CHS-828 (GMX1778) is a competitive inhibitor ofnicotinamide phosphoribosyltransferase (NAMPT), with anIC₅₀less 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:< 25 nM (NAMPT)^[1].

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].

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].

371.86

Solid

C₁₉H₂₂ClN₅O

200484-11-3

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 39 mg/mL(104.88 mM)

*"≥" means soluble, but saturation unknown.

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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (6.72 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.72 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。