Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors

被引：0
|
作者：
Tinghu Zhang
Nicholas Kwiatkowski
Calla M Olson
Sarah E Dixon-Clarke
Brian J Abraham
Ann K Greifenberg
Scott B Ficarro
Jonathan M Elkins
Yanke Liang
Nancy M Hannett
Theresa Manz
Mingfeng Hao
Bartlomiej Bartkowiak
Arno L Greenleaf
Jarrod A Marto
Matthias Geyer
Alex N Bullock
Richard A Young
Nathanael S Gray
机构：
[1] Dana–Farber Cancer Institute,Department of Cancer Biology
[2] Harvard Medical School,Department of Biological Chemistry and Molecular Pharmacology
[3] Whitehead Institute for Biomedical Research,Department of Structural Immunology
[4] Structural Genomics Consortium,Department of Pharmacy
[5] University of Oxford,Department of Biochemistry
[6] Institute of Innate Immunity,Department of Biology
[7] University of Bonn,undefined
[8] Center of Advanced European Studies and Research,undefined
[9] Bonn,undefined
[10] Blais Proteomics Center,undefined
[11] Dana–Farber Cancer Institute,undefined
[12] Pharmaceutical and Medicinal Chemistry,undefined
[13] Saarland University,undefined
[14] Duke University Medical Center,undefined
[15] Massachusetts Institute of Technology,undefined
来源：
Nature Chemical Biology | 2016年 / 12卷
关键词：
D O I：
暂无
中图分类号：
学科分类号：
摘要：
A small molecule inhibits CDK12 and CDK13 activity through covalent modification of Cys residues and reveals a role of the two kinases in regulating Pol II processivity and super-enhancer-driven transcription factor and DNA damage response gene expression.[graphic not available: see fulltext]
引用
收藏
页码：876 / 884
页数：8
相关论文
共 50 条
  • [21] Dual inhibition of CDK12 and CDK13 uncovers actionable vulnerabilities in patient-derived ovarian cancer organoids
    Cesari, Eleonora
    Ciucci, Alessandra
    Pieraccioli, Marco
    Caggiano, Cinzia
    Nero, Camilla
    Bonvissuto, Davide
    Sillano, Francesca
    Buttarelli, Marianna
    Piermattei, Alessia
    Loverro, Matteo
    Camarda, Floriana
    Greco, Viviana
    De Bonis, Maria
    Minucci, Angelo
    Gallo, Daniela
    Urbani, Andrea
    Vizzielli, Giuseppe
    Scambia, Giovanni
    Sette, Claudio
    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2023, 42 (01)
  • [22] CDK12 loss drives prostate cancer progression, transcription-replication conflicts, and synthetic lethality with paralog CDK13
    Tien, Jean Ching-Yi
    Luo, Jie
    Chang, Yu
    Zhang, Yuping
    Cheng, Yunhui
    Wang, Xiaoju
    Yang, Jianzhang
    Mannan, Rahul
    Mahapatra, Somnath
    Shah, Palak
    Wang, Xiao-Ming
    Todd, Abigail J.
    Eyunni, Sanjana
    Cheng, Caleb
    Rebernick, Ryan J.
    Xiao, Lanbo
    Bao, Yi
    Neiswender, James
    Brough, Rachel
    Pettitt, Stephen J.
    Cao, Xuhong
    Miner, Stephanie J.
    Zhou, Licheng
    Wu, Yi-Mi
    Labanca, Estefania
    Wang, Yuzhuo
    Parolia, Abhijit
    Cieslik, Marcin
    Robinson, Dan R.
    Wang, Zhen
    Feng, Felix Y.
    Chou, Jonathan
    Lord, Christopher J.
    Ding, Ke
    Chinnaiyan, Arul M.
    CELL REPORTS MEDICINE, 2024, 5 (10)
  • [23] Targeting MYC dependency in ovarian cancer through inhibition of CDK7 and CDK12/13
    Zeng, Mei
    Kwiatkowski, Nicholas P.
    Zhang, Tinghu
    Nabet, Behnam
    Xu, Mousheng
    Liang, Yanke
    Quan, Chunshan
    Wang, Jinhua
    Hao, Mingfeng
    Palakurthi, Sangeetha
    Zhou, Shan
    Zeng, Qing
    Kirschmeier, Paul T.
    Meghani, Khyati
    Leggett, Alan L.
    Qi, Jun
    Shapiro, Geoffrey I.
    Liu, Joyce F.
    Matulonis, Ursula A.
    Lin, Charles Y.
    Konstantinopoulos, Panagiotis A.
    Gray, Nathanael S.
    ELIFE, 2018, 7
  • [24] Potent selective and orally bioavailable inhibition of CDK12 by novel covalent inhibitors
    Poddutoori, Ramulu
    Rajagopalan, Sujatha
    Mukherjee, Subhendu
    Marappan, Sivapriya
    Samiulla, D. S.
    Kasturi, Venkateswarlu
    Sivakumar, Sasirekha
    Nayak, Shilpa
    Ravindra, M., V
    Tgore, Suraj
    Dhudashiya, Amit
    Charamanna, K. B.
    Antony, Thomas
    Mahaboobi, M.
    Giri, Sanjeev
    Daginakatte, Girish C.
    Chelur, Shekar
    Ramachandra, Murali
    Pandit, Chetan
    Samajdar, Susanta
    MOLECULAR CANCER THERAPEUTICS, 2018, 17 (01)
  • [25] A patent and literature review of CDK12 inhibitors
    Tang, Ruijun
    Liu, Jing
    Li, Shuyao
    Zhang, Junjie
    Yu, Chunhong
    Liu, Honglu
    Chen, Fang
    Lv, Lu
    Zhang, Qian
    Yuan, Kai
    Shao, Hao
    EXPERT OPINION ON THERAPEUTIC PATENTS, 2022, 32 (10) : 1055 - 1065
  • [26] CDK12/13 dual inhibitors are potential therapeutics for acute myeloid leukemia
    Savoy, Lindsey
    Long, Nicola
    Lee, Hyunjung
    Chen, Reid
    Allen, Basil
    Lin, Hsin-Yun
    Tognon, Cristina
    Malhotra, Sanjay
    Tyner, Jeffrey W.
    Zhang, Haijiao
    BRITISH JOURNAL OF HAEMATOLOGY, 2023, 202 (01) : 195 - 198
  • [27] MYC up-regulation confers vulnerability to dual inhibition of CDK12 and CDK13 in high-risk Group 3 medulloblastoma
    Pitolli, Consuelo
    Marini, Alberto
    Guerra, Marika
    Pieraccioli, Marco
    Marabitti, Veronica
    Palluzzi, Fernando
    Giaco, Luciano
    Tamburrini, Gianpiero
    Cecconi, Francesco
    Nazio, Francesca
    Sette, Claudio
    Pagliarini, Vittoria
    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2023, 42 (01)
  • [28] MYC up-regulation confers vulnerability to dual inhibition of CDK12 and CDK13 in high-risk Group 3 medulloblastoma
    Consuelo Pitolli
    Alberto Marini
    Marika Guerra
    Marco Pieraccioli
    Veronica Marabitti
    Fernando Palluzzi
    Luciano Giacò
    Gianpiero Tamburrini
    Francesco Cecconi
    Francesca Nazio
    Claudio Sette
    Vittoria Pagliarini
    Journal of Experimental & Clinical Cancer Research, 42
  • [29] Research progress of anticancer drugs targeting CDK12
    Yan, Zhijia
    Du, Yongli
    Zhang, Haibin
    Zheng, Yong
    Lv, Huiting
    Dong, Ning
    He, Fang
    RSC MEDICINAL CHEMISTRY, 2023, 14 (09): : 1629 - 1644
  • [30] Targeting CDK12 to treat DM1
    Sarah Crunkhorn
    Nature Reviews Drug Discovery, 2020, 19 (6) : 388 - 388
12345