SRT1720 HCl

製品コードS1129 バッチS112909

化学情報

	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
* <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. 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]
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]

プロトコル(参考用のみ)

キナーゼアッセイ	SIRT1 fluorescence polarization assay
キナーゼアッセイ	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

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：

Protectin D1 ameliorates non-compressive lumbar disc herniation through SIRT1-mediated CGRP signaling [ Mol Pain, 2024, 20:17448069241232349]	PubMed: 38288478
SIRT1 mediates the antagonism of Wnt/β-catenin pathway by vitamin D in colon carcinoma cells. [ bioRxiv, 2024, 10.1101/2024.01.21.576539]	PubMed: none
SRT1720, an activator of silent information regulator 1, alleviates acute traumatic brain injury in a rat model [ Chinese Journal of Tissue Engineering Research, 2024, (28): 4447-4454.]	PubMed: none
Vascular Electrical Stimulation with Wireless, Battery-Free, and Fully Implantable Features Reduces Atherosclerotic Plaque Formation Through Sirt1-Mediated Autophagy [ Small, 2023, e2300584.]	PubMed: 37267941
SIRT1 attenuates blood-spinal cord barrier disruption after spinal cord injury by deacetylating p66Shc [ Redox Biol, 2023, 60:102615]	PubMed: 36716673
Cooperative effects of SIRT1 and SIRT2 on APP acetylation [ Aging Cell, 2023, e13967.]	PubMed: 37602729
Sirtuin 1 alleviates alcoholic liver disease by inhibiting HMGB1 acetylation and translocation [ PeerJ, 2023, 11:e16480]	PubMed: 38034869
SRT2183 and SRT1720, but not Resveratrol, Inhibit Osteoclast Formation and Resorption in the Presence or Absence of Sirt1 [ J Bone Res, 2023, 11(4)1000235]	PubMed: 37711761
The ZIP8/SIRT1 axis regulates alveolar progenitor cell renewal in aging and idiopathic pulmonary fibrosis [ J Clin Invest, 2022, 132(11)e157338]	PubMed: 35389887
Systematic pan-cancer analysis identifies APOC1 as an immunological biomarker which regulates macrophage polarization and promotes tumor metastasis [ Pharmacol Res, 2022, 183:106376]	PubMed: 35914680

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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