product name GMX1778 (CHS828)
Description: GMX1778 (also known as CHS828) is a potent and specific inhibitor of nicotinamide phosphoribosyltransferase (NAMPT) with IC50 and Kd of < 25 nM and 120 nM, respectively. GMX-1778 inhibits cellular synthesis of NAD. CHS 828 kill tumour cells by inhibiting the nuclear factor-kappaB translocation but unlikely through down-regulation of proteasome. GMX-1778 has shown promising anticancer activity in experimental tumor models and primary cultures of cancer cells from patients.
References: Mol Cell Biol. 2009 Nov;29(21):5872-88; Neuroendocrinology. 2005;82(3-4):171-6.
371.86
Formula
C19H22ClN5O
CAS No.
200484-11-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 74 mg/mL (199 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: GMX1778 induces NAD+ depletion through inhibition of NAD+ biosynthesis, followed by ATP depletion and ultimately resulted in cell death. GMX1778 induces programmed cell death with apoptotic features. GMX1778 suppresses nuclear factor-kappa B activity in cancer cells through downregulation of IKK activity (IC50=8 NM). Kinase Assay: Recombinant NAMPT activity is assessed using a coupled-enzyme assay based on the quantitation of NAD+. Reactions are performed at room temperature for 180 min using mixtures consisting of 50 mM HEPES (pH 7.4), 50 mM KCl, 5 mM MgCl2, 0.5 mM β-mercaptoethanol, 0.005% bovine serum albumin, 1% DMSO, 2.0 U/ml lactate dehydrogenase, 4 mM sodium L-lactate, 0.4 U/ml diaphorase, 6 μΜ resazurin sodium salt, 0.4 mM PRPP, 3.0 nM NMNAT1, 125 μM ATP, 50 μM NM, and 2 to 5 μM recombinant NAMPT. Fluorescence s measured with a Tecan Safire plate reader (excitation wavelength, 560 nm; emission wavelength, 590 nm). Ki values are calculated using Graphpad Prism 4.0 software and the Cheng-Prusoff equation. Cell Assay: Serial dilutions of GMX1778 in DMSO are performed to achieve a final concentration of 0.2% DMSO. Relative ATP levels after 72 h are determined using a ViaLight HS high-sensitivity cytotoxicity and cell proliferation BioAssay kit per the manufacturers instructions. For GMX1778 cytotoxicity rescue experiments, cells are treated with NA (10 μM) or NMN (100 μM) simultaneously with GMX1778. Sigmoidal dose-response curves are generated by nonlinear regression analysis of variable slope using GraphPad Prism version 4.00 (GraphPad Software) to calculate 50% inhibitory (IC50) values. |
|---|---|
| In Vivo | GMX1778 (250 mg/kg, p.o.) shows marked antitumoural activity against three different human neuroendocrine tumours, midgut carcinoid (GOT1), pancreatic carcinoid (BON), and medullary thyroid carcinoma (GOT2), transplanted in nude mice |
| Animal model | Nude mice bearing midgut carcinoid (GOT1), pancreatic carcinoid (BON) and medullary thyroid cancer (GOT2) tumors |
| Formulation & Dosage | Dissolved in 2% carboxymethyl cellulose in 0.9% saline; 250 mg/kg; oral administration |
| References | Mol Cell Biol. 2009 Nov;29(21):5872-88; Neuroendocrinology. 2005;82(3-4):171-6. |
