3NTG

Crystal structure of COX-2 with selective compound 23d-(R)

Summary for 3NTG

• Entry DOI: 10.2210/pdb3ntg/pdb
• Related: 1PXX 3LN0 3LN1 3MQE 3PGH
• Descriptor: Prostaglandin G/H synthase 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, PROTOPORPHYRIN IX CONTAINING FE, ... (7 entities in total)
• Functional Keywords: cox2, cox-2, pgh2s-2, cyclooxygenase-2, dioxygenase, disulfide bond, endoplasmic reticulum, fatty acid biosynthesis, glycoprotein, heme, iron, lipid synthesis, membrane, metal-binding, microsome, oxidoreductase, peroxidase, phosphoprotein, prostaglandin biosynthesis
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 4
• Total formula weight: 261163.46

Authors

Wang, J.L.,Limburg, D.,Graneto, M.J.,Carter, J.C.,Talley, J.J.,Kiefer, J.R. (deposition date: 2010-07-04, release date: 2010-10-27, Last modification date: 2024-11-20)

Primary citation

Wang, J.L.,Limburg, D.,Graneto, M.J.,Springer, J.,Hamper, J.R.,Liao, S.,Pawlitz, J.L.,Kurumbail, R.G.,Maziasz, T.,Talley, J.J.,Kiefer, J.R.,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., 20:7159-7163, 2010

PubMed Abstract: 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)=360 h was addressed by multiple strategies, leading to the discovery of 29b-(S) (SC-75416) with t(1/2)=34 h.

PubMed: 20709553
DOI: 10.1016/j.bmcl.2010.07.054

Experimental method

X-RAY DIFFRACTION (2.19 Å)