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GMX1778 (CHS828)

Alias: CHS828; GMX-1778;CHS 828; GMX1778; CHS-828;GMX 1778.
Cat No.:V0961 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.
GMX1778 (CHS828)
GMX1778 (CHS828) Chemical Structure CAS No.: 200484-11-3
Product category: NAMPT
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
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Other Forms of GMX1778 (CHS828):

  • CHS-828 (nicotinate)
Official Supplier of:
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Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

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.

Biological Activity I Assay Protocols (From Reference)
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].
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].
Animal Protocol
Dissolved in 2% carboxymethyl cellulose in 0.9% saline; 250 mg/kg; oral administration
Nude mice bearing midgut carcinoid (GOT1), pancreatic carcinoid (BON) and medullary thyroid cancer (GOT2) tumors
References

[1]. 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]. 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. J Biol Chem. 2012 Jun 22;287(26):22408-17.

Additional Infomation
2-[6-(4-chlorophenoxy)hexyl]-1-cyano-3-pyridin-4-ylguanidine is an aromatic ether.
CHS-828 has been used in trials studying the treatment of Unspecified Adult Solid Tumor, Protocol Specific.
Pyridyl Cyanoguanidine CHS 828 is a pyridyl cyanoguanidine that exhibits antitumor activity by an unknown mechanism. (NCI)
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C19H22CLN5O
Molecular Weight
371.86
Exact Mass
371.151
CAS #
200484-11-3
Related CAS #
1160589-73-0 (nicotinate);200484-11-3 (free);
PubChem CID
148198
Appearance
White to off-white solid powder
Density
1.2±0.1 g/cm3
Boiling Point
526.9±58.0 °C at 760 mmHg
Flash Point
272.4±32.3 °C
Vapour Pressure
0.0±1.4 mmHg at 25°C
Index of Refraction
1.587
LogP
4.95
Hydrogen Bond Donor Count
2
Hydrogen Bond Acceptor Count
4
Rotatable Bond Count
11
Heavy Atom Count
26
Complexity
450
Defined Atom Stereocenter Count
0
InChi Key
BOIPLTNGIAPDBY-UHFFFAOYSA-N
InChi Code
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)
Chemical Name
2-[6-(4-chlorophenoxy)hexyl]-1-cyano-3-pyridin-4-ylguanidine
Synonyms
CHS828; GMX-1778;CHS 828; GMX1778; CHS-828;GMX 1778.
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 74 mg/mL (199 mM)
Water:<1 mg/mL
Ethanol:<1 mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.72 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

 (Please use freshly prepared in vivo formulations for optimal results.)
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.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00457574 Withdrawn Drug: GMX1777 Solid Tumors and Lymphomas Gemin X March 2007 Phase 1
NCT00724841 Terminated Drug: Obatoclax Mesylate
Drug: Temozolomide
Metastatic Melanoma Gemin X June 2008 Phase 1
Phase 2
Biological Data
  • GMX1778 (CHS828)

    Characterization of GMX1778 cytotoxicity. (A) HeLa cells are protected from GMX1778 cytotoxicity by NA. Mol Cell Biol. 2009 Nov;29(21):5872-88.
  • GMX1778 (CHS828)

    Modulation of NAMPT expression alters the sensitivity of tumor cell lines to GMX1778. Mol Cell Biol. 2009 Nov;29(21):5872-88.
  • GMX1778 (CHS828)

    Inverse correlation of NAMPT expression with GMX1778 cytotoxicity in tumor cell lines. Mol Cell Biol. 2009 Nov;29(21):5872-88.
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