GMX1778 (CHS828)NAMPT inhibitor CAS# 200484-11-3 |
Quality Control & MSDS
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| Cas No. | 200484-11-3 | SDF | Download SDF |
| PubChem ID | 148198 | Appearance | Powder |
| Formula | C19H22ClN5O | M.Wt | 371.86 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 39 mg/mL (104.88 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 2-[6-(4-chlorophenoxy)hexyl]-1-cyano-3-pyridin-4-ylguanidine | ||
| SMILES | C1=CC(=CC=C1OCCCCCCN=C(NC#N)NC2=CC=NC=C2)Cl | ||
| Standard InChIKey | BOIPLTNGIAPDBY-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C19H22ClN5O/c20-16-5-7-18(8-6-16)26-14-4-2-1-3-11-23-19(24-15-21)25-17-9-12-22-13-10-17/h5-10,12-13H,1-4,11,14H2,(H2,22,23,24,25) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | GMX1778(CHS-828) is a potent inhibitor of NAD+ biosynthesis enzyme NAMPT with IC50 <25 nM.
IC50 value: < 25 nM [1]
Target: NAMPT inhibitor
in 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]. References: | |||||
GMX1778 (CHS828) Dilution Calculator
GMX1778 (CHS828) Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.6892 mL | 13.4459 mL | 26.8918 mL | 53.7837 mL | 67.2296 mL |
| 5 mM | 0.5378 mL | 2.6892 mL | 5.3784 mL | 10.7567 mL | 13.4459 mL |
| 10 mM | 0.2689 mL | 1.3446 mL | 2.6892 mL | 5.3784 mL | 6.723 mL |
| 50 mM | 0.0538 mL | 0.2689 mL | 0.5378 mL | 1.0757 mL | 1.3446 mL |
| 100 mM | 0.0269 mL | 0.1345 mL | 0.2689 mL | 0.5378 mL | 0.6723 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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GMX1778 (CHS828) is a potent and specific inhibitor of nicotinamide phosphoribosyltransferase (NAMPT) with a Kd value of 120 nM [1].
NAMPT is an NAD+ biosynthesis enzyme. NAD+ is a cofactor of enzymatic redox reactions that are involved in cellular metabolism, including ATP production. NAD+ is also important in many cellular pathways responsible for gene regulation, calcium homeostasis, genomic integrity, longevity and apoptosis. Cancer cells are significantly dependent on NAD+ for supporting high levels of ATP production for rapid cell proliferation [1].
Treatment with 30 nM GMX1778 for 6 h, extracts of IM-9 cells showed decreased NAD+ and NM levels, compared to cytosolic extracts of untreated cells. These levels continued to decrease throughout the rest of the time course experiment. The most profoundly changed was the metabolite NAD+ level. Between the 6- and 20-h time points, the decline of NAD+ occurred [1].
The NAD+ salvage pathway produces NAD+ using either nicotinic acid (niacin) (NA) or nicotinamide (niacinamide) (NM) as a substrate. NAPRT1 is short for NA phosphoribosyltransferase 1. On xenograft tumors derived from NAPRT1-proficient (HCT-116) and NAPRT1-deficient (HT1080) cell lines in mice, a 24-h iv infusion of GMX1777 at 150 mg/kg or 650 mg/kg produced antitumor activity. A 4-h iv infusion of NA at 120 mg/kg did not adversely affect the antitumor activity of GMX1777 in the NAPRT1-deficient xenograft, but abolished the antitumor activity of GMX1777 against the NAPRT1-proficient HCT-116 cell line [1].
Reference:
[1]. Watson M, Roulston A, Bélec L, et al. The small molecule GMX1778 is a potent inhibitor of NAD+ biosynthesis: strategy for enhanced therapy in nicotinic acid phosphoribosyltransferase 1-deficient tumors. Molecular and cellular biology, 2009, 29(21): 5872-5888.
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