Name: Selisistat (EX-527)
Brand: Selleck Chemicals
SKU: S1541
Rating: 5 (321 reviews)

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Control de calidad (Quality Control)

Lote: Pureza: 99.78%

99.78

Dianas relacionadas	HDAC JAK BET Histone Methyltransferase PKC PARP HIF PRMT EZH2 AMPK
Otros Sirtuin Inhibidores	SRT 1720 Hydrochloride Sirtinol Fisetin 3-TYP AGK2 SRT2104 (GSK2245840) OSS_128167 SirReal2 SRT2183 Thiomyristoyl

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

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Formulación	Descripción de la actividad	PMID
Platelets	Apoptosis Assay	10/50 μM	10 min	DMSO	increases ROS level in a dose-dependent manner	25829495
HEK 293	Growth Inhibition Assay		24 h		IC50=97.7 ± 8.1 μM	24998427
HeLa	Growth Inhibition Assay		24 h		IC50=37.9 ± 1.8 μM	24998427
HEK 293	Growth Inhibition Assay		48 h		IC50=69.0 ± 0.7 μM	24998427
HeLa	Growth Inhibition Assay		48 h		IC50=8.9 ± 1.9 μM	24998427
RMECs	Apoptosis Assay	10 μM	24 h		attenuates the anti-apoptotic effect of Des-G	24486147
HUVECs	Apoptosis Assay	10 μM	24 h		bolishes the protective effect of resveratrol in cell viability	23358928
K562	Function Assay	0.1-1 μM	2 h		stimulates Nrf2-dependent gene transcription	21196497
INS-1E	Function Assay	1 μm	24 h		prevents resveratrol-induced up-regulation of Glut2, glucokinase,Pdx-1, and Tfam	21163946
MCF-7	Growth Inhibition Assay	0-100 μM	24/48/72 h	DMSO	represses cell proliferation at the concentration ≥100 μM	20371709
NCI-H460	Function Assay	1 μm	6 h	DMSO	produces a concentration-dependent increase in the amount of acetylated p53	16354677
293T	Function assay				Inhibition of human recombinant GST-tagged SIRT1 expressed in 293T cells by Fluor de Lys fluorescence assay, IC50 = 0.038 μM.	21306906
Escherichia coli cells	Function assay				Inhibition of human recombinant SIRT1 expressed in Escherichia coli cells using acetylated Lys side chain amino acids 379-382 (Arg-His-Lys-Lys(Ac)) p53 conjugated with aminomethylcoumarin as substrate by fluorescence assay, IC50 = 0.16 μM.	22931526
BL21 (DE3)	Function assay				Inhibition of full length human SIRT1 expressed in Escherichia coli BL21 (DE3) cells using fluorogenic 7-amino-4-methylcoumarin (AMC)-labeled peptide by fluorescence assay, IC50 = 0.21 μM.	25275824
Namalwa cells	Function assay		3 hrs		Inhibition of SIRT1-mediated endogenous p53 deacetylase activity in human Namalwa cells assessed as concentration required to enhance p53 deacetylation to twice the basal level after 3 hrs by ELISA, INH = 0.6 μM.	25971769
BL21 (DE3)	Function assay				Inhibition of full length human SIRT2 expressed in Escherichia coli BL21 (DE3) cells using fluorogenic 7-amino-4-methylcoumarin (AMC)-labeled peptide by fluorescence assay, IC50 = 1.94 μM.	25275824
Escherichia coli cells	Function assay				Inhibition of human recombinant SIRT2 expressed in Escherichia coli cells using acetylated Lys side chain amino acids 379-382 (Arg-His-Lys-Lys(Ac)) p53 conjugated with aminomethylcoumarin as substrate by fluorescence assay, IC50 = 48.5 μM.	22931526
A673	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
Hs683	Cell cycle assay		24 to 48 hrs		Cell cycle arrest in human Hs683 cells assessed as accumulation at G1 phase at IC50 after 24 to 48 hrs by propidium iodide staining-based flow cytometry	28475330
HCT116	Function assay	10 uM	8 hrs		Inhibition of SIRT1 in human HCT116 cells assessed as increase in acetylated p53 at 10 uM after 8 hrs by Western blot analysis	22642300
NCI-H460	Function assay		6 hrs		Inhibition of SIRT-2 in human NCI-H460 cells assessed as inhibition of p53 deacetylation after 6 hrs by immunoprecipitation/immunoblotting analysis, IC50 = 1 μM.	ChEMBL
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	248.71	Fórmula	C₁₃H₁₃ClN₂O	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	49843-98-3	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	SEN0014196			Smiles	C1CC(C2=C(C1)C3=C(N2)C=CC(=C3)Cl)C(=O)N

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 300 mg/mL (1206.22 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 30 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.	2.000mg/ml (8.04mM)	Taking the 1 mL working solution as an example, add 50 μL of 40 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 clarify; 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.
Clear solution	5%DMSO 1 Corn oil Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	3.000mg/ml (12.06mM)	Taking the 1 mL working solution as an example, add 50 μL of 60 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
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.	3.000mg/ml (12.06mM)	Taking the 1 mL working solution as an example, add 50 μL of 60 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 clarify; 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.

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)

Características	Greater potency, specificity, stability, and lower toxicity than other inhibitors of SIRT1 catalytic activity identified to date.
Targets/IC₅₀/Ki	SIRT1 (Cell-free assay) 38 nM
In vitro	Selisistat (EX 527) exhibits a potently inhibitory effect against SIRT1 deacetylase activity in a concentration-dependent manner with an IC50 of 38 nM, and displays much lower activity against SIRT2 and SIRT3 with IC50 values of 19.6 μM and 48.7 μM, respectively. It does not inhibit SIRT4-7 and class I/II HDAC activity at concentrations up to 100 μM. This compound alone (1 μM) has no detectable effect on the acetylation of p53 lysine 382 in NCI-H460 cells, but significantly increases the amount of acetylated p53 in NCI-H460 cells, human mammary epithelial cells, U-2 OS and MCF-7 cells subjected to genotoxic agents Hydrogen peroxide, which is more effective than that caused by Nicotinamide (5 mM). Surprisingly, it does not result in detectable effects on p53-controled gene expression, cell survival, or cell proliferation. It causes a 90% increase in cell number of HCT116 cells after 7 days in the condition of 0.1% serum but not 10% serum, suggesting that SIRT1 is a significant regulator of cell proliferation during growth factor deprivation conditions. Additionally, it abrogates resveratrol effects on glucose responses, and prevents resveratrol-induced up-regulation of Glut2, glucokinase, Pdx-1, and Tfam in INS-1E Cells, due to the opposite effect of EX 527 and resveratrol on SIRT1 deacetylase activity.
Ensayo de quinasa	Inhibición de la actividad desacetilasa de GST-SIRT1
Ensayo de quinasa	Las células 293T se transfectan transitoriamente con SIRT1 humano marcado con GST en el vector pDEST27 Gateway usando FuGENE-6. Después de 48 horas, las células se lisan con 50 mM Tris, pH 8,0, 120 mM NaCl, 1 mM EDTA y 0,5 % de Nonidet P-40, suplementado con tabletas de cóctel de inhibidores de proteasa Complete Mini. La GST-SIRT1 se purifica de los lisados y se lava extensamente en el tampón anterior. El ensayo de desacetilación se realiza con aproximadamente 30 ng de GST-SIRT1 en presencia de Selisistat (EX 527) (48 pM a 100 μM). La desacetilación se mide usando el kit Fluor de Lys empleando un péptido fluorogénico que abarca los residuos 379 a 382 de p53, acetilado en la lisina 382. El residuo de lisina acetilado se acopla a una porción de aminometilcumarina. El péptido es desacetilado por SIRT1, seguido de la adición de un revelador proteolítico que libera la aminometilcumarina fluorescente. Brevemente, las preparaciones enzimáticas se incuban con 170 μM de NAD⁺ y 100 μM de péptido fluorogénico p53 durante 45 minutos a 37 °C, seguido de incubación en el revelador durante 15 minutos a 37 °C. La fluorescencia se mide por excitación a 360 nm y emisión a 460 nm y la actividad enzimática se expresa en unidades de fluorescencia relativa.
In vivo	Administration of Selisistat (EX 527; ~10 μg) to rats increases hypothalamic acetyl-p53 levels by inhibiting hypothalamic SIRT1 activity. Co-administration of this compound with ghrelin markedly blunts the orexigenic action of ghrelin by decreasing the pAMPK levels, increasing the ACC levels, and abolishing the higher expression of the transcription factors FoxO1, pCREB, and Bsx and the neuropeptides NPY and AgRP in the hypothalamic arcuate nucleus.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/16354677/ [2] https://pubmed.ncbi.nlm.nih.gov/19433578/ [3] https://pubmed.ncbi.nlm.nih.gov/21163946/ [4] https://pubmed.ncbi.nlm.nih.gov/21386086/

Aplicaciones (Applications)

Métodos	Biomarcadores	PMID
Western blot	GRP78 / FASL / Bcl-2 / LC3 Ac-H3K9 / Fibronectin / Collagen 1 / α-SMA PCNA / Cyclin D1 / Cyclin E pEGFR / EGFR / pPDGFRβ / PDGFRβ pSTAT3 / STAT3 p27 FOXO3a / SIRT1 / Ac-p53 / p16(INK4a)	29312612
Immunofluorescence	p-p38	26824501
Growth inhibition assay	Cell viability	24484175

Información del ensayo clínico (Clinical Trial Information)

(datos de https://clinicaltrials.gov, actualizado el 2021-11-17)

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
NCT04184323	WITHDRAWN	Endometriosis; Uterine Diseases; Endometrial Diseases; Infertility Unexplained; Infertility; Female, Nonimplantation	Wake Forest University Health Sciences	2022-01	PHASE2
NCT01485965	Completed	Huntington''s Disease	Siena Biotech S.p.A.	2011-11	Phase 1
NCT01521832	Completed	Huntington''s Disease	Siena Biotech S.p.A.	2009-10	Phase 1

Preguntas frecuentes (Frequently Asked Questions)

Pregunta 1:
what is the extinction coefficient of it?

Respuesta:
Its extinction coefficient is 1421.650635.

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):

Selisistat (EX-527) inhibidor de SIRT1

Peso molecular: 248.71

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)

Selisistat (EX-527) inhibidor de SIRT1

Peso molecular: 248.71

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)