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作靶點(diǎn): Nampt作通路: Metabolic Enzyme/Protease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 : 39 mg/mL (104.88 mM

2、)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液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)娜芙獍福渲魄罢?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)

3、實(shí)驗(yàn)的作液，建議您現(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 90% corn oilSolubility: 2.5 mg/mL (6.72 mM); Clear solution1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 CHS-828 (GMX1778)種競(jìng)爭(zhēng)性的煙酰胺磷酸化轉(zhuǎn)移酶抑制劑 (NAMPT)，其 IC50 值 25nM。CHS-828(GMX1778) 通過(guò)降低細(xì)胞中的

4、 NAD+ 平發(fā)揮細(xì)胞毒性作，具有較強(qiáng)的抗癌活性 1。IC50 & Target IC50: 25 nM (NAMPT) 1.體外研究 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.體內(nèi)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