CHS-828-GMX1778-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECHS-828Cat. No.: HY-10079CAS No.: 200484-11-3Synonyms: GMX1778分式: CHClNO分量: 371.86作靶点: Nampt作通路: Metabolic Enzyme/Protease储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 39 mg/mL (104.88 mM

2、)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.6892 mL 13.4459 mL 26.8918 mL5 mM 0.5378 mL 2.6892 mL 5.3784 mL10 mM 0.2689 mL 1.3446 mL 2.6892 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内

3、实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.72 mM); Clear solution1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 CHS-828 (GMX1778)种竞争性的烟酰胺磷酸化转移酶抑制剂 (NAMPT)，其 IC50 值 25nM。CHS-828(GMX1778) 通过降低细胞中的

4、 NAD+ 平发挥细胞毒性作，具有较强的抗癌活性 1。IC50 & Target IC50: 25 nM (NAMPT) 1.体外研究 The phosphoribosyltransferase activity of recombinant NAMPT was sensitive to inhibition by CHS-828(GMX1778) (IC50 25 nM) whereas the adenyltransferase activity of recombinant NMNAT1 was not. The Kdof recombinant NAMPT for GMX1778 la

5、beled with a fluorescent tag (CHS-828 (GMX1778)-Alexa Fluor) was120 nM. Overexpression of wild-type NAMPT was able to maintain a certain level of NAD+ under conditionsof challenge with 3 nM GMX1778, but this effect was lost when cells were exposed to 300 nM CHS-828(GMX1778) 1. CHS-828 (GMX1778) incr

6、eases intracellular ROS in cancer cells by elevating the superoxidelevel while decreasing the intracellular NAD(+) level. Notably, CHS-828 (GMX1778) treatment does notinduce ROS in normal cells. CHS-828 (GMX1778)-induced ROS can be diminished by adding nicotinic acid(NA) in a NA phosphoribosyltransf

7、erase 1 (NAPRT1)-dependent manner 2.体内研究 A 4-h iv infusion of NA (120 mg/kg of body weight) did not adversely affect the antitumor activity of a 24-h ivinfusion of CHS-828 (GMX1778) at a dose of 150 mg/kg or 650 mg/kg in the NAPRT1-deficient xenograftexperiments. CHS-828 (GMX1778) at 650 mg/kg is ab

8、ove the maximum tolerated dose. The administrationof NA as a 4-h iv infusion immediately following treatment with 750 mg/kg CHS-828 (GMX1778) reduced themortality associated with toxic doses of GMX1777 2.REFERENCES1. Watson M, et al. The small molecule GMX1778 is a potent inhibitor of NAD+ biosynthe

9、sis: strategy for enhanced therapy in nicotinic acidphosphoribosyltransferase 1-deficient tumors. Mol Cell Biol. 2009 Nov;29(21):5872-88.2. Cerna D, et al. Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) activity by small molecule GMX1778 regulates reactiveoxygen species (ROS)-mediated cytotoxicity in a p53- and nicotinic acid phosphoribosyltransferase1 (NAPRT1)-dependent manner. J BiolChem. 2012 Jun 22;287(26):22408-17.McePdfHeightCaution: Product has not been fully validated fo