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Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

Author

Listed:
  • Nicholas Kwiatkowski

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Whitehead Institute for Biomedical Research, 9 Cambridge Center)

  • Tinghu Zhang

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • 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
    Massachusetts Institute of Technology)

  • Scott B. Ficarro

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Blais Proteomics Center, 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
    Broad Institute of MIT and Harvard, 7 Cambridge Center)

  • Sridhar Ramaswamy

    (Department of Medicine Massachusetts General Hospital Cancer Center and Harvard Medical School
    Broad Institute of MIT and Harvard, 7 Cambridge Center)

  • Bethany Tesar

    (Dana-Farber Cancer Institute, Harvard Medical School
    Brigham and Women’s Hospital, 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
    Brigham and Women’s Hospital, Harvard Medical School)

  • Takaomi Sanda

    (Dana-Farber Cancer Institute, Harvard Medical School
    Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore)

  • 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
    Children’s Hospital)

  • Constantine S. Mitsiades

    (Dana-Farber Cancer Institute, Harvard Medical School
    Brigham and Women’s Hospital, 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
    Brigham and Women’s Hospital, 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
    Harvard Medical School
    Blais Proteomics Center, Dana-Farber Cancer Institute)

  • Richard A. Young

    (Whitehead Institute for Biomedical Research, 9 Cambridge Center
    Massachusetts Institute of Technology)

  • Nathanael S. Gray

    (Dana-Farber Cancer Institute
    Harvard Medical School)

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.

Suggested Citation

  • 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 , 2014. "Targeting transcription regulation in cancer with a covalent CDK7 inhibitor," Nature, Nature, vol. 511(7511), pages 616-620, July.
    • Handle: RePEc:nat:nature:v:511:y:2014:i:7511:d:10.1038_nature13393
    DOI: 10.1038/nature13393
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    Citations

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    Cited by:

    1. Jayden Sterling & Jennifer R. Baker & Adam McCluskey & Lenka Munoz, 2023. "Systematic literature review reveals suboptimal use of chemical probes in cell-based biomedical research," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Ádám Levente Póti & Dániel Bálint & Anita Alexa & Péter Sok & Kristóf Ozsváth & Krisztián Albert & Gábor Turczel & Sarolt Magyari & Orsolya Ember & Kinga Papp & Sándor Balázs Király & Tímea Imre & Kri, 2024. "Targeting a key protein-protein interaction surface on mitogen-activated protein kinases by a precision-guided warhead scaffold," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    3. Barbara Steurer & Roel C. Janssens & Marit E. Geijer & Fernando Aprile-Garcia & Bart Geverts & Arjan F. Theil & Barbara Hummel & Martin E. Royen & Bastiaan Evers & René Bernards & Adriaan B. Houtsmull, 2022. "DNA damage-induced transcription stress triggers the genome-wide degradation of promoter-bound Pol II," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Austin Hsu & Qiming Duan & Daniel S. Day & Xin Luo & Sarah McMahon & Yu Huang & Zachary B. Feldman & Zhen Jiang & Tinghu Zhang & Yanke Liang & Michael Alexanian & Arun Padmanabhan & Jonathan D. Brown , 2022. "Targeting transcription in heart failure via CDK7/12/13 inhibition," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Thibault Houles & Geneviève Lavoie & Sami Nourreddine & Winnie Cheung & Éric Vaillancourt-Jean & Célia M. Guérin & Mathieu Bouttier & Benoit Grondin & Sichun Lin & Marc K. Saba-El-Leil & Stephane Ange, 2022. "CDK12 is hyperactivated and a synthetic-lethal target in BRAF-mutated melanoma," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Tengfei Wang & Shuxiang Shi & Yuanyuan Shi & Peipei Jiang & Ganlu Hu & Qinying Ye & Zhan Shi & Kexin Yu & Chenguang Wang & Guoping Fan & Suwen Zhao & Hanhui Ma & Alex C. Y. Chang & Zhi Li & Qian Bian , 2023. "Chemical-induced phase transition and global conformational reorganization of chromatin," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. Victoria I. Cushing & Adrian F. Koh & Junjie Feng & Kaste Jurgaityte & Alexander Bondke & Sebastian H. B. Kroll & Marion Barbazanges & Bodo Scheiper & Ash K. Bahl & Anthony G. M. Barrett & Simak Ali &, 2024. "High-resolution cryo-EM of the human CDK-activating kinase for structure-based drug design," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Jieqiong Zhang & Zhenhua Hu & Hwa Hwa Chung & Yun Tian & Kah Weng Lau & Zheng Ser & Yan Ting Lim & Radoslaw M. Sobota & Hwei Fen Leong & Benjamin Jieming Chen & Clarisse Jingyi Yeo & Shawn Ying Xuan T, 2023. "Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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