Related Experiment Video

Updated: Mar 14, 2026

Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography
09:09

Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography

Published on: September 20, 2016

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Crystal structure of rofecoxib bound to human cyclooxygenase-2

Benjamin J Orlando1, Michael G Malkowski1

  • 1Department of Structural Biology, The State University of New York at Buffalo and the Hauptman-Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY 14203, USA.

Acta Crystallographica. Section F, Structural Biology Communications
|October 7, 2016
PubMed

Insights

Rofecoxib (Vioxx) binding to cyclooxygenase-2 (COX-2) was structurally determined. This reveals how Vioxx

Area of Science:

  • Biochemistry
  • Structural Biology
  • Pharmacology

Background:

  • Rofecoxib (Vioxx) was a selective cyclooxygenase-2 (COX-2) inhibitor (coxib) withdrawn due to cardiovascular risks.
  • The molecular mechanism of Vioxx binding to COX-2 remained largely unknown.
  • Vioxx's unique methyl sulfone moiety distinguishes it from other coxibs.

Purpose of the Study:

  • To elucidate the molecular-level binding of Vioxx to human COX-2.
  • To determine the crystal structure of human COX-2 in complex with Vioxx.

Main Methods:

  • Identification of novel crystallization conditions for human COX-2.
  • X-ray crystallography to determine the structure of the COX-2-Vioxx complex.
  • Structural analysis at 2.7 Å resolution.

Main Results:

  • The crystal structure of human COX-2 complexed with Vioxx was determined.
  • Atomic-level details of Vioxx binding to COX-2 are provided for the first time.
  • Vioxx binds via its methyl sulfone moiety in the COX-2 side pocket, supporting isoform selectivity.

Conclusions:

  • The study provides the first atomic resolution structure of Vioxx bound to COX-2.
  • The findings explain the binding mode and support the isoform selectivity of Vioxx.
  • Understanding this interaction may inform the design of safer COX-2 inhibitors.
Keywords:
Vioxxcrystal structurecyclooxygenasenonsteroidal anti-inflammatory drugsrofecoxib

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