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

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

N. Cat.S2061

La Lovastatin è un inibitore della HMG-CoA reduttasi con IC50 di 3,4 nM in un saggio acellulare, utilizzato per abbassare il colesterolo (agente ipolipemizzante). La Lovastatin innesca l'autophagy.

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

Struttura chimica

Peso molecolare: 404.54

Vai a

Controllo Qualità

Lotto: Purezza: 99.99%

99.99

Target correlati	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism
Altro HMG-CoA Reductase Inibitori	Mevastatin SR-12813 Clinofibrate Dihydrolanosterol 7-ketocholesterol Cerivastatin sodium

Coltura cellulare, trattamento e concentrazione di lavoro

Linee cellulari	Tipo di saggio	Concentrazione	Tempo di incubazione	Descrizione dellattività	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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Informazioni chimiche, conservazione e stabilità

Peso molecolare	404.54	Formula	C₂₄H₃₆O₅	Conservazione (Dalla data di ricezione)	3 anni-20°Cpolvere
N. CAS	75330-75-5	Scarica SDF		Conservazione delle soluzioni stock	1 anno-80°Cin solvente 1 mese-20°Cin solvente
Sinonimi	Mevinolin, MK-803			Smiles	CCC(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC3CC(CC(=O)O3)O)C

Solubilità

In vitro
Lotto:

DMSO : 80 mg/mL (197.75 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Ethanol : 35 mg/mL

Water : Insoluble

Calcolatore di Molarità

Massa	Concentrazione	Volume	Peso molecolare
=	×	×

Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo Lotto:
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 Validato dai laboratori Selleck. Se necessiti di modifiche a questa formulazione, contatta il nostro team di vendita per test personalizzati.	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.

Calcolatore di formulazione in vivo (Soluzione chiara)

Passo 1: Inserire le informazioni di seguito (Consigliato: Un animale aggiuntivo per tenere conto della perdita durante lesperimento)

Dosaggio: mg/kg Peso medio degli animali: g Volume di dosaggio per animale:μL Numero di animali:

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non cè una formulazione in vivo nella sezione Solubilità.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Risultati del calcolo:

Concentrazione di lavoro: mg/ml;

Metodo per preparare il liquido master di DMSO: mg farmaco predissolto in μL DMSO ( Concentrazione del liquido master mg/mL, Vi preghiamo di contattarci prima se la concentrazione supera la solubilità del DMSO del lotto del farmaco. )

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungereμL PEG300, mescolare e chiarire, quindi aggiungereμL Tween 80, mescolare e chiarire, quindi aggiungere μL ddH₂O, mescolare e chiarire.

Metodo per preparare la formulazione in vivo: Prendere μL DMSO liquido master, quindi aggiungere μL Olio di mais, mescolare e chiarire.

Nota: 1. Si prega di assicurarsi che il liquido sia limpido prima di aggiungere il solvente successivo.
2. Assicurarsi di aggiungere il/i solvente/i in ordine. È necessario assicurarsi che la soluzione ottenuta, nellaggiunta precedente, sia una soluzione limpida prima di procedere allaggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno dacqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo dazione

Targets/IC₅₀/Ki	HMG-CoA reductase (Cell-free assay) 3.4 nM
In vitro	Lovastatin inibisce la produzione di NO mediata da LPS e citochine e l'espressione di iNOS negli astrociti primari di ratto. Questo composto inibisce l'espressione indotta da LPS di TNF-alpha, IL-1beta e IL-6 negli astrociti primari, nella microglia e nei macrofagi di ratto. Questa sostanza chimica provoca oltre il 95% di inibizione della sintesi del DNA, misurata dall'incorporazione di [3H]timidina nel DNA. Sincronizza le cellule nella fase G1 e non nella fase G0 del ciclo cellulare. Ha un'attività inibitoria della crescita simile contro le linee cellulari sia dipendenti che indipendenti da ras. Questo agente produce una profonda riduzione delle lipoproteine contenenti apolipoproteina B, in particolare il colesterolo LDL e, in misura minore, i trigliceridi plasmatici, e un piccolo aumento del colesterolo HDL. Arresta le cellule inibendo il proteasoma, il che si traduce nell'accumulo di p21 e p27, portando all'arresto in G1. Questo composto è un inibitore della idrossimetil glutaril (HMG)-CoA reduttasi, l'enzima limitante della sintesi del colesterolo. Può essere usato per arrestare le cellule in coltura nella fase G1 del ciclo cellulare, con conseguente stabilizzazione degli inibitori delle chinasi ciclina-dipendenti (CKI) p21 e p27. Questa sostanza chimica (2-10 mM) arresta le cellule in G1 e ha anche prolungato – o arrestato una frazione minore di cellule in – la fase G2 del ciclo cellulare nella linea cellulare di carcinoma della vescica umana T24 che esprime p21ras attivato. Essa (50 mM) è citotossica nella linea cellulare di carcinoma della vescica umana T24 che esprime p21ras attivato.
Riferimenti	[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/

Applicazioni

Metodi	Biomarcatori	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

Informazioni sullo studio clinico

(dati da https://clinicaltrials.gov, aggiornato il 2024-05-22)

Numero NCT	Reclutamento	Condizioni	Sponsor/Collaboratori	Data di inizio	Fasi
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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