ArticleMedicinal chemistry (Shariqah (United Arab Emirates))2018
Inhibition of Mutated Isocitrate Dehydrogenase 1 in Cancer.
Article in Medicinal chemistry (Shariqah (United Arab Emirates)), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- Review
- Epigenetic modification and characterization of theFrontiers in oncology · 2024Article
- Recent advances of IDH1 mutant inhibitor in cancer therapy.Frontiers in pharmacology · 2022Review
- Novel IDH1-Targeted Glioma Therapies.CNS drugs · 2019Article
- Contribution of the Wnt Pathway to Defining Biology of Glioblastoma.Neuromolecular medicine · 2018Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
backgroundR132H mutation of isocitrate dehydrogenase 1 (IDH1) is found in ~75% of low-grade gliomas and secondary glioblastomas as well as in several other types of cancer. More chemotypes of inhibitors of IDH1(R132H) are therefore needed.
objectiveThe study aimed to develop a new class of IDH1(R132H) inhibitors as potent antitumor agents.
methodA biochemical assay was developed to find inhibitors of IDH1(R132H) mutant enzyme. Chemical synthesis and structure-activity relationship studies were used to find compounds with improved potency. Antitumor activities of selected compounds were evaluated.
resultsA series of aromatic sulfonamide compounds was found to be novel, potent inhibitors of IDH1(R132H) with Ki values as low as 0.6 µM. Structure-activity relationships of these compounds are discussed. Enzyme kinetics studies showed that one compound is a competitive inhibitor against the substrate α-KG and a non-competitive inhibitor against the cofactor NADPH. Several inhibitors were found to have no activity against wild-type IDH1, showing a high selectivity. Two potent inhibitors exhibited strong activity against proliferation of BT142 glioma cells with IDH1 R132H mutation, while these compounds did not significantly affect the growth of glioma cells without IDH1 mutation.
conclusionThis novel series of IDH1(R132H) inhibitors have potential to be further developed for the treatment of glioma with IDH1 mutation.
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Registered trials
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