5.34032

NOX Inhibitor IV, GKT136901

• Synonym(s): NOX Inhibitor IV, GKT136901, 2-(2-Chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo-[4,3-c]pyridine-3,6(2H,5H)-dione, NADPH Oxidase Inhibitor IV, Dual NOX4/NOX1 Inhibitor, GKT-136901
• Empirical Formula (Hill Notation): C₁₉H₁₅ClN₄O₂
• CAS Number: 955272-06-7
• Molecular Weight: 366.80
• MDL number: MFCD09961532
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• assay: ≥98% (HPLC)
• Quality Level: 100
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: pale yellow to brown
• solubility: DMSO: 50 mg/mL
• storage temp.: 2-8°C
• SMILES string: Clc1c(cccc1)[n]2[nH]c3c([c]2=O)c([n]([c](c3)=O)Cc4ncccc4)C
• InChI: 1S/C19H15ClN4O2/c1-12-18-15(10-17(25)23(12)11-13-6-4-5-9-21-13)22-24(19(18)26)16-8-3-2-7-14(16)20/h2-10,22H,11H2,1H3
• InChI key: DNKYHHFCPXKFIY-UHFFFAOYSA-N

Description

General description

An orally bioavailable, non-toxic pyrazolopyridinedione based compound that acts as a potent and reversible inhibitor of NOX1- and NOX4-containing NADPH oxidase activity (K_i = 160 and 165 nM, respectively, Amplex Red assay) and devoid of antioxidant properties. At higher concentrations, affects NOX2 (K_i = 1.53 uM). Blocks NOX-mediated ROS (reactive oxygen species) outburst in NOX isozyme expressing PMN cell membranes. Exhibits poor affinity towards xanthine oxidase, lipoxygenases-5/12, myeloperoxidase, MAO-B, iNOS and eNOS, several cytochrome P450 isozymes, PTP1B and a panel containing representative ion-channels and kinases at 10 µM. Functions as a selective scavenger of peroxynitrite over nitric oxide, superoxide radical anion and hydroxyl radical.

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
NOX1- and NOX4-containing NADPH oxidase activity

Reversible: yes

Packaging

Packaged under inert gas

Preparation Note

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

Use only fresh DMSO for reconstitution.

Other Notes

Schildknecht, S., et al. 2014. Curr. Med. Chem.21, 365.
Laleu, B., et al. 2010. J. Med. Chem.53, 7715.
Sedeek, M., et al. 2010. Am. J. Physiol. Renal Physiol.299, F1348.

Legal Information

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

Disclaimer

Toxicity: Standard Handling (A)

Safety Information

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