1、Product Data Sheet(E)-DaporinadCat. No.: HY-50876CAS No.: 658084-64-1分式: CHNO分量: 391.51作靶點: 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溶解性數據體外實驗 DMSO : 50 mg/mL (127.71 mM)H2O : 0.1 mg/mL (insoluble)* means soluble,

2、but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration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請根據產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內使，-20C 儲存時，請在 1 個

3、內使。體內實驗請根據您的實驗動物和給藥式選擇適當的溶解案。以下溶解案都請先按照 In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結果的可靠性，澄 的儲備液可以根據儲存條件，適當保存；體內實驗的作液，建議您現現配，當天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現沉淀、析出現象，可以通過加熱和/或超聲的式助溶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 solution此案可獲得 2.5 mg/mL (6

4、.39 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續加 450 L 理鹽定容 1 mL。2. 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 solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (6.39 mM，飽和度未知) 的澄清溶液。以 1 mL 作液

5、為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.39 mM); Clear solution此案可獲得 2.5 mg/mL (6.39 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 (E)-Daporinad

6、 (FK866)是煙酰胺磷酸核糖轉移酶 (NMPRTase; Nampt) 的有效抑制劑， IC50 為 0.09 nM。IC & Target IC50: 0.09 nM (NMPRTase)體外研究 Nampt inhibition with (E)-Daporinad (FK866) induces significant NAD+ intracellular reduction and selectively kills MMcells. (E)-Daporinad (FK866)-induced cell death is associated with inhibition of

7、Nampt activity, rather than proteinexpression, and higher NAD+ baseline levels in MM cells than normal PBMCs confer (E)-Daporinad (FK866) sensitivity.(E)-Daporinad (FK866) abrogates the survival advantage conferred by the bone marrow microenvironment1. (E)-Daporinad (FK866) prevents the Ca2+i increa

8、se induced by different mitogens and reduces the Ca2+ content of TG-responsive Ca2+ stores in Jurkat and in activated PBLs. (E)-Daporinad (FK866) reduces the Ca2+ content of TG-responsive Ca2+ stores in Jurkat cells but not in Bcl2-Jurkat cells2. Inhibition of NAMPT by (E)-Daporinad (FK866), orinhib

9、ition of SIRT by nicotinamide decreases proliferation and triggered death of 293T cells involving the p53acetylation pathway3.體內研究 (E)-Daporinad (FK866) (30 mg/kg, i.p.) decreases the tumor burden in CB17-SCID mice, and the tumor tissuedemonstrates a significant decrease in ERK phosphorylation and p

10、roteolytic cleavage of LC31.PROTOCOLCell Assay 1 MM1S cells (2104 cells/well) are cultured for 72 and 96 hours in BMSC-coated 96-well plates in the presence orabsence of drug. DNA synthesis is measured by (3H)-thymidine uptake, with (3H)-thymidine added (0.5 Ci/well)during the last 8 hours of cultur

11、es.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal CB17-SCID mice (28-35 days old) are irradiated (200 cGy), and then inoculated subcutaneously in the right flank withAdministration 1 3106 MM1S cells in 100 L RPMI 1640. After detection of tumor (

12、2 weeks after the injection), 7 mice are treatedintraperitoneally with either vehicle or (E)-Daporinad (FK866) (30 mg/kg body weight) twice a day for 4 days,repeated weekly over 3 weeks. Caliper measurements of the longest perpendicular tumor diameters are performedtwice a week to estimate the tumor

13、 volume using the following formula: lengthwidth20.5. Tumor growth inhibition(TGI) is calculated. Animals are killed when tumors reach 2 cm3 or the mice appear moribund. Survival is evaluatedfrom the first day of treatment until death.MCE has not independently confirmed the accuracy of these methods

14、. They are for reference only.戶使本產品發表的科研獻Page 2 of 3 www.MedChemE Mol Med Rep. 2017 Oct;16(4):5121-5128. bioRxiv. 2019 Oct. Patent. US20180263995A1.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Cea M, et al. Targeting NAD+ salvage pathway induces autophagy in multi

15、ple 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. NAD+ levels control Ca2+ store replenishment and mitogen-induced increase of cytosolic Ca2+ by Cyclic ADP-ribose-dependentTRPM2 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 Res Commun. 2012 Aug3