SKU : MC537523
CAS Number : 200484-11-3
Molecular Formula : C19H22ClN5O | Molecular Weight : 371.86
Synonyms : GMX1778
Quote RequestPurity | NLT 98% |
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Storage | at 20ºC 2 years |
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Chemical Name | CHS-828 |
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CAS Number | 200484-11-3 |
MDL Number | MFCD03700766 |
Molecular Formula | C19H22ClN5O |
Molecular Weight | 371.86 |
Synonyms | GMX1778 |
CHS-828 (GMX1778) is a competitive inhibitor of nicotinamide phosphoribosyltransferase (NAMPT), with an IC50 less than 25 nM. CHS-828 (GMX1778) exerts a cytotoxic effect by decreasing the cellular level of NAD+ and exhibits a potent anticancer activity[1]. IC50 & Target: IC50: < 25 nM (NAMPT)[1]. In Vitro: 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 Kd of recombinant NAMPT for GMX1778 labeled with a fluorescent tag (CHS-828 (GMX1778)-Alexa Fluor) was 120 nM. Overexpression of wild-type NAMPT was able to maintain a certain level of NAD+ under conditions of challenge with 3 nM GMX1778, but this effect was lost when cells were exposed to 300 nM CHS-828 (GMX1778)[1]. CHS-828 (GMX1778) increases intracellular ROS in cancer cells by elevating the superoxide level while decreasing the intracellular NAD(+) level. Notably, CHS-828 (GMX1778) treatment does not induce ROS in normal cells. CHS-828 (GMX1778)-induced ROS can be diminished by adding nicotinic acid (NA) in a NA phosphoribosyltransferase 1 (NAPRT1)-dependent manner[2]. In Vivo: A 4-h iv infusion of NA (120 mg/kg of body weight) did not adversely affect the antitumor activity of a 24-h iv infusion of CHS-828 (GMX1778) at a dose of 150 mg/kg or 650 mg/kg in the NAPRT1-deficient xenograft experiments. CHS-828 (GMX1778) at 650 mg/kg is above the maximum tolerated dose. The administration of NA as a 4-h iv infusion immediately following treatment with 750 mg/kg CHS-828 (GMX1778) reduced the mortality associated with toxic doses of GMX1777[2].
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