Introduction：Basic information about CAS 200484-11-3|GMX1778, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
GMX1778(CHS-828) is a potent inhibitor of NAD+ biosynthesis enzyme NAMPT with IC50 <25 nM.IC50 value: < 25 nM [1]Target: NAMPT inhibitorin vitro: The phosphoribosyltransferase activity of recombinant NAMPT was sensitive to inhibition by 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 (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 GMX1778 [1]. GMX1778 increases intracellular ROS in cancer cells by elevating the superoxide level while decreasing the intracellular NAD(+) level. Notably, GMX1778 treatment does not induce ROS in normal cells. 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 GMX1777 at a dose of 150 mg/kg or 650 mg/kg in the NAPRT1-deficient xenograft experiments. GMX1777 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 GMX1777 reduced the mortality associated with toxic doses of GMX1777 [1].
Related Catalog
Signaling Pathways >>Metabolic Enzyme/Protease >>NamptResearch Areas >>Cancer
References
[1]. Watson M, et al. The small molecule GMX1778 is a potent inhibitor of NAD+ biosynthesis: strategy for enhanced therapy in nicotinic acid phosphoribosyltransferase 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 reactive oxygen species (ROS)-mediated cytotoxicity in a p53- and nicotinic acid phosphoribosyltransferase1 (NAPRT1)-dependent manner. J Biol Chem. 2012 Jun 22;287(26):22408-17.
Chemical & Physical Properties
Density
1.2±0.1 g/cm3
Boiling Point
526.9±58.0 °C at 760 mmHg
Molecular Formula
C19H22ClN5O
Molecular Weight
371.864
Flash Point
272.4±32.3 °C
Exact Mass
371.151276
PSA
82.33000
LogP
4.95
Appearance of Characters
white solid
Vapour Pressure
0.0±1.4 mmHg at 25°C
Index of Refraction
1.587
InChIKey
BOIPLTNGIAPDBY-UHFFFAOYSA-N
SMILES
N#CNC(=NCCCCCCOc1ccc(Cl)cc1)Nc1ccncc1
Storage condition
-20℃
Safety Information
Symbol
GHS07
Signal Word
Warning
Hazard Statements
H302-H315-H319-H335
Precautionary Statements
P301 + P312 + P330-P305 + P351 + P338
RIDADR
NONH for all modes of transport
Articles1
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Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD(+) biosynthesis from nicotinamide, is one of the major factors regulating cancer cells metabolism and is considered a pr...
