E-Daporinad-FK866-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemE(E)-DaporinadCat. No.: HY-50876CAS No.: 658084-64-1Synonyms: FK866; APO866分式: CHNO分量: 391.51作靶點(diǎn): Nampt; Autophagy作通路: Metabolic Enzyme/Protease; Autophagy儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)

2、據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (127.71 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.5542 mL 12.7711 mL 25.5421 mL5 mM 0.5108 mL 2.5542 mL 5.1084 mL10 mM 0.2554 mL 1.2771 mL 2.5542 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥式選擇適當(dāng)?shù)娜芙獍福渲魄罢埾扰?/p>

3、制澄清的儲備液，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，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，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. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.39 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.39 mM); Clear solution1/3 Ma

4、ster of Small Molecules 您邊的抑制劑師www.MedChemE3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.39 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 (E)-Daporinad (FK866)是煙酰胺磷酸核糖轉(zhuǎn)移酶 (NMPRTase) 的有效抑制劑， IC50 為 0.09 nM。IC50 & Target IC50: 0.09 nM (NMPRTase)體外研究 Nampt inhibition with (E)-Daporinad (FK866

5、) induces significant NAD+ intracellular reduction and selectivelykills MM cells. (E)-Daporinad (FK866)-induced cell death is associated with inhibition of Nampt activity, ratherthan protein expression, and higher NAD+ baseline levels in MM cells than normal PBMCs confer (E)-Daporinad (FK866) sensit

6、ivity. (E)-Daporinad (FK866) abrogates the survival advantage conferred by thebone marrow microenvironment 1. (E)-Daporinad (FK866) prevents the Ca2+i increase induced bydifferent mitogens and reduces the Ca2+ content of TG-responsive Ca2+ stores in Jurkat and in activatedPBLs. (E)-Daporinad (FK866)

7、 reduces the Ca2+ content of TG-responsive Ca2+ stores in Jurkat cells but notin Bcl2-Jurkat cells 2. Inhibition of NAMPT by (E)-Daporinad (FK866), or inhibition of SIRT by nicotinamidedecreases proliferation and triggered death of 293T cells involving the p53 acetylation pathway 3.體內(nèi)研究 (E)-Daporina

8、d (FK866) (30 mg/kg, i.p.) decreases the tumor burden in CB17-SCID mice, and the tumortissue demonstrates a significant decrease in ERK phosphorylation and proteolytic cleavage of LC3 1.PROTOCOLCell Assay 1 MM1S cells (2104 cells/well) are cultured for 72 and 96 hours in BMSC-coated 96-well plates i

9、n thepresence or absence of drug. DNA synthesis is measured by (3H)-thymidine uptake, with (3H)-thymidineadded (0.5 Ci/well) during the last 8 hours of cultures.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal CB17-SCID mice (28-35 days old) are i

10、rradiated (200 cGy), and then inoculated subcutaneously in the rightAdministration 1 flank with 3106 MM1S cells in 100 L RPMI 1640. After detection of tumor (2 weeks after the injection), 7mice are treated intraperitoneally with either vehicle or (E)-Daporinad (FK866) (30 mg/kg body weight) twicea d

11、ay for 4 days, repeated weekly over 3 weeks. Caliper measurements of the longest perpendicular tumordiameters are performed twice a week to estimate the tumor volume using the following formula:lengthwidth20.5. Tumor growth inhibition (TGI) is calculated. Animals are killed when tumors reach 2cm3 or

12、 the mice appear moribund. Survival is evaluated from the first day of treatment until death.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) Mol Med Rep. 2017 Oct;16(4):5121-5128. Patent. US20180263995A1.2/3 Master of Small Molecules 您邊的抑制劑師

13、www.MedChemESee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Cea M, et al. Targeting NAD+ salvage pathway induces autophagy in multiple myeloma cells via mTORC1 and extracellular signal-regulated kinase (ERK1/2) inhibition. Blood. 2012 Oct 25;120(17):3519-29.2. Magnone M, et al.

14、 NAD+ levels control Ca2+ store replenishment and mitogen-induced increase of cytosolic Ca2+ by Cyclic ADP-ribose-dependent TRPM2 channel gating in human T lymphocytes. J Biol Chem. 2012 Jun 15;287(25):21067-81.3. Thakur BK, et al. Inhibition of NAMPT pathway by FK866 activates the function of p53 in HEK293T cells. Biochem Biophys ResCommun. 2012 Aug 3;4