Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

Nicholas Kwiatkowski, Tinghu Zhang, Peter B. Rahl, Brian J. Abraham, Jessica Reddy, Scott B. Ficarro, Anahita Dastur, Arnaud Amzallag, Sridhar Ramaswamy, Bethany Tesar, Catherine E. Jenkins, Nancy M. Hannett, Douglas McMillin, Takaomi Sanda, Taebo Sim, Nam Doo Kim, Thomas Look, Constantine S. Mitsiades, Andrew P. Weng, Jennifer R. Brown, Cyril H. Benes, Jarrod A. Marto, Richard A. Young () and Nathanael S. Gray ()
Additional contact information
Nicholas Kwiatkowski: Dana-Farber Cancer Institute
Tinghu Zhang: Dana-Farber Cancer Institute
Peter B. Rahl: Whitehead Institute for Biomedical Research, 9 Cambridge Center
Brian J. Abraham: Whitehead Institute for Biomedical Research, 9 Cambridge Center
Jessica Reddy: Whitehead Institute for Biomedical Research, 9 Cambridge Center
Scott B. Ficarro: Dana-Farber Cancer Institute
Anahita Dastur: Department of Medicine Massachusetts General Hospital Cancer Center and Harvard Medical School
Arnaud Amzallag: Department of Medicine Massachusetts General Hospital Cancer Center and Harvard Medical School
Sridhar Ramaswamy: Department of Medicine Massachusetts General Hospital Cancer Center and Harvard Medical School
Bethany Tesar: Dana-Farber Cancer Institute, Harvard Medical School
Catherine E. Jenkins: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada
Nancy M. Hannett: Whitehead Institute for Biomedical Research, 9 Cambridge Center
Douglas McMillin: Dana-Farber Cancer Institute, Harvard Medical School
Takaomi Sanda: Dana-Farber Cancer Institute, Harvard Medical School
Taebo Sim: Chemical Kinomics Research Center, Korea Institute of Science and Technology, 39-1, Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Korea, and KU-KIST Graduate School of Converging Science and Technology, 145, Anam-ro, Seongbuk-gu, Seoul 136-713, Korea
Nam Doo Kim: Daegu-Gyeongbuk Medical Innovation Foundation, 2387 dalgubeol-daero, Suseong-gu, Daegu 706-010, Korea
Thomas Look: Dana-Farber Cancer Institute, Harvard Medical School
Constantine S. Mitsiades: Dana-Farber Cancer Institute, Harvard Medical School
Andrew P. Weng: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada
Jennifer R. Brown: Dana-Farber Cancer Institute, Harvard Medical School
Cyril H. Benes: Department of Medicine Massachusetts General Hospital Cancer Center and Harvard Medical School
Jarrod A. Marto: Dana-Farber Cancer Institute
Richard A. Young: Whitehead Institute for Biomedical Research, 9 Cambridge Center
Nathanael S. Gray: Dana-Farber Cancer Institute

Nature, 2014, vol. 511, issue 7511, 616-620

Abstract: Here, a covalent inhibitor targeting cyclin-dependent kinase 7 (CDK7) demonstrates in vitro and in vivo efficacy against T-cell acute lymphoblastic leukaemia by downregulating oncogenic transcriptional programs.

Date: 2014
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DOI: 10.1038/nature13393

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