Simvastatin

別名：MK 733

製品コード：S1792 純度：99.92%

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.

CAS No. 79902-63-9

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
25mg	JPY 22000	国内在庫あり
100mg	JPY 44500	国内在庫あり
1g	JPY 145500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（64）

製品安全説明書

現在のバッチを見る：純度： 99.92%

99.92

Simvastatin関連製品

関連化合物ライブラリー	Metabolism Compound Library Anti-cancer Metabolism Compound Library Glutamine Metabolism Compound Library Carbohydrate Metabolism Compound Library Lipid Metabolism Compound Library	もっと見る

シグナル伝達経路

HMG-CoA Reductaseシグナル伝達経路

HMG-CoA Reductase阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
RASMC cells	Function assay	2 μM	72 h	Inhibition of rat Ftase in RASMC cells assessed as reduction in Ras prenylation at 2 uM after 72 hrs by Western blot analysis	21802946
human A549 cells	Cytotoxic assay		72 h	Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50=16.3 μM	23570542
rat liver hepatocytes	Function assay		4 h	Inhibition of cholesterol synthesis in rat liver hepatocytes after 4 hrs, IC50=1.3 nM	17560788
mouse MEF cells	Cytotoxic assay			Cytotoxicity against mouse MEF cells after 72 hrs by MTT assay, IC50=36.7 μM	23570542
human HS68 cells	Cytotoxic assay			Cytotoxicity against human HS68 cells after 72 hrs by MTT assay, IC50=26.4 μM	23570542
HEK293 cells	Function assay			Inhibition of OATP1B1 (unknown origin) expressed in HEK293 cells using estradiol-17beta-glucuronide substrate, IC50=4.4 μM	22587986
HepG2 cells	Function assay			In vitro inhibitory activity was evaluated on cholesterol biosynthesis in HepG2 cells, IC50=0.04 μM	14741258
rat L6 cells	Function assay			Inhibition of cholesterol synthesis in rat L6 cells assessed as incorporation of [14C]acetate into cholesterol, IC50=0.027 μM	18412317
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

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.

Targets

HMG-CoA reductase ^[1]
(Cell-free assay)

0.1-0.2 nM(Ki)

In Vitro
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]
Kinase Assay	HMG-CoA reductase activity assay
Kinase Assay	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.
細胞実験	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.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	Nrf2 p-RB / Cyclin D1 / p21 / p27 / PCNA / CDC45 AMPK / p-AMPK / P70S6 / p-P70S6 / LC3 / Atg7 Bcl-2 / PARP / Caspase-3 / Cleaved Caspase-3 HMGCR		27323826
	Immunofluorescence	Nrf2 LC3A/B		27323826
	Growth inhibition assay	Cell viability		26503475

In Vivo
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]
動物実験	動物モデル	Male Japanese white rabbits
	投与量	2.5, 5, & 10 mg/kg
	投与経路	Oral

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT05771675	Not yet recruiting	Recurrent Acute Pancreatitis\|Chronic Pancreatitis	Cedars-Sinai Medical Center\|United States Department of Defense	January 2024	Early Phase 1
NCT05542095	Withdrawn	Olfactory Disorder\|COVID-19	Washington University School of Medicine\|Duke University	May 1 2023	Phase 1
NCT05613400	Enrolling by invitation	Diabetes Mellitus Type 2	The University of Hong Kong	April 13 2022	Phase 4

参考
[1] Slater EE, et al. Drugs. 1988, 36 Suppl 3, 72-82. [2] Kureishi Y, et al. Nat Med, 2000, 6(9), 1004-1010. [3] Leung BP, et al. J Immunol, 2003, 170(3), 1524-1530. [4] Kobayashi M, et al. Jpn J Pharmacol, 1989, 49(1), 125-133. [5] Ishida F, et al. Biochim Biophys Acta, 1990, 1042(3), 365-373. [6] Sukhova GK, et al. Arterioscler Thromb Vasc Biol, 2002, 22(9), 1452-1458. [7] Dansette PM, et al. Exp Toxicol Pathol, 2000, 52(2), 145-148. + 展開

参考

+ 展開

化学情報

分子量	418.57	化学式	C₂₅H₃₈O₅
CAS No.	79902-63-9	SDF	Download Simvastatin SDFをダウンロードする
Smiles	CCC(C)(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC3CC(CC(=O)O3)O)C
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 83 mg/mL ( (198.29 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 83 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

よくある質問（FAQ）

質問1:
Can you please advise if Simvastatin has been tested effectively for in vivo use in mice? What solvent can be used to deliver Simvastatin in vivo?

回答
This compound is an oral drug and a lot of studies report its use in mice. According to this paper (http://atvb.ahajournals.org/content/21/1/115.full), 0.5% Methyl-cellulose can be used as the vehicle.

質問2:
If any specific protocols exist for in vitro use, specifically any steps required to activate the compound?

回答
This product is supplied in an inactive form and requires treatment with NaOH in EtOH followed by neutralization to pH 7.2 for activation. Please find the details from the following reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739764/.

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