CDK7 Inhibitors in Cancer Therapy: The Sweet Smell of Success?

Journal of Medicinal Chemistry
Sarah DiabShudong Wang

Abstract

Cyclin-dependent kinase (CDK) 7 has a unique functional repertoire by virtue of its dual role in transcription and cell cycle progression. Whereas CDK7 is ubiquitously expressed in various types of cancer, its downregulation leads to reduced cell proliferation. Importantly, it is now agreed that targeting transcription selectively limits the synthesis of mRNAs involved in tumor growth without causing an outage of transcription of housekeeping genes. Thus, CDK7 has been considered as a viable therapeutic target in cancer. Indeed, the development of CDK7 inhibitors has gained huge momentum with two molecules, CT7001 and SY-1365, currently under clinical development. Herein, we discuss the latest understanding of the role of CDK7 in cancer cells and provide an overview of the pharmacophores of CDK7 inhibitors, their efficacy in various cancer models, and their clinical development.

References

Mar 6, 1998·Molecular and Cellular Biology·J J LongJ M Gottesfeld
Nov 9, 2004·Structure·Graziano LolliLouise N Johnson
Mar 30, 2007·Proceedings of the National Academy of Sciences of the United States of America·Elenita I KaninAseem Z Ansari
May 5, 2010·Proceedings of the National Academy of Sciences of the United States of America·Brion W MurrayTod Smeal
May 11, 2012·Current Pharmaceutical Design·Radek JordaVladimír Krystof
Oct 16, 2012·Nature Structural & Molecular Biology·Stéphane LarochelleRobert P Fisher
Apr 30, 2013·Molecular Cell·Miriam Merzel SchachterRobert P Fisher
Sep 17, 2013·Cell Cycle·Miriam Merzel Schachter, Robert P Fisher
Jul 22, 2014·Nature·Nicholas KwiatkowskiNathanael S Gray
Nov 22, 2014·Journal of Medicinal Chemistry·Joachim RudolphWeiru Wang
Jan 28, 2015·Antimicrobial Agents and Chemotherapy·Corina HuttererManfred Marschall
Jan 31, 2015·Nature Reviews. Drug Discovery·Uzma AsgharErik S Knudsen
Mar 31, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jianguo ZhangYe Tian
Aug 11, 2015·Molecular Cell·Kyle A NilsonDavid H Price
Apr 16, 2016·F1000Research·Valeriya Posternak, Michael D Cole
May 8, 2016·Experimental and Molecular Pathology·Qiuhong WangLei Yang
Nov 4, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hetal PatelSimak Ali
Aug 30, 2016·Nature Chemical Biology·Tinghu ZhangNathanael S Gray
Oct 25, 2016·Future Medicinal Chemistry·Tinghan LiZhiyu Li
Jan 28, 2017·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Michaela NekardováKamil Paruch
Feb 9, 2017·Pharmacology & Therapeutics·Steven R WhittakerPaul A Clarke
May 16, 2017·Oncogenesis·S A GreenallT G Johns
Oct 22, 2017·Cancer Discovery·Maria RusanPeter S Hammerman
Dec 26, 2017·Cell Chemical Biology·Yang GaoRani E George
Feb 7, 2018·The Journal of Investigative Dermatology·Philip EliadesHensin Tsao
Mar 17, 2018·Molecular Cancer Therapeutics·Hetal PatelSimak Ali

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Citations

Dec 2, 2020·European Journal of Medicinal Chemistry·Dan WuXinhua Liu
Feb 24, 2021·Trends in Microbiology·Lucia Gutierrez-ChamorroEster Ballana
Jun 3, 2021·Cancers·Ranadip MandalKlaus Strebhardt
Jun 10, 2021·Therapeutic Advances in Musculoskeletal Disease·Hangzhan MaZhenfeng Duan
Nov 3, 2021·Journal of Medicinal Chemistry·Jason J MarineauClaudio Chuaqui

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