5.00487

Glucokinase Activator II

• Synonym(s): Glucokinase Activator II, 4-((6-(azetidine-1-carbonyl)-5-fluoropyridin-3-yl)oxy)-2-ethyl-N-(5-methylpyrazin-2-yl)-2H-indazole-6-carboxamide, Hexokinase IV Activator II, Hexokinase D Activator II, GK Activator II
• Empirical Formula (Hill Notation): C₂₄H₂₂FN₇O₃
• CAS Number: 1245214-64-5
• Molecular Weight: 475.47
• UNSPSC Code: 12352202
• NACRES: NA.77

Properties

• assay: ≥98% (HPLC)
• Quality Level: 100
• form: solid
• potency: 12 nM EC₅₀
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: off-white
• solubility: DMSO: 100 mg/mL
• storage temp.: 2-8°C

Description

General description

A cell-permeable compound that reduces glucokinase Km for glucose (EC₅₀ = 120 nM & 350 nM, for human and rat enzyme). Enhances insulin secretion from INS-1 cells upon glucose exposure.

A cell-permeable indazole derivative that reduces glucokinase K_m for glucose (EC₅₀ = 120 nM and 350 nM, respectively, for human and rat enzyme) and effectively enhances insulin secretion from rat insulinima INS-1 cells upon 5 mM glucose exposure (EC₅₀ = 170 nM). Shown to be orally available in rats (F = 69%; C_max = 1490 ng/mL; t_1/2 = 2.6 hr; AUC = 5440 ng·hr/mL; 5 mg/kg p.o.) and exhibit blood glucose lowering efficacy in OGTT (2 g/kg oral glucose challenge 1 h after single drug oral dosage) test on fasted rats (22% reduction of AUC; 250 mg/kg p.o.) in vivo.

A cell-permeable indazole derivative that reduces glucokinase K_m for glucose (EC₅₀ = 120 nM and 350 nM, respectively, for human and rat enzyme) and effectively enhances insulin secretion from rat insulinima INS-1 cells upon 5 mM glucose exposure (EC₅₀ = 170 nM). Shown to exhibit blood glucose lowering efficacy in OGTT (2 g/kg oral glucose challenge 1 h after single drug oral dosage) test among fasted rats (22% reduction of AUC; 250 mg/kg p.o.) in vivo.

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
Glucokinase

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (=2-°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Pfefferkorn, J. A., et al. 2012. Bioorg. Med. Chem. Lett.22, 7100.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable