Literature DB >> 24900389

Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG in Vivo.

Janeta Popovici-Muller1, Jeffrey O Saunders2, Francesco G Salituro3, Jeremy M Travins1, Shunqi Yan4, Fang Zhao5, Stefan Gross1, Lenny Dang1, Katharine E Yen1, Hua Yang1, Kimberly S Straley1, Shengfang Jin1, Kaiko Kunii1, Valeria R Fantin6, Shunan Zhang7, Qiongqun Pan7, Derek Shi7, Scott A Biller1, Shinsan M Su1.   

Abstract

Optimization of a series of R132H IDH1 inhibitors from a high throughput screen led to the first potent molecules that show robust tumor 2-HG inhibition in a xenograft model. Compound 35 shows good potency in the U87 R132H cell based assay and ∼90% tumor 2-HG inhibition in the corresponding mouse xenograft model following BID dosing. The magnitude and duration of tumor 2-HG inhibition correlates with free plasma concentration.

Entities:  

Keywords:  Mutant IDH1; R132H IDH1 inhibitors; tumor 2-HG

Year:  2012        PMID： 24900389      PMCID： PMC4025665          DOI： 10.1021/ml300225h

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  13 in total

1.  The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases.

Authors:  Rasheduzzaman Chowdhury; Kar Kheng Yeoh; Ya-Min Tian; Lars Hillringhaus; Eleanor A Bagg; Nathan R Rose; Ivanhoe K H Leung; Xuan S Li; Esther C Y Woon; Ming Yang; Michael A McDonough; Oliver N King; Ian J Clifton; Robert J Klose; Timothy D W Claridge; Peter J Ratcliffe; Christopher J Schofield; Akane Kawamura
Journal:  EMBO Rep       Date:  2011-04-01       Impact factor: 8.807

2.  IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics.

Authors:  Masato Sasaki; Christiane B Knobbe; Joshua C Munger; Evan F Lind; Dirk Brenner; Anne Brüstle; Isaac S Harris; Roxanne Holmes; Andrew Wakeham; Jillian Haight; Annick You-Ten; Wanda Y Li; Stefanie Schalm; Shinsan M Su; Carl Virtanen; Guido Reifenberger; Pamela S Ohashi; Dwayne L Barber; Maria E Figueroa; Ari Melnick; Juan-Carlos Zúñiga-Pflücker; Tak W Mak
Journal:  Nature       Date:  2012-08-30       Impact factor: 49.962

3.  Cancer-associated IDH1 mutations produce 2-hydroxyglutarate.

Authors:  Lenny Dang; David W White; Stefan Gross; Bryson D Bennett; Mark A Bittinger; Edward M Driggers; Valeria R Fantin; Hyun Gyung Jang; Shengfang Jin; Marie C Keenan; Kevin M Marks; Robert M Prins; Patrick S Ward; Katharine E Yen; Linda M Liau; Joshua D Rabinowitz; Lewis C Cantley; Craig B Thompson; Matthew G Vander Heiden; Shinsan M Su
Journal:  Nature       Date:  2009-12-10       Impact factor: 49.962

4.  An integrated genomic analysis of human glioblastoma multiforme.

Authors:  D Williams Parsons; Siân Jones; Xiaosong Zhang; Jimmy Cheng-Ho Lin; Rebecca J Leary; Philipp Angenendt; Parminder Mankoo; Hannah Carter; I-Mei Siu; Gary L Gallia; Alessandro Olivi; Roger McLendon; B Ahmed Rasheed; Stephen Keir; Tatiana Nikolskaya; Yuri Nikolsky; Dana A Busam; Hanna Tekleab; Luis A Diaz; James Hartigan; Doug R Smith; Robert L Strausberg; Suely Kazue Nagahashi Marie; Sueli Mieko Oba Shinjo; Hai Yan; Gregory J Riggins; Darell D Bigner; Rachel Karchin; Nick Papadopoulos; Giovanni Parmigiani; Bert Vogelstein; Victor E Velculescu; Kenneth W Kinzler
Journal:  Science       Date:  2008-09-04       Impact factor: 47.728

5.  IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype.

Authors:  Sevin Turcan; Daniel Rohle; Anuj Goenka; Logan A Walsh; Fang Fang; Emrullah Yilmaz; Carl Campos; Armida W M Fabius; Chao Lu; Patrick S Ward; Craig B Thompson; Andrew Kaufman; Olga Guryanova; Ross Levine; Adriana Heguy; Agnes Viale; Luc G T Morris; Jason T Huse; Ingo K Mellinghoff; Timothy A Chan
Journal:  Nature       Date:  2012-02-15       Impact factor: 69.504

6.  Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases.

Authors:  Wei Xu; Hui Yang; Ying Liu; Ying Yang; Ping Wang; Se-Hee Kim; Shinsuke Ito; Chen Yang; Pu Wang; Meng-Tao Xiao; Li-xia Liu; Wen-qing Jiang; Jing Liu; Jin-ye Zhang; Bin Wang; Stephen Frye; Yi Zhang; Yan-hui Xu; Qun-ying Lei; Kun-Liang Guan; Shi-min Zhao; Yue Xiong
Journal:  Cancer Cell       Date:  2011-01-18       Impact factor: 38.585

Review 7.  Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism.

Authors:  Zachary J Reitman; Hai Yan
Journal:  J Natl Cancer Inst       Date:  2010-05-31       Impact factor: 11.816

8.  IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication.

Authors:  Peter Paschka; Richard F Schlenk; Verena I Gaidzik; Marianne Habdank; Jan Krönke; Lars Bullinger; Daniela Späth; Sabine Kayser; Manuela Zucknick; Katharina Götze; Heinz-A Horst; Ulrich Germing; Hartmut Döhner; Konstanze Döhner
Journal:  J Clin Oncol       Date:  2010-06-21       Impact factor: 50.717

Review 9.  Cancer-associated IDH mutations: biomarker and therapeutic opportunities.

Authors:  K E Yen; M A Bittinger; S M Su; V R Fantin
Journal:  Oncogene       Date:  2010-10-25       Impact factor: 8.756

10.  IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours.

Authors:  M Fernanda Amary; Krisztian Bacsi; Francesca Maggiani; Stephen Damato; Dina Halai; Fitim Berisha; Robin Pollock; Paul O'Donnell; Anita Grigoriadis; Tim Diss; Malihe Eskandarpour; Nadège Presneau; Pancras Cw Hogendoorn; Andrew Futreal; Roberto Tirabosco; Adrienne M Flanagan
Journal:  J Pathol       Date:  2011-05-19       Impact factor: 9.883
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  91 in total

1.  Genetic dissection of leukemia-associated IDH1 and IDH2 mutants and D-2-hydroxyglutarate in Drosophila.

Authors:  Zachary J Reitman; Sergey A Sinenko; Eric P Spana; Hai Yan
Journal:  Blood       Date:  2014-11-14       Impact factor: 22.113

Review 2.  Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate.

Authors:  Ovidiu C Andronesi; Otto Rapalino; Elizabeth Gerstner; Andrew Chi; Tracy T Batchelor; Dan P Cahill; A Gregory Sorensen; Bruce R Rosen
Journal:  J Clin Invest       Date:  2013-09-03       Impact factor: 14.808

3.  Non-invasive in vivo assessment of IDH1 mutational status in glioma.

Authors:  Myriam M Chaumeil; Peder E Z Larson; Hikari A I Yoshihara; Olivia M Danforth; Daniel B Vigneron; Sarah J Nelson; Russell O Pieper; Joanna J Phillips; Sabrina M Ronen
Journal:  Nat Commun       Date:  2013       Impact factor: 14.919

4.  Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Allosteric and Mutant Specific Inhibitors of IDH1.

Authors:  Julian R Levell; Thomas Caferro; Gregg Chenail; Ina Dix; Julia Dooley; Brant Firestone; Pascal D Fortin; John Giraldes; Ty Gould; Joseph D Growney; Michael D Jones; Raviraj Kulathila; Fallon Lin; Gang Liu; Arne Mueller; Simon van der Plas; Kelly Slocum; Troy Smith; Remi Terranova; B Barry Touré; Viraj Tyagi; Trixie Wagner; Xiaoling Xie; Ming Xu; Fan S Yang; Liping X Zhou; Raymond Pagliarini; Young Shin Cho
Journal:  ACS Med Chem Lett       Date:  2016-12-16       Impact factor: 4.345

5.  Inhibition of Mutated Isocitrate Dehydrogenase 1 in Cancer.

Authors:  Fangrui Wu; Gang Cheng; Yuan Yao; Mari Kogiso; Hong Jiang; Xiao-Nan Li; Yongcheng Song
Journal:  Med Chem       Date:  2018       Impact factor: 2.745

6.  Synthesis and Evaluation of a 18F-Labeled Triazinediamine Analogue for Imaging Mutant IDH1 Expression in Gliomas by PET.

Authors:  Satish K Chitneni; Hai Yan; Michael R Zalutsky
Journal:  ACS Med Chem Lett       Date:  2018-05-01       Impact factor: 4.345

7.  Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Orally Bioavailable and Brain Penetrant Mutant IDH1 Inhibitors.

Authors:  Qian Zhao; James R Manning; James Sutton; Abran Costales; Martin Sendzik; Cynthia M Shafer; Julian R Levell; Gang Liu; Thomas Caferro; Young Shin Cho; Mark Palermo; Gregg Chenail; Julia Dooley; Brian Villalba; Ali Farsidjani; Jinyun Chen; Stephanie Dodd; Ty Gould; Guiqing Liang; Kelly Slocum; Minying Pu; Brant Firestone; Joseph Growney; Tycho Heimbach; Raymond Pagliarini
Journal:  ACS Med Chem Lett       Date:  2018-06-11       Impact factor: 4.345

8.  A high-throughput SAMDI-mass spectrometry assay for isocitrate dehydrogenase 1.

Authors:  Sarah E Anderson; Natalie S Fahey; Jungsoo Park; Patrick T O'Kane; Chad A Mirkin; Milan Mrksich
Journal:  Analyst       Date:  2020-04-16       Impact factor: 4.616

9.  Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases by 2-Thiohydantoin Compounds.

Authors:  Fangrui Wu; Hong Jiang; Baisong Zheng; Mari Kogiso; Yuan Yao; Chao Zhou; Xiao-Nan Li; Yongcheng Song
Journal:  J Med Chem       Date:  2015-08-26       Impact factor: 7.446

Review 10.  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
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