Name: Simvastatin (MK-733)
Brand: Selleck Chemicals
SKU: S1792
Rating: 5 (80 reviews)

Saltar a

Control de calidad (Quality Control)

Lote: Pureza: 99.92%

99.92

Dianas relacionadas	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism
Otros HMG-CoA Reductase Inhibidores	Mevastatin SR-12813 Clinofibrate Dihydrolanosterol 7-ketocholesterol Cerivastatin sodium

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Descripción de la actividad
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
Haga clic para ver más datos experimentales de líneas celulares

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	418.57	Fórmula	C₂₅H₃₈O₅	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	79902-63-9	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	MK 733			Smiles	CCC(C)(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC3CC(CC(=O)O3)O)C

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 83 mg/mL (198.29 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 83 mg/mL

Water : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
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 Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	4.150mg/ml (9.91mM)	Taking the 1 mL working solution as an example, add 50 μL of 83 mg/ml clear DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween-80 to the above system, mix evenly to clarify it; Then continue to add 500 μL 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.

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH₂O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción (Mechanism of Action)

Targets/IC₅₀/Ki	HMG-CoA reductase (Cell-free assay) 0.1-0.2 nM(Ki)
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%.
Ensayo de quinasa	Ensayo de actividad de la HMG-CoA Reductase
Ensayo de quinasa	El volumen total de cada ensayo es de 95 μL y la mezcla de reacción contenía 10 μL del compuesto inhibidor a analizar y 85 μL de tampón de incubación que contiene 2 mg/mL de microsomas hepáticos, 0,1 M KH₂PO₄, pH 7,2, 5,7 mM de ditiotreitol, 10 mM de glucosa-6-fosfato, 2 U/mL de glucosa-6-fosfato deshidrogenasa, 1 mM de NADP, 10 μM de miconazol. Los experimentos de control se realizan sin sistema generador de NADPH. Todas las muestras se incuban 10 min a 37 ℃ antes de añadir 5 μL de sustrato (sin marcar y 14C-HMG-3-hydroxy-3-methyl glutaryl CoA, concentración final 50 μM, 2,5 nCi/nmole). Después de 30 min a 37 ℃, la reacción se detiene añadiendo 27 μL de HCl 1N y 20 μL de mevalonolactona sin marcar (200 μg/ensayo). La conversión de ácido mevalónico a lactona se realiza a temperatura ambiente durante 60 min.
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.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/3076125/ [2] https://pubmed.ncbi.nlm.nih.gov/10973320/ [3] https://pubmed.ncbi.nlm.nih.gov/12538717/ [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/

Aplicaciones (Applications)

Métodos	Biomarcadores	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

Información del ensayo clínico (Clinical Trial Information)

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
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

Preguntas frecuentes (Frequently Asked Questions)

Pregunta 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?

Respuesta:
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.

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

Respuesta:
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/.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Simvastatin (MK-733) HMG-CoA Reductase inhibitor

Estructura química

Peso molecular: 418.57

Control de calidad (Quality Control)

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Solubilidad (Solubility)

Calculadora de Molaridad

Calculadora de formulación in vivo (Solución clara)

Mecanismo de acción (Mechanism of Action)

Aplicaciones (Applications)

Información del ensayo clínico (Clinical Trial Information)

Preguntas frecuentes (Frequently Asked Questions)

Simvastatin (MK-733) HMG-CoA Reductase inhibitor

Estructura química

Peso molecular: 418.57

Control de calidad (Quality Control)

Cultivo celular, tratamiento y concentración de trabajo (Cell Culture, Treatment & Working Concentration)

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Solubilidad (Solubility)

Calculadora de Molaridad

Calculadora de formulación in vivo (Solución clara)

Mecanismo de acción (Mechanism of Action)

Aplicaciones (Applications)

Información del ensayo clínico (Clinical Trial Information)

Preguntas frecuentes (Frequently Asked Questions)

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)