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Updated: Feb 10, 2026

Primary Orthotopic Glioma Xenografts Recapitulate Infiltrative Growth and Isocitrate Dehydrogenase I Mutation
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Inhibition of Mutated Isocitrate Dehydrogenase 1 in Cancer

Fangrui Wu1, Gang Cheng1, Yuan Yao1

  • 1Department of Pharmacology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, United States.

Medicinal Chemistry (Shariqah (United Arab Emirates))
|May 25, 2018
PubMed
Abstract

Insights

Novel aromatic sulfonamides effectively inhibit the R132H mutation in isocitrate dehydrogenase 1 (IDH1), showing potent antitumor activity against glioma cells with this specific mutation.

Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Oncology

Background:

  • The R132H mutation in isocitrate dehydrogenase 1 (IDH1) is prevalent in gliomas and other cancers.
  • There is a need for diverse chemical classes of IDH1(R132H) inhibitors.

Purpose of the Study:

  • To develop a new class of potent IDH1(R132H) inhibitors.
  • To explore their potential as antitumor agents.

Main Methods:

  • Development of a biochemical assay for IDH1(R132H) inhibition.
  • Chemical synthesis and structure-activity relationship (SAR) studies.
  • Evaluation of antitumor activity in glioma cell lines.

Main Results:

  • A novel series of aromatic sulfonamides were identified as potent IDH1(R132H) inhibitors (Ki as low as 0.6 µM).
  • SAR studies guided compound optimization.
  • Selected inhibitors demonstrated high selectivity for mutant IDH1 over wild-type IDH1.
  • Two compounds potently inhibited proliferation of IDH1 R132H-mutated glioma cells without affecting wild-type cells.

Conclusions:

  • The identified aromatic sulfonamides represent a promising new class of IDH1(R132H) inhibitors.
  • These compounds hold potential for the development of novel glioma treatments targeting IDH1 mutations.
Keywords:
Aerobic metabolismenzyme inhibitorisocitrate dehydrogenasemedicinal chemistrymutationsoncogenic mutation.

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