liver) with IC50 of 19.3 nM, 13.3 nM and 15.6 nM, respectively. ^[1]

Simvastatin treatment leads to a dose-dependent increase in serine 473 phosphorylation of Akt within 30 minutes, with maximal phosphorylation occurring at 1.0 µM. Simvastatin (1.0 μM) enhances phosphorylation of the endogenous Akt substrate endothelial nitric oxide synthase (eNOS), inhibits serum-free media undergo apoptosis and accelerates vascular structure formation. ^[2]

Simvastatin displays anti-inﬂammatory effects in vitro. Simvastatin (10 μM) reduces anti-CD3/anti-CD28 antibody-stimulated proliferation of PB-derived mononuclear cells and synovial ﬂuid cells from rheumatoid arthritis blood, as well as IFN-γ release. Simvastatin (10 μM) suppresses cell-mediated macrophage TNF-γ release induced via cognate interactions by ~30%. ^[3]

in vivo

Simvastatin orally administration inhibits the conversion of radiolabeled acetate to cholesterol with IC50 of 0.2 mg/kg. ^[1]

Simvastatin (4 mg/day) orally administration for 13 weeks to rabbits fed an atherogenci cholesterol-rich diet, returns the cholesterol-induced increases in total cholesterol, LDL-cholesterol and HDL-cholesterol to normal level. ^[4]

Simvastatin (6 mg/kg) produces an increase in LDL receptor-dependent binding and increases the number of hepatic LDL receptors in rabbits fed a diet containing 0.25% cholesterol. ^[5]

Simvastatin influences inflammation independent of its effect on plasma cholesterol level. In cynomolgus monkeys consumed an atherogenic diet, Simvastatin (20 mg/kg/day) induces a 1.3-fold less macrophage content in lesions, and 2-fold less vascular cell adhesion molecule-1, interleukin-1beta, and tissue factor expression, companied by a 2.1-fold increases in lesional smooth muscle cell and collagen content. ^[6]

プロトコル(参考用のみ)

キナーゼアッセイ	HMG-CoA reductase activity assay
キナーゼアッセイ	The total volume of each assay is 95 μL and the reaction mixture contained 10 μL of the inhibiting compound to be tested and 85 μL of the incubating buffer containing 2 mg/mL liver microsomes, 0.1 M KH₂PO₄, pH 7.2, 5.7 mM dithiothreitol, 10 mM glucose-6-phosphate, 2 U/mL glucose-6-phosphate dehydrogenase, 1 mM NADP, 10 μM miconazole. Control experiments are done without NADPH generating system. All samples are incubated 10 min at 37 ℃ before addition of 5μL of substrate (unlabelled and 14C-HMG-3-hydroxy-3-methyl glutaryl CoA, final concentration 50 μM, 2.5 nCi/nmole). After 30 min at 37 ℃, the reaction is stopped by adding 27 μL 1N HCl and 20 μL of unlabelled mevalonolactone (200 μg/assay). The conversion of mevalonic acid to lactone is performed at room temperature for 60 min.
細胞アッセイ	細胞株	HUVECs
	濃度	1 μM
	反応時間	30 minutes
	実験の流れ	HUVECs were treated with simvastatin for 30 minutes.
動物実験	動物モデル	Male Japanese white rabbits
	投薬量	2.5, 5, & 10 mg/kg
	投与方法	Oral

参考

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カスタマーフィードバック

: , , JAMA Oncol, 2015, 1(4):495-504.

: Data from [Data independently produced by , , Haematologica, 2018, doi: 10.3324/haematol.2018.204701]

: Data from [Data independently produced by , , Cell Physiol Biochem, 2018, 46(2):618-632]

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：

Neuronal γ-secretase regulates lipid metabolism, linking cholesterol to synaptic dysfunction in Alzheimer's disease [ Neuron, 2023, S0896-6273(23)00513-5]	PubMed: 37543038
Caffeine Supplementation and FOXM1 Inhibition Enhance the Antitumor Effect of Statins in Neuroblastoma [ Cancer Res, 2023, 83(13):2248-2261]	PubMed: 37057874
MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer [ Cell Death Dis, 2023, 14(4):234]	PubMed: 37005437
NFYC-37 promotes tumor growth by activating the mevalonate pathway in bladder cancer [ Cell Rep, 2023, 42(8):112963]	PubMed: 37561631
Mitotic perturbation is a key mechanism of action of decitabine in myeloid tumor treatment [ Cell Rep, 2023, 42(9):113098]	PubMed: 37714156
Hypoxia-altered cholesterol homeostasis enhances the expression of interferon-stimulated genes upon SARS-CoV-2 infections in monocytes [ Front Immunol, 2023, 14:1121864]	PubMed: 37377965
Inference of glioblastoma migration and proliferation rates using single time-point images [ Commun Biol, 2023, 6(1):402]	PubMed: 37055469
Metformin and simvastatin synergistically suppress endothelin 1-induced hypoxia and angiogenesis in multiple cancer types [ Cancer Sci, 2023, 114(2):640-653]	PubMed: 36156330
Activation of the mevalonate pathway in response to anti-cancer treatments drives glioblastoma recurrences through activation of Rac-1 [ bioRxiv, 2023, 2023.07.23.550205]	PubMed: 37546917
SREBP activation contributes to fatty acid accumulations in necroptosis [ RSC Chem Biol, 2023, 4(4):310-322]	PubMed: 37034406

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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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