SRT1720 HCl

製品コードS1129 バッチS112908

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H23N7OS.HCl
分子量 506.02 CAS No. 1001645-58-4
Solubility (25°C)* 体外 DMSO 100 mg/mL (197.62 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
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 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 5.000mg/ml (9.88mM) Taking the 1 mL working solution as an example, add 50 μL of 100 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. 
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 SRT1720 HCl 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. SRT1720 induces autophagy.
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. [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]
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. 

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 Human vascular endothelial cells (HUVECs)
濃度 5 μM
反応時間 2 hours
実験の流れ

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.
動物実験 動物モデル Chase-SCID mice with MM.1S cells
投薬量 200 mg/kg
投与方法 Orally

参考

  • https://pubmed.ncbi.nlm.nih.gov/18046409/
  • https://pubmed.ncbi.nlm.nih.gov/21950728/

カスタマーフィードバック

Data from [Data independently produced by Aging Cell, 2014, 13(5), 890-9]

Data from [Data independently produced by J Neurosci, 2014, 34(36), 11897-912]

Data from [Data independently produced by J Biol Chem, 2014, 289(29), 20012-25]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Zinc Alleviates Diabetic Muscle Atrophy via Modulation of the SIRT1/FoxO1 Autophagy Pathway Through GPR39 [ J Cachexia Sarcopenia Muscle, 2025, 16(2):e13771] PubMed: 40026072
SIRT1 and its SUMOylation attenuate hyperoxia-induced lung injury by improving mitochondrial biogenesis and fusion [ Free Radic Biol Med, 2025, 236:98-115] PubMed: 40403939
A novel SIRT1 activator attenuates neuropathic pain by inhibiting spinal neuronal activation via the SIRT1-mGluR1/5 pathway [ Cell Biol Toxicol, 2025, 41(1):24] PubMed: 39779529
The Sirt1 Activator SRT1720 Mitigates Human Monocyte Activation and Improves Outcome During Gram-Negative Pneumosepsis in Mice [ Int J Mol Sci, 2025, 26(19)9309] PubMed: 41096578
A Decoy Oligodeoxynucleotides Disturbing Forkhead Box O3 Mediated ctnna2 Transcriptional Repression Prevents Postoperative Neurocognitive Disorder in Mice [ CNS Neurosci Ther, 2025, 31(8):e70454] PubMed: 40859434
Liu Wei Di Huang Decoction Alleviates Renal Fibrosis by Inhibiting Endothelial Mesenchymal Transitions via Upregulating Sirt1 Expression and Inhibiting the Wnt/β-Catenin Signaling Pathway [ Drug Des Devel Ther, 2025, 19:6587-6603] PubMed: 40761667
Inhibition SIRT1 to regulate FOXP3 or RORγt can restore the balance of Treg/Th17 axis in ulcerative colitis and enhance the anti-inflammatory effect of moxibustion [ Front Immunol, 2024, 15:1525469] PubMed: 39867884
TNF-α-downregulated SIRT1 regulates mitochondrial-autophagy and apoptosis in renal vascular endothelial cells involved in trichloroethylene-induced immune kidney injury [ Int Immunopharmacol, 2024, 143(Pt 2):113521] PubMed: 39476564
SIRT1 Regulates Mitochondrial Damage in N2a Cells Treated with the Prion Protein Fragment 106-126 via PGC-1α-TFAM-Mediated Mitochondrial Biogenesis [ Int J Mol Sci, 2024, 25(17)9707] PubMed: 39273653
Protectin D1 ameliorates non-compressive lumbar disc herniation through SIRT1-mediated CGRP signaling [ Mol Pain, 2024, 20:17448069241232349] PubMed: 38288478

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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