| Structural highlights
3ln0 is a 4 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Gene: | Cox-2, Cox2, Pghs-b, prostaglandin H2 synthase 2, Ptgs2, Tis10 (LK3 transgenic mice) |
| Activity: | Prostaglandin-endoperoxide synthase, with EC number 1.14.99.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[PGH2_MOUSE] Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.[1] [2] [3] [4]
Publication Abstract from PubMed
In this Letter, we provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data for a series of selective COX-2 inhibitors. During the course of our structure-based drug design efforts, we discovered two distinct binding modes within the COX-2 active site for differently substituted members of this class. The challenge of a undesirably long human half-life for the first clinical candidate 1t(1/2)=360h was addressed by multiple strategies, leading to the discovery of 29b-(S) (SC-75416) with t(1/2)=34h.
The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life.,Wang JL, Limburg D, Graneto MJ, Springer J, Hamper JR, Liao S, Pawlitz JL, Kurumbail RG, Maziasz T, Talley JJ, Kiefer JR, Carter J Bioorg Med Chem Lett. 2010 Jul 24. PMID:20709553[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rowlinson SW, Kiefer JR, Prusakiewicz JJ, Pawlitz JL, Kozak KR, Kalgutkar AS, Stallings WC, Kurumbail RG, Marnett LJ. A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385. J Biol Chem. 2003 Nov 14;278(46):45763-9. Epub 2003 Aug 18. PMID:12925531 doi:http://dx.doi.org/10.1074/jbc.M305481200
- ↑ Vecchio AJ, Simmons DM, Malkowski MG. Structural basis of fatty acid substrate binding to cyclooxygenase-2. J Biol Chem. 2010 Jul 16;285(29):22152-63. Epub 2010 May 12. PMID:20463020 doi:10.1074/jbc.M110.119867
- ↑ Duggan KC, Walters MJ, Musee J, Harp JM, Kiefer JR, Oates JA, Marnett LJ. Molecular basis for cyclooxygenase inhibition by the non-steroidal anti-inflammatory drug naproxen. J Biol Chem. 2010 Nov 5;285(45):34950-9. Epub 2010 Sep 1. PMID:20810665 doi:10.1074/jbc.M110.162982
- ↑ Vecchio AJ, Malkowski MG. The structural basis of endocannabinoid oxygenation by cyclooxygenase-2. J Biol Chem. 2011 Jun 10;286(23):20736-45. Epub 2011 Apr 13. PMID:21489986 doi:10.1074/jbc.M111.230367
- ↑ Wang JL, Limburg D, Graneto MJ, Springer J, Hamper JR, Liao S, Pawlitz JL, Kurumbail RG, Maziasz T, Talley JJ, Kiefer JR, Carter J. The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life. Bioorg Med Chem Lett. 2010 Jul 24. PMID:20709553 doi:10.1016/j.bmcl.2010.07.054
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