Structure-Based Design and Identification of FT-2102 (Olutasidenib), a Potent Mutant-Selective IDH1 Inhibitor.

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Caravella JA, Lin J, Diebold RB, Campbell AM, Ericsson A, Gustafson G, Wang Z, Castro J, Clarke A, Gotur D, Josephine HR, Katz M, Kershaw M, Yao L, Toms AV, Barr KJ, Dinsmore CJ, Walker D, Ashwell S, Lu W

Structure-Based Design and Identification of FT-2102 (Olutasidenib), a Potent Mutant-Selective IDH1 Inhibitor.

J Med Chem. 2020 Feb 27;63(4):1612-1623. doi: 10.1021/acs.jmedchem.9b01423. Epub 2020 Feb 12.

PubMed ID

31971798 [ View in PubMed

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Abstract

Inhibition of mutant IDH1 is being evaluated clinically as a treatment option for oncology. Here we describe the structure-based design and optimization of quinoline lead compounds to identify FT-2102, a potent, orally bioavailable, brain penetrant, and selective mIDH1 inhibitor. FT-2102 has excellent ADME/PK properties and reduces 2-hydroxyglutarate levels in an mIDH1 xenograft tumor model. This compound has been selected as a candidate for clinical development in hematologic malignancies, solid tumors, and gliomas with mIDH1.

DrugBank Data that Cites this Article

Drugs

Olutasidenib

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Olutasidenib	Isocitrate dehydrogenase [NADP] cytoplasmic	Protein	Humans	Yes	Inhibitor	Details