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SRT 1720 Hydrochloride Attivatore di SIRT1

N. Cat.: S1129

SRT1720 HCl è un attivatore selettivo di SIRT1 con EC50 di 0,16 μM in un saggio cell-free, ma è >230 volte meno potente per SIRT2 e SIRT3. SRT1720 induce l'autofagia.
SRT 1720 Hydrochloride Sirtuin Attivatore Chemical Structure

Struttura chimica

Peso molecolare: 506.02

Vai a

Controllo Qualità (Quality Control)

Lotto: Purezza: 99.61%
99.61

Prodotti spesso usati con SRT 1720 Hydrochloride

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Quercetin (Sophoretin)

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Astragaloside IV

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MDL-28170

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Coltura cellulare, trattamento e concentrazione di lavoro
(Cell Culture, Treatment & Working Concentration)

Linee cellulari Tipo di saggio Concentrazione Tempo di incubazione Formulazione Descrizione dell'attività PMID
CACs  Function Assay 4 μM 30 min DMSO induces acute SIRT1 activation  26254104
MC3T3-E1 Function Assay 10 µM  1 h reduces the TGF-β-stimulated VEGF release in dose- and time-dependent manner  26136978
MC3T3-E1 Function Assay 10 µM  12 h reduces the VEGF mRNA expression levels stimulated by TGF-β 26136978
MC3T3-E1 Function Assay 20 μM 1 h suppresses the TGF-β-induced phosphorylation of p44/p42 MAP kinase or SAPK/JNK 26136978
WE-68 Apoptosis Assay 0-24 μM 24 h induces cell death in dose dependently 26055805
SK-ES-1 Apoptosis Assay 0-10 μM 24 h induces cell death in dose dependently 26055805
SK-N-MC  Apoptosis Assay 0-2.5 μM 24 h induces cell death in dose dependently 26055805
WE-68 Function Assay 20 μM 0-24 h activates caspase 3/7 26055805
SK-ES-1 Function Assay 10 μM 0-24 h activates caspase 3/7 26055805
SK-N-MC  Function Assay 3 μM 0-24 h activates caspase 3/7 26055805
NRK-49F Function Assay 0–2 μM 36 h increases expression of α-SMA and fibronectin dose dependently 26022003
NRK-49F Function Assay 0–2 μM 36 h enhances phosphorylation of EGFR and PDGFRβ  26022003
NRK-49F Function Assay 0–2 μM 36 h enhances STAT3 phosphorylation 26022003
RAW264.7 Function Assay 1 μM 6 h upregulates the reduced SIRT1 protein or mRNA levels by high glucose 25793995
MCF10A Growth Inhibition Assay 0-20 μM 24 h reduces cell viability dose dependently 25411356
MCF-7 Growth Inhibition Assay 0-20 μM 24 h reduces cell viability dose dependently 25411356
T47D Growth Inhibition Assay 0-20 μM 24 h reduces cell viability dose dependently 25411356
SKBR3 Growth Inhibition Assay 0-20 μM 24 h reduces cell viability dose dependently 25411356
MDA-MB-231 Growth Inhibition Assay 0-20 μM 24 h reduces cell viability dose dependently 25411356
SUM149 Growth Inhibition Assay 0-20 μM 24 h reduces cell viability dose dependently 25411356
HS578T Growth Inhibition Assay 0-20 μM 24 h reduces cell viability dose dependently 25411356
BT20 Growth Inhibition Assay 0-20 μM 24 h reduces cell viability dose dependently 25411356
A459 Growth Inhibition Assay 0-20 μM 24 h reduces cell viability dose dependently 25411356
HCT116 Growth Inhibition Assay 0-20 μM 24 h reduces cell viability dose dependently 25411356
Neu Growth Inhibition Assay 0-20 μM 24 h reduces cell viability dose dependently 25411356
MDA-MB-231 Function Assay 5 μM 8 h increases the number of acidic vesicular organelles 25411356
MDA-MB-231 Function Assay 5 μM 16 h induces lysosomal membrane permeabilization 25411356
MC3T3-E1 Function Assay 10 μM 60 min  suppresses the FGF-2-stimulated osteoprotegerin release 25290095
MC3T3-E1 Function Assay 10 μM 60 min  attenuates the FGF-2-induced osteoprotegerin mRNA expression 25290095
MC3T3-E1 Function Assay 10 μM 60 min  attenuates the FGF-2-induced osteoprotegerin mRNA expression 25290095
MC3T3-E1 Function Assay 10 μM 60 min  suppresses the BMP-4-stimulated VEGF release 24435444
MC3T3-E1 Function Assay 10 μM 60 min  suppresses the PGF2α-stimulated OPG release 24333336
MC3T3-E1 Function Assay 10 μM 60 min  reduces the PGF2α-stimulated phosphorylation of p44/p42 MAP kinase 24333336
MC3T3-E1 Function Assay 10 μM 60 min  attenuates the PGF2α-induced phosphorylation of both MEK1/2 and Raf-1 24333336
RPE Cell Viability Assay 5 µM 1 h attenuates OAβ-induced decrease of cell viability 24036938
9607 Cell Viability Assay 1 μM 36 h increases the cell viability compared with melatonin alone 23726949
9607 Function Assay 1 μM 36 h increases SIRT1 and decreased acetylated-p53 expression 23726949
RPMI.8226 Cell Viability Assay 7/10 μM 24 h decreases viability concentration dependently 21950728
U266 Cell Viability Assay 7/10 μM 24 h decreases viability concentration dependently 21950728
MM.1S Cell Viability Assay 7/10 μM 24 h decreases viability concentration dependently 21950728
KMS12 Cell Viability Assay 7/10 μM 24 h decreases viability concentration dependently 21950728
LR5 Cell Viability Assay 7/10 μM 24 h decreases viability concentration dependently 21950728
MM.1R Cell Viability Assay 7/10 μM 24 h decreases viability concentration dependently 21950728
Ina6 Cell Viability Assay 7/10 μM 24 h decreases viability concentration dependently 21950728
RPMI-8226 Apoptosis Assay 7/10 μM 24 h induces a significant increase in the Annexin V+/PI− apoptosis 21950728
MM.1R  Apoptosis Assay 7/10 μM 24 h induces a significant increase in the Annexin V+/PI− apoptosis 21950728
H411EC3 Function Assay 50/100 nM 6 h increases SIRT1 activity in the presence of TSA, PEPCK activity, mRNA levels of Pck1 and Pgc1α, and elevating glucose production 21212096
hepatocytes Function Assay 10 nM 6 h increases SIRT1 activity in the presence of TSA, PEPCK activity, mRNA levels of Pck1 and Pgc1α, and elevating glucose production 21212096
hepatocytes Function Assay 10 nM 6 h increases Hmgcr and Acc gene expression 21212096
U2OS Function assay 0.10 uM Activation of SIRT1 in human U2OS cells assessed as decrease in p53 deacetylation level at 0.10 uM 18046409
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD 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
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
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Informazioni chimiche, conservazione e stabilità (Chemical Information, Storage & Stability)

Peso molecolare 506.02 Formula

C25H23N7OS.HCl

 Conservazione (Dalla data di ricezione)
N. CAS 1001645-58-4 Scarica SDF Conservazione delle soluzioni stock

Sinonimi N/A Smiles C1CN(CCN1)CC2=CSC3=NC(=CN23)C4=CC=CC=C4NC(=O)C5=NC6=CC=CC=C6N=C5.Cl

Solubilità (Solubility)

In vitro
Lotto:

DMSO : 100 mg/mL (197.62 mM)
(Il DMSO contaminato da umidità può ridurre la solubilità. Utilizzare DMSO fresco e anidro.)

Water : Insoluble

Ethanol : Insoluble

Calcolatore di Molarità

Massa Concentrazione Volume Peso molecolare
Calcolatore di Diluizione Calcolatore del Peso Molecolare

In vivo
Lotto:

Calcolatore di formulazione in vivo (Soluzione chiara)

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

mg/kg g μL

Passo 2: Inserire la formulazione in vivo (Questo è solo il calcolatore, non la formulazione. Contattateci prima se non c'è 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, nell'aggiunta precedente, sia una soluzione limpida prima di procedere all'aggiunta del solvente successivo. Metodi fisici come il vortex, gli ultrasuoni o il bagno d'acqua calda possono essere utilizzati per facilitare la dissoluzione.

Meccanismo d'azione (Mechanism of Action)

Targets/IC50/Ki
SIRT1
(Cell-free assay)
0.16 μM(EC50)
In vitro

The maximum activation ratio of SRT1720 versus the closest sirtuin homologues, SIRT2 (EC1.5 = 37 μM) and SIRT3 (EC1.5 > 300 μM) is up to 781%. SRT1720 binds to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. SRT1720 could reduce fed glucose levels.  SRT1720 does not have an effect on fasting glucose in chow-fed mice, revealing that pharmacological SIRT1 activation is unlikely to induce hypoglycaemia. SRT1720 significantly reduces the hyperinsulinaemia after 4 weeks, partially normalizing increased insulin levels. SRT1720 treatment increases mitochondrial capacity by 15% in gastrocnemius muscle as measured by citrate synthase activity. Higher concentrations of SRT1720 (15 μM) induces a modest (10-20%) decrease in normal cell viability. SRT1720 also significantly inhibits VEGF-dependent MM cell migration.

Saggio chinasico
Saggio di polarizzazione della fluorescenza SIRT1
Nel saggio FP SIRT1, l'attività SIRT1 viene monitorata utilizzando un peptide di 20 aminoacidi (Ac-Glu-Glu-Lys(biotina)-Gly-Gln-Ser-Thr-Ser-Ser-His-Ser-Lys(Ac)-Nle-Ser-Thr-Glu-Gly–Lys(MR121 o Tamra)-Glu-Glu-NH2) derivato dalla sequenza di p53. Il peptide è legato N-terminalmente alla biotina e modificato C-terminalmente con un tag fluorescente. La reazione per monitorare l'attività enzimatica è un saggio enzimatico accoppiato in cui la prima reazione è la reazione di deacetilazione catalizzata da SIRT1 e la seconda reazione è la scissione da parte della tripsina al residuo di lisina appena esposto. La reazione viene interrotta e viene aggiunta streptavidina per accentuare le differenze di massa tra substrato e prodotto. La sensibilità del saggio FP consente l'identificazione di SRT1720. Le condizioni della reazione di polarizzazione della fluorescenza sono le seguenti: 0,5 μM di substrato peptidico, 150 μM di βNAD+, 0-10 nM di SIRT1, 25 mM di Tris-acetato pH 8, 137 mM di Na-Ac, 2,7 mM di K-Ac, 1 mM di Mg-Ac, 0,05% di Tween-20, 0,1% di Pluronic F127, 10 mM di CaCl 2, 5 mM di DTT, 0,025% di BSA e 0,15 mM di nicotinammide. La reazione viene incubata a 37 °C e interrotta con l'aggiunta di nicotinammide, e viene aggiunta tripsina per scindere il substrato deacetilato. Questa reazione viene incubata a 37 °C in presenza di 1 μM di streptavidina. La polarizzazione fluorescente viene determinata a lunghezze d'onda di eccitazione (650 nm) e emissione (680 nm).
In vivo

In DIO mice SRT1720 mimics several of the effects observed after calorie restriction including improved insulin sensitivity, normalized glucose and insulin levels, and increased mitochondrial capacity. In addition, in diet-induced obese and genetically obese mice, SRT1720 improves insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. Thus, SRT1720 is a promising new therapeutic agent for treating diseases of ageing such as type 2 diabetes. Consistent with improved glucose tolerance, the glucose infusion rate required to maintain euglycaemia is approximately 35% higher in SRT1720-treated fa/fa rats, and the total glucose disposal rate is increased by approximately 20%. SRT1720 also prevents multiple myeloma tumor growth. 
Riferimenti

Applicazioni (Applications)

Metodi Biomarcatori Immagini PMID
Western blot Cleaved-PARP-1 / Cleaved-caspase-3 / LC3-II / p62 / SIRT1
S1129-WB1
26655844
Immunofluorescence Cathepsin B
S1129-IF1
26655844
Growth inhibition assay Cell viability
S1129-viability1
25411356

Domande Frequenti (Frequently Asked Questions)

Domanda 1:
How can we prepare it for in vivo mouse studies?

Risposta:
It can be dissolved in 30% PEG 400+0.5% Tween 80+5% Propylene glycol at 30mg/ml as a suspension, which is fine for oral gavage. We’ve also found that it can be dissolved in 2% DMSO+30% PEG 300+1% Tween 80+ddH2O at 3mg/ml clearly, making it suitable for injection. When preparing the solution, please dissolve the compound in DMSO clearly first, then add PEG and Tween. After they are mixed well, dilute with water.