Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

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

C I Bayly1, W C Black, S Léger

  • 1Merck Frosst Canada Inc., Pointe-Claire-Dorval, Quebec, Canada.

Bioorganic & Medicinal Chemistry Letters
|March 26, 1999
PubMed
Summary

Researchers designed selective cyclooxygenase-2 (COX-2) inhibitors by modifying flurbiprofen. Computer modeling identified a key structural difference, leading to analogs with up to 78-fold COX-2 selectivity over COX-1.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Exploring Occlusal Caries Management over 2 Decades in France among General Dental Practitioners.

JDR clinical and translational research·2025
Same author

Regression trees to identify combinations of farming practices that achieve the best overall intrinsic quality of milk.

Journal of dairy science·2022
Same author

Validation of the 'EPICES' social deprivation score in a population of women who have just given birth: a French cross-sectional study.

Public health·2021
Same author

Vector-apodizing phase plate coronagraph: design, current performance, and future development [Invited].

Applied optics·2021
Same author

COgnitive enhancement and consumption of psychoactive Substances among Youth Students (COSYS): a cross-sectional study in France.

Public health·2021
Same author

Exome-wide association of deltamethrin resistance in Aedes aegypti from Mexico.

Insect molecular biology·2019

Area of Science:

  • Medicinal Chemistry
  • Computational Biology
  • Pharmacology

Background:

  • Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are enzymes involved in inflammation and pain.
  • Nonselective inhibitors like flurbiprofen target both isoforms, leading to potential side effects.
  • Selective COX-2 inhibitors offer a therapeutic advantage by reducing gastrointestinal toxicity.

Purpose of the Study:

  • To design and synthesize novel flurbiprofen analogs with enhanced selectivity for COX-2 over COX-1.
  • To utilize comparative computer modeling of enzyme crystal structures to guide inhibitor design.

Main Methods:

  • Comparative X-ray crystal structure modeling of COX-1 and COX-2 active sites.
  • Structure-based drug design focusing on the Leu384 sidechain interaction.

Related Experiment Videos

  • Chemical synthesis of flurbiprofen analogs.
  • In vitro biological assays to determine inhibitory activity and selectivity.

    • Main Results:

    • Computer modeling revealed a small active site pocket in COX-2 due to Leu384 positioning, exploitable for selective inhibition.
    • A series of flurbiprofen analogs were synthesized and tested.
    • Several analogs demonstrated significant selectivity for COX-2, with one exhibiting up to 78-fold selectivity over COX-1.

    Conclusions:

    • Structure-based design, guided by computational modeling, is effective in developing selective COX-2 inhibitors.
    • Flurbiprofen can be modified to achieve high COX-2 selectivity, offering potential for improved anti-inflammatory therapies with reduced side effects.