3MQE

Structure of SC-75416 bound at the COX-2 active site

Summary for 3MQE

• Entry DOI: 10.2210/pdb3mqe/pdb
• Related: 1PXX 3LN1
• Related PRD ID: PRD_900017
• Descriptor: Prostaglandin G/H synthase 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-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: 278000.44

Authors

Wang, J.L.,Limburg, D.,Graneto, M.J.,Springer, J.,Rogier, J.,Kiefer, J.R. (deposition date: 2010-04-28, release date: 2010-10-27, Last modification date: 2024-10-30)

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 (2.8 Å)