2bhj
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Inducible nitric oxide synthase (iNOS) has been implicated in various | + | 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== | ==About this Structure== | ||
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[[Category: Nitric-oxide synthase]] | [[Category: Nitric-oxide synthase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Guilloteau, J | + | [[Category: Guilloteau, J P.]] |
[[Category: Mathieu, M.]] | [[Category: Mathieu, M.]] | ||
[[Category: FC1]] | [[Category: FC1]] | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:37:51 2008'' |
Revision as of 14:37, 21 February 2008
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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 , and as ligands. Active as Nitric-oxide synthase, with EC number 1.14.13.39 Known structural/functional Site: . 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 Thu Feb 21 16:37:51 2008
Categories: Mus musculus | Nitric-oxide synthase | Single protein | Guilloteau, J P. | Mathieu, M. | FC1 | HBI | HEM | Calmodulin-binding | Fad | Fmn | Heme | Inos | Metal-binding | Nadp | Oxidoreductase | Polymorphism | Zinc
