SRT1720

Catalog No.S1129

SRT1720 is a selective SIRT1 activator with EC50 of 0.16 μM in a cell-free assay, but is >230-fold less potent for SIRT2 and SIRT3.

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SRT1720 Chemical Structure

SRT1720 Chemical Structure
Molecular Weight: 506.02

Validation & Quality Control

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Product Information

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Product Description

Biological Activity

Description SRT1720 is a selective SIRT1 activator with EC50 of 0.16 μM in a cell-free assay, but is >230-fold less potent for SIRT2 and SIRT3.
Targets SIRT1 [1]
(Cell-free assay)
IC50 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. Glucose excursion during an intraperitoneal glucose tolerance test is also significantly reduced in the SRT1720 group, and comparable to rosiglitazone, a PPARγ activator that has been used to treat type 2 diabetes. 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 similar to rosiglitazone treatment. SRT1720 treatment increases mitochondrial capacity by 15% in gastrocnemius muscle as measured by citrate synthase activity. [1] 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. [2]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
CACs NIfw[3BHfW6ldHnvckBCe3OjeR?=NH;GS|Y1yqEQvF2=MXizNOKhdWmwNUn1RZFRTE2VTx?=M2L1Oolv\HWlZYOgZYN2fGViU1nSWFEh[WO2aY\heIlwdsLiNGjDNlMzPjJ3NEGwOC=>
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RPMI.8226MUTD[YxtKF[rYXLpcIl1gSCDc4PhfS=>MnjKO{8yOCEQvF2=MYOyOEBpNULzUYFl\GWlcnXhd4V{KH[rYXLpcIl1gSClb37j[Y51emG2aX;uJIRmeGWwZHXueIx6NWnT[XgyOjF7NUC3Nlg>
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MM.1R MkHNRZBweHSxc3nzJGF{e2G7M2Dr[VcwOTBizszNMnyyNlQhcA>?MmC4bY5lfWOnczDhJJNq\26rZnnjZY51KGmwY4LlZZNmKGmwIITo[UBCdm6neHnuJHYsN1CL4pkSxsBieG:ydH;zbZM>MoXjNlE6PTB5Mki=
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hepatocytesMmLPSpVv[3Srb36gRZN{[Xl?MX[xNEBvVQ>?NEXxfIw3KGh?MUDpcoNz\WG|ZYOgV2lTXDFiYXP0bZZqfHliaX6geIhmKHC{ZYPlcoNmKG:oIGTTRUwhWEWSQ1ugZYN1cX[rdImsJI1TVkFibHX2[Yx{KG:oIGDjb|Eh[W6mIGDnZ|HPuSxiYX7kJIVt\X[jdHnu[{BodHWlb4PlJJBzd2S3Y4Tpc44>NWnTS2ZlOjF{MUKwPVY>
hepatocytesMkHUSpVv[3Srb36gRZN{[Xl?MXuxNEBvVQ>?NWPOUJd4PiCqMYTpcoNz\WG|ZYOgTI1o[3MEoHHu[OKhSWOlwrDn[Y5mKGW6cILld5Nqd25?NXnFc4pWOjF{MUKwPVY>

... Click to View More Cell Line Experimental Data

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%. [1] SRT1720 also prevents multiple myeloma tumor growth. SRT1720 increases the cytotoxic activity of bortezomib or dexamethasone. [2]
Features

Protocol(Only for Reference)

Kinase Assay: [1]

SIRT1 fluorescence polarization assay In the SIRT1 FP assay, SIRT1 activity is monitored using a 20 amino acid peptide (Ac-Glu-Glu-Lys(biotin)-Gly-Gln-Ser-Thr-Ser-Ser-His-Ser-Lys(Ac)-Nle-Ser-Thr-Glu-Gly–Lys(MR121 or Tamra)-Glu-Glu-NH2) derived from the sequence of p53. The peptide is N-terminally linked to biotin and C-terminally modified with a fluorescent tag. The reaction for monitoring enzyme activity is a coupled enzyme assay where the first reaction is the deacetylation reaction catalyzed by SIRT1 and the second reaction is cleavage by trypsin at the newly exposed lysine residue. The reaction is stopped and streptavidin is added in order to accentuate the mass differences between substrate and product. The sensitivity of the FP assay allows identification of SRT1720. The fluorescence polarization reaction conditions are as follows: 0.5 μM peptide substrate, 150 μM βNAD+, 0-10 nM SIRT1, 25 mM Tris-acetate pH 8, 137 mM Na-Ac, 2.7 mM K-Ac, 1 mM Mg-Ac, 0.05% Tween-20, 0.1% Pluronic F127, 10 mM CaCl 2, 5 mM DTT, 0.025% BSA, and 0.15 mM nicotinamide. The reaction is incubated at 37 °C and stopped by addition of nicotinamide, and trypsin is added to cleave the deacetylated substrate. This reaction is incubated at 37 °C in the presence of 1 μM streptavidin. Fluorescent polarization is determined at excitation (650 nm) and emission (680 nm) wavelengths.

Cell Assay: [2]

Cell lines Human vascular endothelial cells (HUVECs)
Concentrations 5 μM
Incubation Time 2 hours
Method Transwell Insert Assays are utilized to measure migration. In vitro angiogenesis is assessed by Matrigel capillary-like tube structure formation assay. For endothelial tube formation assay, human vascular endothelial cells (HUVECs) are obtained from Clonetics and maintained in endothelial cell growth medium-2 containing 5% FBS. After three passages, HUVEC cell viability is measured with the trypan blue exclusion assay, and <5% of cell death is observed with SRT1720 treatment.

Animal Study: [1]

Animal Models Chase-SCID mice with MM.1S cells
Formulation 20% PEG400/0.5% Tween80/79.5% deionized water
Dosages 200 mg/kg
Administration Orally

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Milne JC, et al. Nature. 2007, 450(7170), 712-716.

[2] Chauhan D, et al. Br J Haematol. 2011, 155(5), 588-598.

Chemical Information

Download SRT1720 SDF
Molecular Weight (MW) 506.02
Formula

C25H23N7OS.HCl

CAS No. 1001645-58-4
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 38 mg/mL (75.09 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name N-(2-(3-(piperazin-1-ylmethyl)imidazo[2,1-b]thiazol-6-yl)phenyl)quinoxaline-2-carboxamide hydrochloride

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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  • Nicotinamide (Vitamin B3)

    Nicotinamide (Vitamin B3), a water-soluble vitamin, is an active component of coenzymes NAD and NADP, and also act as an inhibitor of sirtuins.

  • Quercetin

    Quercetin, a natural flavonoid present in vegetables, fruit and wine, is a stimulator of recombinant SIRT1 and also a PI3K inhibitor with IC50 of 2.4-5.4 μM. Phase 4.

  • Fisetin

    Fisetin (Fustel) is a potent sirtuin activating compound (STAC) and an agent that modulates sirtuins.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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