2bhj | pdb_00002bhj
MURINE INO SYNTHASE WITH COUMARIN INHIBITOR
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| 2bhj, resolution 3.2Å | |||||||||||||
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| Sites: | AC1 | ||||||||||||
| Ligands: | FC1, HBI, HEM | ||||||||||||
| Activity: | Nitric-oxide synthase, with EC number 1.14.13.39 | ||||||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
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. 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
Page seeded by OCA on Mon Mar 31 02:06:30 2008
