Overview of CDK9 as a target in cancer research

Cell Cycle
Fatima Morales, Antonio Giordano

Abstract

CDK9 is a protein in constant development in cancer therapy. Herein we present an overview of the enzyme as a target for cancer therapy. We provide data on its characteristics and mechanism of action. In recent years, CDK9 inhibitors that have been designed with molecular modeling have demonstrated good antitumoral activity in vitro. Clinical studies of the drugs flavopiridol, dinaciclib, seliciclib, SNS-032 and RGB-286638 used as CDK9 inhibitors are also reviewed, with their additional targets and their relative IC50 values. Unfortunately, treatment with these drugs remains unsuccessful and involves many adverse effects. We could conclude that there are many small molecules that bind to CDK9, but their lack of selectivity against other CDKs do not allow them to get to the clinical use. However, drug designers currently have the tools needed to improve the selectivity of CDK9 inhibitors and to make successful treatment available to patients.

References

Oct 1, 1990·Trends in Biochemical Sciences·J L Corden
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·X GrañaA Giordano
Aug 9, 1996·The Journal of Biological Chemistry·M E Dahmus
Dec 15, 1996·The Biochemical Journal·J GarrigaX Graña
Apr 16, 1998·Genes & Development·J PengD H Price
Apr 18, 1998·The Journal of Biological Chemistry·S TrigonM Morange
Jun 5, 1998·The Journal of Biological Chemistry·J PengD H Price
Mar 6, 1999·The Journal of Biological Chemistry·Y H Ping, T M Rana
Mar 26, 1999·Journal of Cellular Physiology·G de Falco, A Giordano
Mar 25, 2000·Molecular and Cellular Biology·D H Price
Jan 17, 2002·Leukemia Research·Igor SemenovSeth J Corey
Jan 25, 2002·Journal of Cellular Physiology·Thomas Oelgeschläger
Jun 11, 2002·Biochemical and Biophysical Research Communications·Walter Filgueira de AzevedoNelson José Freitas da Silveira
Nov 15, 2002·Cancer Biology & Therapy·Giulia De Falco, Antonio Giordano
Apr 23, 2003·Gene·Sarah M ShoreDavid H Price
Oct 1, 2003·The EMBO Journal·Charalambos SpilianakisJoseph Papamatheakis
Sep 29, 2004·Journal of Cellular Physiology·Hongbing Liu, Christine H Herrmann
Nov 15, 2007·Pediatric Blood & Cancer·Kelly M JackmanStephen P Hunger
Nov 4, 2009·American Journal of Clinical Oncology·Houman M FekrazadIan Rabinowitz
May 13, 2010·Investigational New Drugs·Mark Andrew DicksonGary K Schwartz
May 19, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Wei-Gang TongWilliam G Wierda
May 25, 2010·Biochemical and Biophysical Research Communications·Hongbing LiuAndrew P Rice
Jul 29, 2010·Molecular Cancer Therapeutics·David ParryEmma M Lees
Sep 9, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Christophe Le TourneauEric Raymond
Sep 21, 2010·Chemistry & Biology·Sonja BaumliLouise N Johnson
Oct 19, 2010·Cancer Chemotherapy and Pharmacology·Mark A DicksonGary K Schwartz
Jul 23, 2011·European Journal of Medicinal Chemistry·Vladimír KryštofPetr Cankař
Oct 11, 2011·Bioorganic & Medicinal Chemistry·Stuart C WilsonEdward McDonald

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Citations

Oct 31, 2016·Journal of Cellular Physiology·Annamaria CiminiAntonio Giordano
Jul 14, 2017·Artificial Cells, Nanomedicine, and Biotechnology·Yebin LuWei Wei
Mar 17, 2018·Nature Reviews. Drug Discovery·Fleur M Ferguson, Nathanael S Gray
Jul 20, 2017·Journal of Cellular Biochemistry·Lia Carolina FrancoAntonio Giordano
Aug 2, 2018·Cellular and Molecular Life Sciences : CMLS·Jianbiao ZhouWee-Joo Chng
Sep 20, 2018·Médecine sciences : M/S·Alessandro FurlanLaurent Héliot
Nov 30, 2018·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Xiaoyang LiZhenfeng Duan
Feb 24, 2018·Journal of Experimental & Clinical Cancer Research : CR·Silvia BoffoAntonio Giordano
Jan 4, 2019·Molecular and Cellular Biology·Lise-Marie DonnioGiuseppina Giglia-Mari
Oct 27, 2018·Current Drug Targets·Shirin EyvaziVahideh Tarhriz
Sep 9, 2018·Investigational New Drugs·Muhammed H RahamanShudong Wang
Feb 13, 2018·The Journal of Pharmacology and Experimental Therapeutics·Randy S SchrecengostCharles D Smith
Aug 10, 2019·Molecular Oncology·Muhammed H RahamanShudong Wang
Feb 7, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jinglu WangZhenfeng Duan
Jun 20, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Shuyan LuWenyue Hu
Apr 11, 2018·FEBS Open Bio·Hidetaka SadanariTsugiya Murayama
Nov 11, 2018·Proceedings of the National Academy of Sciences of the United States of America·Ina KlusmannMatthias Dobbelstein
Jan 11, 2020·Frontiers in Oncology·Raoul Tibes, James M Bogenberger
Aug 7, 2019·Therapeutic Advances in Medical Oncology·Zhimin TongDipen M Maru
Aug 14, 2019·Frontiers in Immunology·Elijah W ChenVasily Rybakin
Dec 4, 2019·Nature Reviews. Clinical Oncology·Joseph A ClaraNaoko Takebe
Feb 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Koh Fujinaga
Oct 20, 2019·Nature Communications·Ingeborg MenzlVeronika Sexl
Jul 22, 2020·European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society·Pichaya ThanindratarnZhenfeng Duan
Jan 5, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Xin WangRong Xiang
Jul 18, 2020·Cell Death & Disease·Josephine Ann Mun Yee ChooMatthias Dobbelstein
Nov 9, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Justin CidadoLisa Drew
Dec 18, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Clara AlconJoan Montero
Aug 25, 2019·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Daisy W S MakAnna Minchom
Jan 21, 2021·Cancers·Renya Zeng, Jixin Dong

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