| Bioactivity | 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]. | ||||||||||||
| Invitro | 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]. | ||||||||||||
| Name | CHS-828 | ||||||||||||
| CAS | 200484-11-3 | ||||||||||||
| Formula | C19H22ClN5O | ||||||||||||
| Molar Mass | 371.86 | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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