2BHJ

murine iNO synthase with coumarin inhibitor

Summary for 2BHJ

• Entry DOI: 10.2210/pdb2bhj/pdb
• Related: 1DD7 1DF1 1DWV 1DWW 1DWX 1JWJ 1JWK 1M8D 1M8E 1M8H 1M8I 1M9T 1N2N 1NOC 1NOD 1NOS 1QOM 1QW4 1QW5 1R35 1VAF 2NOD 2NOS 3NOD
• Descriptor: NITRIC OXIDE SYNTHASE, THIOCOUMARIN, PROTOPORPHYRIN IX CONTAINING FE, ... (5 entities in total)
• Functional Keywords: inos, calmodulin-binding, fad, fmn, heme, metal-binding, nadp, oxidoreductase, polymorphism, zinc
• Biological source: MUS MUSCULUS (MOUSE)
• Total number of polymer chains: 1
• Total formula weight: 49988.59

Authors

Mathieu, M.,Guilloteau, J.P. (deposition date: 2005-01-12, release date: 2005-03-31, Last modification date: 2024-10-16)

Primary citation

Jackson, S.A.,Sahni, S.,Lee, L.,Luo, Y.,Nieduzak, T.R.,Liang, G.,Chiang, Y.,Collar, N.,Fink, D.,He, W.,Laoui, A.,Merrill, J.,Boffey, R.,Crackett, P.,Rees, B.,Wong, M.,Guilloteau, J.P.,Mathieu, M.,Rebello, S.S.
Design, Synthesis and Characterization of a Novel Class of Coumarin-Based Inhibitors of Inducible Nitric Oxide Synthase
Bioorg.Med.Chem., 13:2723-, 2005

PubMed Abstract: 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.

PubMed: 15781384
DOI: 10.1016/J.BMC.2005.02.036

Experimental method

X-RAY DIFFRACTION (3.2 Å)