Home Metabolism HMG-CoA Reductase inhibitor Simvastatin (MK-733)

연구용

Simvastatin (MK-733) HMG-CoA Reductase inhibitor

제품 번호: S1792

Simvastatin is a competitive inhibitor of HMG-CoA reductase with Ki of 0.1-0.2 nM in cell-free assays. Simvastatin induces ferroptosis, mitophagy, autophagy and apoptosis.
Simvastatin (MK-733) HMG-CoA Reductase inhibitor Chemical Structure

화학 구조

분자량: 418.57

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품질 관리 (Quality Control)

배치: 순도: 99.92%
99.92

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
rat liver hepatocytes Function assay 4 h Inhibition of cholesterol synthesis in rat liver hepatocytes after 4 hrs, IC50=1.3 nM
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
HepG2 cells Function assay In vitro inhibitory activity was evaluated on cholesterol biosynthesis in HepG2 cells, IC50=0.04 μM
HEK293 cells Function assay Inhibition of OATP1B1 (unknown origin) expressed in HEK293 cells using estradiol-17beta-glucuronide substrate, IC50=4.4 μM
human A549 cells Cytotoxic assay 72 h Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50=16.3 μM
human HS68 cells Cytotoxic assay Cytotoxicity against human HS68 cells after 72 hrs by MTT assay, IC50=26.4 μM
mouse MEF cells Cytotoxic assay Cytotoxicity against mouse MEF cells after 72 hrs by MTT assay, IC50=36.7 μM
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
클릭하여 더 많은 세포주 실험 데이터 보기

화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 418.57 화학식

C25H38O5

 보관 (수령일로부터)
CAS 번호 79902-63-9 SDF 다운로드 원액 보관

동의어 MK 733 Smiles CCC(C)(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC3CC(CC(=O)O3)O)C

용해도 (Solubility)

In vitro
배치:

DMSO : 83 mg/mL (198.29 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 83 mg/mL

Water : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

Targets/IC50/Ki
HMG-CoA reductase
(Cell-free assay)
0.1-0.2 nM(Ki)
시험관 내(In vitro)

Prior to use in cell assays, Simvastatin needs to be activated by NaOH in EtOH treatment. This compound 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.

This compound treatment leads to a dose-dependent increase in serine 473 phosphorylation of Akt within 30 minutes, with maximal phosphorylation occurring at 1.0 µM. It (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.

This chemical displays anti-inflammatory effects in vitro. It (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. This compound (10 μM) suppresses cell-mediated macrophage TNF-γ release induced via cognate interactions by ~30%.

키나아제 분석
HMG-CoA reductase activity 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.
생체 내(In vivo)

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

This compound (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.

This compound (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.

This compound influences inflammation independent of its effect on plasma cholesterol level. In cynomolgus monkeys consumed an atherogenic diet, this compound (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.

참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/2724674/
  • [5] https://pubmed.ncbi.nlm.nih.gov/2106347/
  • [6] https://pubmed.ncbi.nlm.nih.gov/12231565/
  • [7] https://pubmed.ncbi.nlm.nih.gov/10965989/

적용 분야 (Applications)

방법 바이오마커 이미지 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
S1792-WB1
27323826
Immunofluorescence Nrf2 LC3A/B
S1792-IF1
27323826
Growth inhibition assay Cell viability
S1792-viability1
26503475

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
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
NCT06207682 Completed
Healthy Volunteers
Amgen
 June 28 2022 Phase 1

자주 묻는 질문 (Frequently Asked Questions)

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

답변:
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.

질문 2:
If any specific protocols exist for in vitro use, specifically any steps required to activate it?

답변:
This compound 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/.