2bhj

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spinqualitylabelsall models 2bhj, resolution 3.2Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

MURINE INO SYNTHASE WITH COUMARIN INHIBITOR

Overview

Inducible nitric oxide synthase (iNOS) has been implicated in various, central and peripheral pathophysiological diseases. Our high throughput, screening initially identified a weak inhibitor of iNOS, thiocoumarin 13., From this lead, a number of potent derivatives were prepared that, demonstrate favorable potency, selectivity and kinetics. Compound 30 has, an IC50 of 60 nM for mouse iNOS and 185-fold and 9-fold selectivity for, bovine eNOS and rat nNOS, respectively. In cellular assays for iNOS, this, compound has micromolar potency. Furthermore, two compounds (16 and 30), demonstrate a reasonable pharmacokinetic profile in rodents. The, synthesis, SAR, and biological activity of this novel class of compounds, is described.

About this Structure

2BHJ is a [Single protein] structure of sequence from [Mus musculus] with FC1, HEM and HBI as [ligands]. Active as [[1]], with EC number [1.14.13.39]. Full crystallographic information is available from [OCA].

Reference

Design, synthesis and characterization of a novel class of coumarin-based inhibitors of inducible nitric oxide synthase., Jackson SA, Sahni S, Lee L, Luo Y, Nieduzak TR, Liang G, Chiang Y, Collar N, Fink D, He W, Laoui A, Merrill J, Boffey R, Crackett P, Rees B, Wong M, Guilloteau JP, Mathieu M, Rebello SS, Bioorg Med Chem. 2005 Apr 15;13(8):2723-39. PMID:15781384

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