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Lovastatin (Mevinolin, MK-803) HMG-CoA Reductase remmer

Name: Lovastatin (Mevinolin, MK-803)
Brand: Selleck Chemicals
SKU: S2061
Rating: 5 (69 reviews)

Cat.nr.S2061

Lovastatin is een remmer van HMG-CoA reductase met een IC50 van 3,4 nM in een celvrije test, gebruikt voor het verlagen van cholesterol (hypolipidemisch middel). Lovastatin activeert autophagy.

Lovastatin (Mevinolin, MK-803) HMG-CoA Reductase remmer Chemical Structure

Chemische structuur

Molecuulgewicht: 404.54

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Kwaliteitscontrole

Batch: Zuiverheid: 99.99%

99.99

Gerelateerde doelwitten	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism
Overig HMG-CoA Reductase Inhibitoren	Mevastatin SR-12813 Clinofibrate Dihydrolanosterol 7-ketocholesterol Cerivastatin sodium

Celkweek, behandeling & werkzame concentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	PMID
HES 9 cell line	Function assay			Concentration required to inhibit HMG-CoA reductase by 50% was determined in HES 9 cell line, IC50=0.013 μM	1527791
HEP G2	Function assay			Inhibition of the incorporation of sodium [14C]acetate into cholesterol in HEP G2 cells., IC50=0.05μM.	1656041
HEP G2	Function assay			Inhibition of cellular HMG-CoA reductase in cultures of hepatic cells (HEP G2, a human hepatoma cell line), IC50=0.00005μM.	2153213
HEP G2	Function assay			Inhibition of cellular HMG-CoA reductase in cultures of human HEP G2 cells, determined by decreased incorporation of sodium [14C]acetate into cholesterol., IC50=0.05μM.	2296036
HEP G2	Function assay			Tested for inhibition of cholesterol biosynthesis in HEP G2 cells, IC50=0.029μM.	7932551
HEP-G2	Function assay			Tested for ability to inhibit incorporation of [14C]acetate into cholesterol in cultured human hepatoma (HEP-G2) cells; 0.061-0.10, IC50=0.079μM.	8246237
3T3-G185	Function assay			TP_TRANSPORTER: inhibition of Daunorubicin transport in 3T3-G185 cells, IC50=26μM.	11474784
NIH-3T3-G185	Function assay			TP_TRANSPORTER: inhibition of LDS-751 efflux in NIH-3T3-G185 cells, IC50=32.7μM.	11716514
MDCK	Function assay			TP_TRANSPORTER: inhibition of calcein-AM efflux in MDR1-expressing MDCK cells, IC50=10μM.	15616150
HEK293	Function assay			TP_TRANSPORTER: inhibition of estradiol-17beta-glucuronide uptake(estradiol-17beta-glucuronide:0.02uM) in OATP1B1-expressing HEK293 cells, IC50=28μM.	15616150
Huh-7/3-1	Antiviral assay		72 hrs	Antiviral activity against Hepatitis C virus (isolate Con1) genotype 1b in human Huh-7/3-1 cells assessed as inhibition of HCV replication after 72 hrs by luciferase assay	16408072
SW480	Growth inhibition assay		96 hrs	Growth inhibition of human SW480 cells after 96 hrs by MTS assay, IC50=7.1μM.	17472962
LS180	Growth inhibition assay		96 hrs	Growth inhibition of human LS180 cells after 96 hrs by MTS assay, IC50=25.3μM.	17472962
HT29	Growth inhibition assay		96 hrs	Growth inhibition of human HT29 cells after 96 hrs by MTS assay, IC50=46.8μM.	17472962
SW480	Growth inhibition assay	20 uM	48 hrs	Reversal of growth inhibition of human SW480 cells at 20 uM after 48 hrs by MTS assay in presence of >50 uM mevalonate	17472962
SW480	Function assay	20 uM	48 hrs	Decrease in survivin expression in human SW480 cells at 20 uM after 48 hrs by immunoblot analysis	17472962
SW480	Function assay	20 uM	48 hrs	Reversal of reduction in survivin expression in human SW480 cells at 20 uM after 48 hrs by immunoblot analysis in presence of 100 uM mevalonate	17472962
SW480	Function assay	20 uM	48 hrs	Reversal of reduction in survivin mRNA expression in human SW480 cells at 20 uM after 48 hrs by RT-PCR technique in presence of 100 uM mevalonate	17472962
LS180	Function assay	20 uM		Inhibition of survivin expression in parent human LS180 cells at 20 uM by immunoblot analysis	17472962
LS180	Function assay	20 uM		Inhibition of survivin expression in survivin gene transfected human LS180 cells at 20 uM immunoblot analysis	17472962
SW480	Growth inhibition assay	20 uM	48 hrs	Reversal of growth inhibition of human SW480 cells at 20 uM after 48 hrs by immunoblot analysis in presence of farnesyl pyrophosphate	17472962
SW480	Growth inhibition assay	20 uM	48 hrs	Reversal of growth inhibition of human SW480 cells at 20 uM after 48 hrs by immunoblot analysis in presence of geranylgeranyl pyrophosphate	17472962
SW480	Function assay	20 uM	48 hrs	Decrease in isoprenylated Ras level in human SW480 cells at 20 uM after 48 hrs by immunoblot analysis	17472962
SW480	Function assay	20 uM	48 hrs	Reversal of decrease in isoprenylated Ras level in human SW480 cells at 20 uM after 48 hrs by immunoblot analysis in presence of mevalonate	17472962
SW480	Function assay	20 uM	48 hrs	Reversal of decrease in isoprenylated Ras level in human SW480 cells at 20 uM after 48 hrs by immunoblot analysis in presence of farnesyl pyrophosphate	17472962
SW480	Function assay	20 uM	48 hrs	Reversal of decrease in isoprenylated Ras level in human SW480 cells at 20 uM after 48 hrs by immunoblot analysis in presence of geranylgeranyl pyrophosphate	17472962
SW480	Function assay	20 uM		Inhibition of FBS-stimulated increase in Ras protein expression in human SW480 cells assessed as GTP-bound protein at 20 uM by immunoblot analysis	17472962
SW480	Function assay	20 uM		Reversal of inhibition of FBS-stimulated increase in Ras protein expression in human SW480 cells assessed as GTP-bound protein at 20 uM by immunoblot analysis	17472962
SW480	Function assay	20 uM		Inhibition of FBS-stimulated increase in Akt phosphorylation in human SW480 cells at 20 uM by immunoblot analysis	17472962
LS180	Growth inhibition assay		72 hrs	Blockade of growth inhibition of human LS180 cells after 72 hrs by MTS method	17472962
K562	Function assay		48 hrs	Inhibition of GGTase1 in human K562 cells assessed as reduction of Rap1a protein geranylgeranylation after 48 hrs by Western blotting	20832326
A549	Cytotoxicity assay		72 hrs	Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50=11.4μM.	23570542
A549	Function assay		5 mins	Inhibition of HMG-CoA reductase in human A549 cells after 5 mins by spectrophotometric analysis, IC50=19.8μM.	23570542
HS68	Cytotoxicity assay		72 hrs	Cytotoxicity against human HS68 cells after 72 hrs by MTT assay, IC50=23.2μM.	23570542
MEF	Cytotoxicity assay		72 hrs	Cytotoxicity against mouse MEF cells after 72 hrs by MTT assay, IC50=35μM.	23570542
MDA-MB-231	Function assay	1 to 10 uM	24 hrs	Induction of p21 expression in human PR, ER, HER2-negative human MDA-MB-231 cells at 1 to 10 uM after 24 hrs by western blot analysis	24556504
MDA-MB-361	Growth inhibition assay		48 hrs	Growth inhibition of ER-positive, HER2-positive human MDA-MB-361 cells after 48 hrs by WST-1 assay	24556504
MDA-MB-468	Growth inhibition assay		48 hrs	Total growth inhibition of PR, ER, HER2-negative human MDA-MB-468 cells after 48 hrs by WST-1 assay	24556504
AU565	Growth inhibition assay		48 hrs	Growth inhibition of ER-negative, HER2-positive human AU565 cells after 48 hrs by WST-1 assay	24556504
MCF7	Growth inhibition assay		48 hrs	Total growth inhibition of ER-positive, HER2-negative human MCF7 cells after 48 hrs by WST-1 assay	24556504
MDA-MB-231	Growth inhibition assay	>10 uM	48 hrs	Total growth inhibition of PR, ER, HER2-negative human MDA-MB-231 cells at >10 uM after 48 hrs by WST-1 assay	24556504
RPMI-8226	Function assay	10 uM	48 hrs	Inhibition of HMG-coA reductase in human RPMI-8226 cells assessed as disruption of Rap1a geranylgeranylation at 10 uM after 48 hrs by western blot analysis	24726306
HepG2	Function assay	1 uM	6 hrs	Lipid-lowering effect in human HepG2 cells assessed as reduction in oleic acid-induced lipid accumulation at 1 uM after 6 hrs by oil-red O staining based spectrophotometry	25304895
HepG2	Function assay	10 uM	24 hrs	Lipid-lowering effect in human HepG2 cells assessed as reduction in oleic acid-induced total cholesterol accumulation at 10 uM after 24 hrs by oil-red O staining based spectrophotometry	25304895
HepG2	Function assay	10 uM	24 hrs	Lipid-lowering effect in human HepG2 cells assessed as reduction in oleic acid-induced triglyceride accumulation at 10 uM after 24 hrs by oil-red O staining based spectrophotometry	25304895
RPMI8226	Apoptosis assay	20 uM	48 hrs	Induction of apoptosis in human RPMI8226 cells assessed as increase in PARP cleavage at 20 uM incubated for 48 hrs by immunoblot method	25935643
RPMI8226	Apoptosis assay	20 uM	48 hrs	Induction of apoptosis in human RPMI8226 cells assessed as increase in caspase-3 cleavage at 20 uM incubated for 48 hrs by immunoblot method	25935643
HepG2	Function assay		6 hrs	Lipid lowering activity in human HepG2 cells assessed as decrease in oleic acid elicited lipid accumulation after 6 hrs by oil-red O staining method, IC50=8.3μM.	26169125
A549	Antiviral assay		48 hrs	Antiviral activity against Dengue virus 2 NGC infected in human A549 cells assessed as reduction in virus replication after 48 hrs by renilla luciferase reporter gene assay, EC50=1.82μM.	26771861
Neuro2a	Function assay	1 uM		Inhibition of HMGCoA reductase in Dhcr7-deficient mouse Neuro2a cells assessed as decrease in 7-DHC levels at 1 uM by LC-MS/GC-MS analysis	26789657
Vero	Cytotoxicity assay			Cytotoxicity against African green monkey Vero cells, IC50=2.2μM.	27228159
KB	Cytotoxicity assay			Cytotoxicity against human KB cells by resazurin microplate assay, IC50=15.6μM.	27228159
PC3	Cytotoxicity assay		48 hrs	Cytotoxicity against human PC3 cells assessed as growth inhibition after 48 hrs by SRB assay, IC50=5.4μM.	27756564
MDA-MB-231	Function assay	30 uM	24 hrs	Induction of reactive oxygen species in human MDA-MB-231 cells at 30 uM after 24 hrs by DCFH-DA probe-based flow cytometric method	27756564
MDA-MB-231	Function assay	10 uM	6 to 24 hrs	Induction of CHK1/2 phosphorylation in human MDA-MB-231 cells assessed as increase in p53 phosphorylation at 10 uM after 6 to 24 hrs by Western blot method	27756564
MDA-MB-231	Function assay	10 uM	6 to 24 hrs	Induction of ATM phosphorylation in human MDA-MB-231 cells at 10 uM after 6 to 24 hrs by Western blot method	27756564
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
RPMI8226	Function assay	0.5 uM	48 hrs	Inhibition of FTase in human RPMI8226 cells assessed as disruption of H-ras farnesylation at 0.5 uM after 48 hrs by immunoblot analysis	31699606
RPMI8226	Function assay	0.5 uM	48 hrs	Inhibition of GGtase-1 in human RPMI8226 cells assessed as disruption of Rap1a geranylgeranylation at 0.5 uM after 48 hrs by immunoblot analysis	31699606
A549	Function assay			Reductase Activity Assay: The HMGR activity was performed using HMG-CoA reductase assay kit from Sigma-Aldrich with the human recombinant protein or 100 μg total cell lysates from A549 cells. Lovastatin was used as a positive control, IC50=0.0295μM.	ChEMBL
HepG2	Function assay			Compound was evaluated for inhibitory activity against HMG-CoA reductase in HepG2 cells, IC50=0.039μM.	ChEMBL
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Chemische informatie, opslag en stabiliteit

Molecuulgewicht	404.54	Formule	C₂₄H₃₆O₅	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	75330-75-5	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	Mevinolin, MK-803			Smiles	CCC(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC3CC(CC(=O)O3)O)C

Oplosbaarheid

In vitro
Batch:

DMSO : 80 mg/mL (197.75 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 35 mg/mL

Water : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	2.500mg/ml (6.18mM)	Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Targets/IC₅₀/Ki	HMG-CoA reductase (Cell-free assay) 3.4 nM
In vitro	Lovastatin remt de LPS- en cytokine-gemedieerde productie van NO en de expressie van iNOS in primaire rat-astrocyten. Deze verbinding remt de LPS-geïnduceerde expressie van TNF-alpha, IL-1beta en IL-6 in primaire rat-astrocyten, microglia en macrofagen. Dit chemische middel resulteert in meer dan 95% remming van DNA-synthese gemeten door incorporatie van [3H]thymidine in DNA. Het synchroniseert cellen in de G1-fase en niet in de G0-fase van de celcyclus. Het heeft een vergelijkbare groeiremmende activiteit tegen zowel ras-afhankelijke als ras-onafhankelijke cellijnen. Dit middel produceert een diepgaande reductie van apolipoproteïne-B-bevattende lipoproteïnen, met name LDL-cholesterol en, in mindere mate, plasmatriglyceriden, en een kleine toename van HDL-cholesterol. Het arresteert cellen door het proteasoom te remmen, wat resulteert in de accumulatie van p21 en p27, leidend tot G1-arrest. Deze verbinding is een remmer van hydroxymethylglutaryl (HMG)-CoA Reductase, het snelheidsbepalende enzym in de cholesterolsynthese. Het kan worden gebruikt om gekweekte cellen in de G1-fase van de celcyclus te arresteren, wat resulteert in de stabilisatie van de cycline-afhankelijke kinase-remmers (CKI's) p21 en p27. Deze chemische stof (2-10 mM) arresteert cellen in G1 en verlengde – of arresteerde een minoritaire fractie van cellen in – de G2-fase van de celcyclus in de menselijke blaascarcinoom T24-cellijn die geactiveerd p21ras tot expressie brengt. Het (50 mM) is cytotoxisch in de menselijke blaascarcinoom T24-cellijn die geactiveerd p21ras tot expressie brengt.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/9389730/ [2] https://pubmed.ncbi.nlm.nih.gov/1711413/ [3] https://pubmed.ncbi.nlm.nih.gov/12815379/ [4] https://pubmed.ncbi.nlm.nih.gov/10393901/ [5] https://pubmed.ncbi.nlm.nih.gov/1673788/ [6] https://pubmed.ncbi.nlm.nih.gov/31037159/

Toepassingen

Methoden	Biomarkers	PMID
Western blot	HMGR p-AKT / AKT / p-GSK3β / GSK3β / p-β-catenin / β-catenin / TAZ	17412884
Immunofluorescence	β-catenin	30975976
Growth inhibition assay	Cell viability	20205716

Informatie over klinische proeven

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT01478828	Terminated	Prostate Cancer	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins\|Patrick C Walsh Prostate Cancer Research Fund	July 13 2012	Not Applicable
NCT01527669	Completed	Healthy Subjects	National Taiwan University Hospital\|National Science Council Taiwan	February 2012	Phase 4
NCT01385020	Completed	Healthy Subjects	National Taiwan University Hospital\|National Science Council Taiwan	July 2011	Phase 4
NCT00700921	Completed	Chronic Obstructive Pulmonary Disease (COPD)	National Jewish Health\|National Heart Lung and Blood Institute (NHLBI)	April 2008	Phase 2

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