Structure-based design of COX-2 selectivity into flurbiprofen.
Article Details
- CitationCopy to clipboard
Bayly CI, Black WC, Leger S, Ouimet N, Ouellet M, Percival MD
Structure-based design of COX-2 selectivity into flurbiprofen.
Bioorg Med Chem Lett. 1999 Feb 8;9(3):307-12.
- PubMed ID
- 10091674 [ View in PubMed]
- Abstract
Comparative computer modeling of the X-ray crystal structures of cyclooxygenase isoforms COX-1 and COX-2 has led to the design of COX-2 selectivity into the nonselective inhibitor flurbiprofen. The COX-2 modeling was based on a postulated binding mode for flurbiprofen and took advantage of a small alcove in the COX-2 active site created by different positions of the Leu384 sidechain between COX-1 and COX-2. The design hypothesis was tested by synthesis and biological assay of a series of flurbiprofen analogs, culminating in the discovery of several inhibitors having up to 78-fold selectivity for COX-2 over COX-1.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Flurbiprofen Prostaglandin G/H synthase 2 Protein Humans YesInhibitorDetails - Binding Properties
Drug Target Property Measurement pH Temperature (°C) Flurbiprofen Prostaglandin G/H synthase 2 IC 50 (nM) 10 N/A N/A Details