SAR405 - Vps34 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESAR405Cat. No.: HY-12481CAS No.: 1523406-39-4分式: CHClFNO分量: 443.85作靶點(diǎn): PI3K; Autophagy作通路: PI3K/Akt/mTOR; Autophagy儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 27 mg/mL (60.83 mM)* means

2、 soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.2530 mL 11.2651 mL 22.5301 mL5 mM 0.4506 mL 2.2530 mL 4.5060 mL10 mM 0.2253 mL 1.1265 mL 2.2530 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前?qǐng)先配制澄清的儲(chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您

3、現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.63 mM); Clear solution2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.63 mM); Clear solution3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master

4、of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (5.63 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 SAR405PIK3C3/Vps34 的抑制劑，IC50為1.2 nM。SAR405可防噬并與腫瘤細(xì)胞中的MTOR抑制作協(xié)同。IC50 & Target Vps34 Autophagy1.2 nM (IC50)體外研究 SAR405 is a low-molecular-mass kinase inhibitor of Vps34 (KD 1.5 nM). SAR405 has a

5、n exquisite proteinand lipid kinase selectivity profile that is explained by its unique binding mode and molecular interactionswithin the ATP binding cleft of human Vps34. Inhibition of Vps34 kinase activity by SAR405 affects both lateendosome-lysosome compartments and prevents autophagy. SAR405 sho

6、ws a binding equilibrium constantKD of 1.520.77 nM (s.d.) and a dissociation rate constant, koff, of 3.03 0.55 10-3 s-1, corresponding to aresidence half-life, t1/2, of 3.8 min. The activity of SAR405 is next evaluated on a dedicated Vps34 cellularassay using a GFP-FYVEtransfected HeLa cell line 1.

7、SAR405 is a PIK3C3/Vps34 inhibitor that preventsautophagy and synergizes with MTOR inhibition in tumor cells. SAR405 is a proximal inhibitor of theautophagy machinery. SAR405 prevents autophagosome formation with an IC50 of 42 nM. Treatment ofstarved cells with SAR405 completely inhibits the convers

8、ion to LC3-II in a dose-dependent manner. Theeffect of SAR405 on autophagy is then investigated. The GFP-LC3 model is used for the HTS and confirmedits activity on starved cells (IC50=419 nM). The conversion of LC3-I into LC3-II is also analyzed by westernblotting on wild-type HeLa and H1299 cells 2

9、.PROTOCOLKinase Assay 1 KiNativ profiling is performed. Jurkat cell lysates are treated with 1 M of SAR405. After 15-min incubation,the desthiobiotin-ATP-acylphosphate probe is added and incubated for 10 min. Samples are prepared fortargeted MS analysis. Briefly, samples are prepared for trypsin dig

10、estion (denature and then reduce alkylate)and digested with trypsin, and desthiobiotinylated peptides are enriched on streptavidin resin. Enrichedprobe-labeled peptides are analyzed by LC tandem MS on a Thermo-LTQ ion trap mass spectrometer usingproprietary data collection methodology. All quantific

11、ation is performed by extracting characteristic fragmention signals from targeted MS/MS spectra and comparing signals in control and treated samples 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Nat Commun. 2018 Jan 18;9(1):291. Biochim

12、Biophys Acta Mol Cell Res. 2019 May;1866(5):793-805.See more customer validations on HYPERLINK / www.MedChemE2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEREFERENCES1. Ronan B, et al. A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat Chem Biol. 2014Dec;10(12):1013-9.2. Pasquier B. SAR405, a PIK3C3/Vps34 inhibitor that prevents autophagy and synergizes with MTOR inhibition in tumor cells. Autophagy.2015 Apr 3;11(4):725-6.McePdfHeightC