Literature DB >> 24517277

Therapeutic melting pot of never in mitosis gene a related kinase 2 (Nek2): a perspective on Nek2 as an oncology target and recent advancements in Nek2 small molecule inhibition.

Brendan Frett1, Robert V Brown, Mingliang Ma, Wenhao Hu, Haiyong Han, Hong-yu Li.   

Abstract

The global incidence of cancer is on the rise, and within the next decade, the disease is expected to become the leading cause of death worldwide. Forthcoming strategies used to treat cancers focus on the design and implementation of multidrug therapies to target complementary cancer specific pathways. A more direct means by which this multitargeted approach can be achieved is by identifying and targeting interpathway regulatory factors. Recent advances in understanding Nek2 (NIMA related kinase 2) biology suggest that the kinase potentially represents a multifaceted therapeutic target. In this regard, pharmacologic modulation of Nek2 with a single agent may effect several mechanisms important for tumor growth, survival, progression, and metastasis. We herein review the development of Nek2 as an oncology target and provide a succinct chronology of drug discovery campaigns focused on targeting Nek2.

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Year:  2014        PMID: 24517277      PMCID: PMC4666018          DOI: 10.1021/jm401719n

Source DB:  PubMed          Journal:  J Med Chem        ISSN: 0022-2623            Impact factor:   7.446


  55 in total

1.  Phase I study of GSK461364, a specific and competitive Polo-like kinase 1 inhibitor, in patients with advanced solid malignancies.

Authors:  David Olmos; Douglas Barker; Rohini Sharma; Andre T Brunetto; Timothy A Yap; Anne B Taegtmeyer; Jorge Barriuso; Hanine Medani; Yan Y Degenhardt; Alicia J Allred; Deborah A Smith; Sharon C Murray; Thomas A Lampkin; Mohammed M Dar; Richard Wilson; Johann S de Bono; Sarah P Blagden
Journal:  Clin Cancer Res       Date:  2011-04-01       Impact factor: 12.531

2.  Gene expression profile of serial samples of transformed B-cell lymphomas.

Authors:  Sven de Vos; Wolf-Karsten Hofmann; Thomas M Grogan; Utz Krug; Mathew Schrage; Thomas P Miller; Jonathan G Braun; William Wachsman; H Phillip Koeffler; Jonathan W Said
Journal:  Lab Invest       Date:  2003-02       Impact factor: 5.662

3.  Irreversible Nek2 kinase inhibitors with cellular activity.

Authors:  Jeffrey C Henise; Jack Taunton
Journal:  J Med Chem       Date:  2011-05-31       Impact factor: 7.446

4.  RNA expression of breast cancer resistance protein, lung resistance-related protein, multidrug resistance-associated proteins 1 and 2, and multidrug resistance gene 1 in breast cancer: correlation with chemotherapeutic response.

Authors:  Herman Burger; John A Foekens; Maxime P Look; Marion E Meijer-van Gelder; Jan G M Klijn; Erik A C Wiemer; Gerrit Stoter; Kees Nooter
Journal:  Clin Cancer Res       Date:  2003-02       Impact factor: 12.531

5.  An essential role for the Plasmodium Nek-2 Nima-related protein kinase in the sexual development of malaria parasites.

Authors:  Luc Reininger; Rita Tewari; Clare Fennell; Zoe Holland; Dean Goldring; Lisa Ranford-Cartwright; Oliver Billker; Christian Doerig
Journal:  J Biol Chem       Date:  2009-06-02       Impact factor: 5.157

6.  Protein phosphatase-1alpha regulates centrosome splitting through Nek2.

Authors:  Jun Mi; Changyue Guo; David L Brautigan; James M Larner
Journal:  Cancer Res       Date:  2007-02-01       Impact factor: 12.701

7.  Detection of P-glycoprotein in ovarian cancer: a molecular marker associated with multidrug resistance.

Authors:  D R Bell; J H Gerlach; N Kartner; R N Buick; V Ling
Journal:  J Clin Oncol       Date:  1985-03       Impact factor: 44.544

8.  Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer.

Authors:  John V Heymach; Luis Paz-Ares; Filippo De Braud; Martin Sebastian; David J Stewart; Wilfried E E Eberhardt; Anantbhushan A Ranade; Graham Cohen; Jose Manuel Trigo; Alan B Sandler; Philip D Bonomi; Roy S Herbst; Annetta D Krebs; James Vasselli; Bruce E Johnson
Journal:  J Clin Oncol       Date:  2008-10-20       Impact factor: 44.544

Review 9.  Cell cycle regulation by the NEK family of protein kinases.

Authors:  Andrew M Fry; Laura O'Regan; Sarah R Sabir; Richard Bayliss
Journal:  J Cell Sci       Date:  2012-11-06       Impact factor: 5.285

Review 10.  New antimetabolites in cancer chemotherapy and their clinical impact.

Authors:  S B Kaye
Journal:  Br J Cancer       Date:  1998       Impact factor: 7.640

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  9 in total

Review 1.  Cilium assembly and disassembly.

Authors:  Irma Sánchez; Brian David Dynlacht
Journal:  Nat Cell Biol       Date:  2016-06-28       Impact factor: 28.824

2.  Nek2 activation of Kif24 ensures cilium disassembly during the cell cycle.

Authors:  Sehyun Kim; Kwanwoo Lee; Jung-Hwan Choi; Niels Ringstad; Brian David Dynlacht
Journal:  Nat Commun       Date:  2015-08-20       Impact factor: 14.919

3.  Molecular modeling and docking of small molecule inhibitors against NEK2.

Authors:  Balaji Ramachandran; Sabitha Kesavan; Thangarajan Rajkumar
Journal:  Bioinformation       Date:  2016-04-10

4.  Modelling of the cancer cell cycle as a tool for rational drug development: A systems pharmacology approach to cyclotherapy.

Authors:  Robert C Jackson; Giovanni Y Di Veroli; Siang-Boon Koh; Ian Goldlust; Frances M Richards; Duncan I Jodrell
Journal:  PLoS Comput Biol       Date:  2017-05-03       Impact factor: 4.475

Review 5.  Maintenance of genome stability by Fanconi anemia proteins.

Authors:  Anna Palovcak; Wenjun Liu; Fenghua Yuan; Yanbin Zhang
Journal:  Cell Biosci       Date:  2017-02-22       Impact factor: 7.133

6.  CGK062, a small chemical molecule, inhibits cancer upregulated gene 2‑induced oncogenesis through NEK2 and β‑catenin.

Authors:  Sirichat Kaowinn; Sangtaek Oh; Jeong Moon; Ah Young Yoo; Ho Young Kang; Mi Rim Lee; Ji Eun Kim; Dae Youn Hwang; So Eun Youn; Sang Seok Koh; Young-Hwa Chung
Journal:  Int J Oncol       Date:  2019-02-22       Impact factor: 5.650

7.  NEK2 Serves as a Novel Biomarker and Enhances the Tumorigenicity of Clear-CellRenal-Cell Carcinoma by Activating WNT/β-Catenin Pathway.

Authors:  Jiancheng Zhou; Jiawei Lai; Yongyi Cheng; Weixing Qu
Journal:  Evid Based Complement Alternat Med       Date:  2022-09-29       Impact factor: 2.650

Review 8.  Functional aspects of primary cilium in signaling, assembly and microenvironment in cancer.

Authors:  Bo Wang; Zheyong Liang; Peijun Liu
Journal:  J Cell Physiol       Date:  2020-10-26       Impact factor: 6.384

Review 9.  Nek2 Kinase Signaling in Malaria, Bone, Immune and Kidney Disorders to Metastatic Cancers and Drug Resistance: Progress on Nek2 Inhibitor Development.

Authors:  Dibyendu Dana; Tuhin Das; Athena Choi; Ashif I Bhuiyan; Tirtha K Das; Tanaji T Talele; Sanjai K Pathak
Journal:  Molecules       Date:  2022-01-06       Impact factor: 4.927

  9 in total

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