An oncoinformatics study to predict the inhibitory potential of recent FDA-approved anti-cancer drugs against human Polo-like kinase 1 enzyme: a step towards dual-target cancer medication

3 Biotech
Syed Mohd Danish RizviRakan F Alshammari

Abstract

Cancer prevalence has increased at an alarming rate worldwide. Complexity, resistance mechanism and multiple compensatory survival pathways of cancer cells have abated the response of currently available cancer medications. Therefore, multi-target agents rather than single target might provide a better solution to these cancer therapy issues. In the present study, anti-PLK1 (Polo-like kinase 1) potential of the eight FDA-approved (2017) anti-cancer drugs have been explored using molecular docking approach. Out of all the tested drugs, brigatinib, niraparib and ribociclib showed better binding affinity towards the 'kinase domain' of PLK1. The Gibbs free binding energy (ΔG) and inhibition constant (Ki) values for brigatinib, niraparib and ribociclib interaction with the kinase domain of PLK1 were '- 8.05 kcal/mol and 1.26 µM', '- 8.35 kcal/mol and 0.729 µM' and '- 7.29 kcal/mol and 4.52 µM', respectively. Interestingly, the docking results of these three drugs were better than the known PLK1 inhibitors (BI-2536 and rigosertib). The ΔG and Ki values for BI-2536 and rigosertib interaction with the kinase domain of PLK1 were '- 6.8 kcal/mol and 10.38 µM' and '- 6.6 kcal/mol and 14.51 µM', respectively. Brigatinib, niraparib and ribo...Continue Reading

References

Aug 1, 1980·Cancer Nursing·B A SatterwhiteM B Harris
Dec 31, 1998·Genes & Development·D M GloverA A Tavares
Apr 5, 2002·Molecular Cell·Izabela SumaraJan-Michael Peters
Jul 24, 2002·Journal of Cutaneous Pathology·Lucas KneiselRoland Kaufmann
Apr 24, 2003·Cancer Science·Takao TakahashiShigetoyo Saji
Mar 16, 2005·Cancer Cell·Kiranmai GumireddyE Premkumar Reddy
Mar 24, 2005·Virchows Archiv : an International Journal of Pathology·Wilko WeichertCarsten Denkert
Mar 2, 2006·Molecular and Cellular Biology·Xiaoqi LiuRaymond L Erikson
Mar 25, 2006·Nature Reviews. Cancer·Klaus Strebhardt, Axel Ullrich
Apr 22, 2006·Cell Cycle·Barbara C M van de Weerdt, René H Medema
Feb 13, 2007·Current Biology : CB·Martin SteegmaierWolfgang J Rettig
Nov 26, 2010·Nature Reviews. Cancer·Susanne M A LensRené H Medema
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
Jan 25, 2012·International Journal of Molecular Sciences·Shuai LuTao Lu
Mar 17, 2012·Mini Reviews in Medicinal Chemistry·A TaleviE A Castro
Sep 26, 2013·Nature Reviews. Cancer·Caitriona HolohanPatrick G Johnston
Jan 28, 2014·Pharmaceuticals·Hailin ZhengMoussa Youdim
Feb 27, 2014·Journal of Medicinal Chemistry·Kai LiEric Oldfield
Aug 31, 2014·Drug Discovery Today·Andreas Koeberle, Oliver Werz
Nov 29, 2015·BioMedicine·Viswanadha Vijaya Padma
Jan 29, 2016·International Journal of Molecular Sciences·Xing DuShu-Qun Liu
Oct 9, 2016·The New England Journal of Medicine·Mansoor R MirzaUNKNOWN ENGOT-OV16/NOVA Investigators
Nov 27, 2016·Translational Oncology·Zhixian LiuXiaosheng Wang
May 27, 2017·Blood·Mark Levis
Jun 8, 2017·Blood·Eytan M SteinMartin S Tallman
Jun 22, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M DreylingP L Zinzani
Jun 27, 2017·Expert Review of Anticancer Therapy·Isabel EchavarriaMiguel Martin
Oct 3, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Matthew P GoetzAngelo Di Leo
Nov 11, 2017·Seminars in Cancer Biology·Shazi ShakilAdeel G Chaudhary
Feb 14, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anand ShahRichard Pazdur
Mar 10, 2018·Expert Opinion on Pharmacotherapy·Takeshi Kotake, Masakazu Toi
May 18, 2018·Expert Review of Clinical Pharmacology·James Dugan, Daniel Pollyea
Jun 19, 2018·Expert Review of Anticancer Therapy·Kathleen G Essel, Kathleen N Moore
Sep 12, 2018·Saudi Pharmaceutical Journal : SPJ : the Official Publication of the Saudi Pharmaceutical Society·Silky BediAsif Husain

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