Literature DB >> 26766294

Overview of CDK9 as a target in cancer research.

Fatima Morales1, Antonio Giordano1,2.   

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.

Entities:  

Keywords:  CDK9; anticancer; antitumor; cyclin; drug development; kinase; molecular modeling

Mesh:

Substances:

Year:  2016        PMID: 26766294      PMCID: PMC5056610          DOI: 10.1080/15384101.2016.1138186

Source DB:  PubMed          Journal:  Cell Cycle        ISSN: 1551-4005            Impact factor:   4.534


  93 in total

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Journal:  J Biol Chem       Date:  1996-08-09       Impact factor: 5.157

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5.  Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor.

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Journal:  J Mol Biol       Date:  2012-12-13       Impact factor: 5.469

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Journal:  Blood       Date:  2014-11-13       Impact factor: 25.476

Review 10.  Perspective of cyclin-dependent kinase 9 (CDK9) as a drug target.

Authors:  Vladimír Krystof; Sonja Baumli; Robert Fürst
Journal:  Curr Pharm Des       Date:  2012       Impact factor: 3.116

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  71 in total

Review 1.  Drug development against the hippo pathway in mesothelioma.

Authors:  Gavitt A Woodard; Yi-Lin Yang; Liang You; David M Jablons
Journal:  Transl Lung Cancer Res       Date:  2017-06

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Authors:  Muhammed H Rahaman; Yingyi Yu; Longjin Zhong; Julian Adams; Frankie Lam; Peng Li; Ben Noll; Robert Milne; Jun Peng; Shudong Wang
Journal:  Invest New Drugs       Date:  2018-09-08       Impact factor: 3.850

Review 3.  ENL: structure, function, and roles in hematopoiesis and acute myeloid leukemia.

Authors:  Jianbiao Zhou; Yvonne Ng; Wee-Joo Chng
Journal:  Cell Mol Life Sci       Date:  2018-07-31       Impact factor: 9.261

4.  Inhibition of CDK9 by voruciclib synergistically enhances cell death induced by the Bcl-2 selective inhibitor venetoclax in preclinical models of acute myeloid leukemia.

Authors:  Daniel A Luedtke; Yongwei Su; Jun Ma; Xinyu Li; Steven A Buck; Holly Edwards; Lisa Polin; Juiwanna Kushner; Sijana H Dzinic; Kathryn White; Hai Lin; Jeffrey W Taub; Yubin Ge
Journal:  Signal Transduct Target Ther       Date:  2020-02-26

Review 5.  Kinase inhibitors: the road ahead.

Authors:  Fleur M Ferguson; Nathanael S Gray
Journal:  Nat Rev Drug Discov       Date:  2018-03-16       Impact factor: 84.694

6.  Chromatin modifiers Mdm2 and RNF2 prevent RNA:DNA hybrids that impair DNA replication.

Authors:  Ina Klusmann; Kai Wohlberedt; Anna Magerhans; Federico Teloni; Jan O Korbel; Matthias Altmeyer; Matthias Dobbelstein
Journal:  Proc Natl Acad Sci U S A       Date:  2018-11-09       Impact factor: 11.205

7.  In Vitro and In Vivo Antitumor and Anti-Inflammatory Capabilities of the Novel GSK3 and CDK9 Inhibitor ABC1183.

Authors:  Randy S Schrecengost; Cecelia L Green; Yan Zhuang; Staci N Keller; Ryan A Smith; Lynn W Maines; Charles D Smith
Journal:  J Pharmacol Exp Ther       Date:  2018-02-06       Impact factor: 4.030

8.  TEA Domain Transcription Factor 4 Is the Major Mediator of Yes-Associated Protein Oncogenic Activity in Mouse and Human Hepatoblastoma.

Authors:  Jie Zhang; Pin Liu; Junyan Tao; Pan Wang; Yi Zhang; Xinhua Song; Li Che; Pavel Sumazin; Silvia Ribback; Andras Kiss; Zsuzsa Schaff; Antonio Cigliano; Frank Dombrowski; Carla Cossu; Rosa M Pascale; Diego F Calvisi; Satdarshan P Monga; Xin Chen
Journal:  Am J Pathol       Date:  2019-02-19       Impact factor: 4.307

9.  CSB-Dependent Cyclin-Dependent Kinase 9 Degradation and RNA Polymerase II Phosphorylation during Transcription-Coupled Repair.

Authors:  Lise-Marie Donnio; Anna Lagarou; Gabrielle Sueur; Pierre-Olivier Mari; Giuseppina Giglia-Mari
Journal:  Mol Cell Biol       Date:  2019-03-01       Impact factor: 4.272

10.  A Precision Medicine Drug Discovery Pipeline Identifies Combined CDK2 and 9 Inhibition as a Novel Therapeutic Strategy in Colorectal Cancer.

Authors:  Jason A Somarelli; Roham Salman Roghani; Ali Sanjari Moghaddam; Beatrice C Thomas; Gabrielle Rupprecht; Kathryn E Ware; Erdem Altunel; John B Mantyh; So Young Kim; Shannon J McCall; Xiling Shen; Christopher R Mantyh; David S Hsu
Journal:  Mol Cancer Ther       Date:  2020-11-06       Impact factor: 6.261

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