Kinetic-based high-throughput screening assay to discover novel classes of macrophage migration inhibitory factor inhibitors

Hajer Ouertatani-Sakouhi, Min Liu, Farah El-Turk, Gregory D. Cuny, Marcie A. Glicksman, Hilala Lashuel

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Macrophage migration inhibitory factor (MIF) is a major mediator of innate immunity and inflammation and presents a potential therapeutic target for various inflammatory, infectious, and autoimmune diseases, including cancer. Although a number of inhibitors have been identified and designed based on the modification of known nonphysiological substrates, the lack of a suitable high-throughput assay has hindered the screening of chemical libraries and the discovery of more diverse inhibitors. Herein the authors report the development and optimization of a robust high-throughput kinetic-based activity assay for the identification of new MIF inhibitors. Using this assay, they screened 80,000 small molecules and identified and validated 13 novel inhibitors of MIF catalytic activity. These small molecules demonstrated inhibition constant (Ki,app) values ranging from 0.5 to 13 μM.

Original languageEnglish
Pages (from-to)347-358
Number of pages12
JournalJournal of Biomolecular Screening
Volume15
Issue number4
DOIs
Publication statusPublished - 1 Apr 2010
Externally publishedYes

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Keywords

  • High throughput screening
  • HTS
  • Inflammatory diseases
  • Macrophage migration inhibitory factor
  • MIF
  • Tautomerase activity

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmacology
  • Biochemistry
  • Molecular Medicine
  • Biotechnology

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