GNE-617 hydrochloride - ≥99% , CAS No.2070014-99-0

CAS: 2070014-99-0 Cat. No.: G647284 Molecular Weight: 463.88 PubChem CID: 78357806

GRADE & PURITY ≥99%

Storage

Store at 2-8°C,Desiccated

Shipped In

Wet ice

Overview

GNE-617 hydrochloride is a specific NAMPT inhibitor that inhibits the biochemical activity of NAMPT with an IC 50 of 5 nM and exhibits efficacy in xenograft models of cancer .

In Vitro

The activity ofGNE-617 hydrochloride is evaluated on a panel 53 non-small cell lung cancer (NSCLC) cell lines in the presence or absence of 10 μM nicotinic acid. GNE-617 inhibits NAMPT IC50 of 18.9 nM in A549 cell.The majority of cell lines exhibit a steep dose response to GNE-617 when evaluated by decrease in ATP or total nucleic acid, and the cytotoxicity is completely rescued by simultaneous addition of nicotinic acid. The majority of the cell lines tested have IC 50 values below 100 nM, with approximately half with IC 50 values less than 10 nM. Eighteen cell lines are not rescued with nicotinic acid, and these non-rescuable cell lines tended to have lower IC 50 values (P=0.008, Fisher exact test, IC 50 <10 nM vs. ≥10 nM). MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

In rats, GNE-617 hydrochloride (administered QD) and GNE-875 (administered BID) are associated with more severe retinal toxicity at similar exposures and dosing duration compared with GMX-1778 (administered BID). The mouse efficacy studies using GNE-617, GNE-618, and GMX-1778 are designed to assess efficacy and opportunistically used to assess retinal toxicity in mice. NAMPTi retinal toxicity is observed with GNE-617 and GMX-1778; however, the different study durations between GNE-617 and GMX-1778 do not allow for direct comparison of retinal toxicity. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal administration

Rats Male naïve Sprague Dawley rats are administered once daily (QD) via oral gavage either (1) GNE-617 at 30 mg/kg for 2 consecutive days in combination with NA at 75 mg/kg twice daily (BID; 6 h apart); (2) GNE-618 at 30 mg/kg for 1 day; or (3) GMX-1778 at 30 mg/kg for 1 day. Dose selection for each compound is based on tolerability and toxicity findings from the safety studies and for nicotinic acid (NA) on the highest concentration of NA that could be administered to rats in a solution form. Formulating NA at higher concentration resulted in a suspension, and NA is determined to be unstable in a suspension form. GNE-617, GNE-618, and GMX-1778 are formulated as a solution in the vehicle of 60% polyethylene glycol (PEG 400)/10% ethanol/30% 5% dextrose in water (D5W) (vol/vol/vol), and NA is formulated as a solution in water. At 1 h and 6.5 h post-dose (on Day 2 for GNE-617), rats (3-4 rats per time point) are euthanized, and the blood, retina, and brain are collected. Blood samples are collected into K 2 EDTA Microtainer tubes. The tubes are chilled on wet ice until centrifugation within 30 min of collection. Plasma is collected and transferred to 1.2 mL cluster tubes. Tissues are rinsed with phosphate-buffered saline and blotted dry using gauze. All samples are stored at more than −80°C until compound analysis. Results are expressed as an absolute concentration in retina, brain, or plasma and as a ratio of retina:plasma concentration. aladdin has not independently confirmed the accuracy of these methods. They are for reference only.

Form:Solid

IC50& Target:IC50: 5 nM (NAMPT)

Specifications

Specifications & Purity

≥99%

Biochemical and Physiological Mechanisms

GNE-617 hydrochloride is a specific NAMPT inhibitor that inhibits the biochemical activity of NAMPT with an IC 50 of 5 nM and exhibits efficacy in xenograft models of cancer .

Storage

Store at 2-8°C, Desiccated

Shipped In

Wet ice

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Purity

≥99%

Names and Identifiers

• Canonical Smiles: C1=CC(=CC=C1CNC(=O)C2=CN3C=CN=C3C=C2)S(=O)(=O)C4=CC(=CC(=C4)F)F.Cl
• IUPAC Name: N-[[4-(3,5-difluorophenyl)sulfonylphenyl]methyl]imidazo[1,2-a]pyridine-6-carboxamide;hydrochloride
• InChIKey: ZTSTYFYGGLTNMN-UHFFFAOYSA-N
• INCHI: 1S/C21H15F2N3O3S.ClH/c22-16-9-17(23)11-19(10-16)30(28,29)18-4-1-14(2-5-18)12-25-21(27)15-3-6-20-24-7-8-26(20)13-15;/h1-11,13H,12H2,(H,25,27);1H
• Isomeric SMILES: C1=CC(=CC=C1CNC(=O)C2=CN3C=CN=C3C=C2)S(=O)(=O)C4=CC(=CC(=C4)F)F.Cl
• PubChem CID: 78357806
• Molecular Weight: 463.88

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Imidazopyridines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Imidazopyridines
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Imidazopyridines
• Alternative Parents: Benzenesulfonyl compounds Pyridinecarboxamides Imidazo[1,2-a]pyridines Fluorobenzenes Aryl fluorides N-substituted imidazoles Vinylogous amides Sulfones Heteroaromatic compounds Secondary carboxylic acid amides Azacyclic compounds Organooxygen compounds Hydrochlorides Hydrocarbon derivatives Organonitrogen compounds Organic oxides Organofluorides
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Imidazopyridine - Pyridinecarboxamide - Imidazo[1,2-a]pyridine - Pyridine carboxylic acid or derivatives - Benzenesulfonyl group - Fluorobenzene - Halobenzene - Aryl halide - Benzenoid - Pyridine - Monocyclic benzene moiety - Aryl fluoride - N-substituted imidazole - Heteroaromatic compound - Vinylogous amide - Sulfonyl - Sulfone - Azole - Imidazole - Secondary carboxylic acid amide - Carboxamide group - Azacycle - Carboxylic acid derivative - Organic nitrogen compound - Organonitrogen compound - Organooxygen compound - Hydrocarbon derivative - Organosulfur compound - Organic oxygen compound - Organic oxide - Hydrochloride - Organofluoride - Organohalogen compound - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as imidazopyridines. These are organic polycyclic compounds containing an imidazole ring fused to a pyridine ring. Imidazole is 5-membered ring consisting of three carbon atoms, and two nitrogen centers at the 1- and 3-positions. Pyridine is a 6-membered ring consisting of five carbon atoms and one nitrogen center.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Chemical and Physical Properties

• Solubility: DMSO : 5.56 mg/mL (11.99 mM; ultrasonic and warming and heat to 60°C)