Structure-based design of COX-2 selectivity into flurbiprofen.

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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

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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	Yes	Inhibitor	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Flurbiprofen	Prostaglandin G/H synthase 2	IC 50 (nM)	10	N/A	N/A	Details