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Literature DB >> 31971798

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

Justin A Caravella¹, Jian Lin¹, R Bruce Diebold¹, Ann-Marie Campbell², Anna Ericsson¹, Gary Gustafson², Zhongguo Wang¹, Jennifer Castro¹, Andrea Clarke¹, Deepali Gotur¹, Helen R Josephine¹, Marie Katz¹, Mark Kershaw², Lili Yao², Angela V Toms¹, Kenneth J Barr¹, Christopher J Dinsmore¹, Duncan Walker¹, Susan Ashwell¹, Wei Lu¹.

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.

Entities: Chemical Disease Gene

Year: 2020 PMID： 31971798 DOI： 10.1021/acs.jmedchem.9b01423

Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446

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Cited

28 in total

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Journal: Am J Cancer Res Date: 2020-12-01 Impact factor: 6.166

Review 2. Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy.

Authors: Jenna L Carter; Katie Hege; Jay Yang; Hasini A Kalpage; Yongwei Su; Holly Edwards; Maik Hüttemann; Jeffrey W Taub; Yubin Ge
Journal: Signal Transduct Target Ther Date: 2020-12-18

3. Diminishing GSH-Adduct Formation of Tricyclic Diazepine-based Mutant IDH1 Inhibitors.

Authors: Chunhui Huang; Christian Fischer; Michelle R Machacek; Stephane Bogen; Tesfaye Biftu; Xianhai Huang; Michael H Reutershan; Ryan Otte; Qingmei Hong; Zhicai Wu; Yang Yu; Min Park; Lei Chen; Purakkattle Biju; Ian Knemeyer; Ping Lu; Christopher J Kochansky; Michael Brendan Hicks; Yong Liu; Roy Helmy; Xavier Fradera; Anthony Donofrio; Josh Close; Matthew L Maddess; Catherine White; David L Sloman; Nunzio Sciammetta; Jun Lu; Craig Gibeau; Vladimir Simov; Hongjun Zhang; Peter Fuller; David Witter
Journal: ACS Med Chem Lett Date: 2022-03-28 Impact factor: 4.345

Review 4. Glioma-Targeted Therapeutics: Computer-Aided Drug Design Prospective.

Authors: Preantha Poonan; Clement Agoni; Mahmoud A A Ibrahim; Mahmoud E S Soliman
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Review 5. Glioblastoma: Current Status, Emerging Targets, and Recent Advances.

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Journal: J Med Chem Date: 2022-07-05 Impact factor: 8.039

Review 6. The implications of IDH mutations for cancer development and therapy.

Authors: Christopher J Pirozzi; Hai Yan
Journal: Nat Rev Clin Oncol Date: 2021-06-15 Impact factor: 66.675

7. Discovery and Optimization of 2H-1λ²-Pyridin-2-one Inhibitors of Mutant Isocitrate Dehydrogenase 1 for the Treatment of Cancer.

Authors: Jason M Rohde; Surendra Karavadhi; Rajan Pragani; Li Liu; Yuhong Fang; Weihe Zhang; Andrew McIver; Hongchao Zheng; Qingyang Liu; Mindy I Davis; Daniel J Urban; Tobie D Lee; Dorian M Cheff; Melinda Hollingshead; Mark J Henderson; Natalia J Martinez; Kyle R Brimacombe; Adam Yasgar; Wei Zhao; Carleen Klumpp-Thomas; Sam Michael; Joseph Covey; William J Moore; Gordon M Stott; Zhuyin Li; Anton Simeonov; Ajit Jadhav; Stephen Frye; Matthew D Hall; Min Shen; Xiaodong Wang; Samarjit Patnaik; Matthew B Boxer
Journal: J Med Chem Date: 2021-04-06 Impact factor: 7.446

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

Review 1. Non-coding RNAs: emerging regulators of glucose metabolism in hepatocellular carcinoma.

Review 2. Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy.

3. Diminishing GSH-Adduct Formation of Tricyclic Diazepine-based Mutant IDH1 Inhibitors.

Review 4. Glioma-Targeted Therapeutics: Computer-Aided Drug Design Prospective.

Review 5. Glioblastoma: Current Status, Emerging Targets, and Recent Advances.

Review 6. The implications of IDH mutations for cancer development and therapy.

7. Discovery and Optimization of 2H-1λ²-Pyridin-2-one Inhibitors of Mutant Isocitrate Dehydrogenase 1 for the Treatment of Cancer.

Review 8. Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation.

Review 9. Acute myeloid leukemia with IDH1 and IDH2 mutations: 2021 treatment algorithm.

Review 10. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.

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

Review 1. Non-coding RNAs: emerging regulators of glucose metabolism in hepatocellular carcinoma.

Review 2. Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy.

3. Diminishing GSH-Adduct Formation of Tricyclic Diazepine-based Mutant IDH1 Inhibitors.

Review 4. Glioma-Targeted Therapeutics: Computer-Aided Drug Design Prospective.

Review 5. Glioblastoma: Current Status, Emerging Targets, and Recent Advances.

Review 6. The implications of IDH mutations for cancer development and therapy.

7. Discovery and Optimization of 2H-1λ2-Pyridin-2-one Inhibitors of Mutant Isocitrate Dehydrogenase 1 for the Treatment of Cancer.

Review 8. Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation.

Review 9. Acute myeloid leukemia with IDH1 and IDH2 mutations: 2021 treatment algorithm.

Review 10. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.

7. Discovery and Optimization of 2H-1λ²-Pyridin-2-one Inhibitors of Mutant Isocitrate Dehydrogenase 1 for the Treatment of Cancer.