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5mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Purity: ≥98%
GMX1778 (GMX 1778; CHS828; GMX-1778; CHS-828) is a potent and selective/specific inhibitor of nicotinamide phosphoribosyltransferase (NAMPT) with potential antitumor activity. It inhibits NAMPT with an IC50 and Kd of < 25 nM and 120 nM, respectively. GMX-1778 demonstrates significant in vivo antitumor efficacy in nude mice bearing midgut carcinoid (GOT1), pancreatic carcinoid (BON) and medullary thyroid cancer (GOT2) tumors.
ln Vitro |
CHS-828 (GMX1778) showed a phosphoribosyltransferase activity inhibition threshold of less than 25 nM for recombinant NAMPT, but not for recombinant NMNAT1's adenyltransferase activity. Using a fluorescent tag (CHS-828 (GMX1778)-Alexa Fluor), the recombinant NAMPT for GMX1778 had a Kd of 120 nM. In response to a 3 nM GMX1778 challenge, overexpression of wild-type NAMPT was able to sustain a certain level of NAD+; however, this effect was eliminated when cells were subjected to 300 nM CHS-828 (GMX1778). Through a rise in superoxide and a decrease in intracellular NAD(+), CHS-828 (GMX1778) raises intracellular ROS in cancer cells. Interestingly, ROS are not produced in normal cells by CHS-828 (GMX1778) treatment. In a way that is dependent on NA phosphoribosyltransferase 1 (NAPRT1), nicotinic acid (NA) can reduce ROS produced by CHS-828 (GMX1778)[2].
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ln Vivo |
In the NAPRT1-deficient xenograft trials, a 24-hour intravenous infusion of CHS-828 (GMX1778) at a dose of 150 mg/kg or 650 mg/kg did not negatively impact the antitumor efficacy of a 4-hour intravenous infusion of NA (120 mg/kg of body weight). At 650 mg/kg, CHS-828 (GMX1778) exceeds the highest dosage that can be tolerated. Following treatment with 750 mg/kg CHS-828 (GMX1778), the administration of NA as a 4-hour intravenous infusion decreased the mortality linked to hazardous levels of GMX1777[2].
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Animal Protocol |
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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 |
Molecular Formula |
C19H22CLN5O
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Molecular Weight |
371.86
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CAS # |
200484-11-3
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SMILES |
N#C/N=C(NC1=CC=NC=C1)\NCCCCCCOC2=CC=C(Cl)C=C2
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Synonyms |
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.6892 mL | 13.4459 mL | 26.8918 mL | |
5 mM | 0.5378 mL | 2.6892 mL | 5.3784 mL | |
10 mM | 0.2689 mL | 1.3446 mL | 2.6892 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.