3 Biotech

, 9:70 | Cite as

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

  • Syed Mohd. Danish RizviEmail author
  • Abdulaziz Arif A. Alshammari
  • Waleed Abdullah Almawkaa
  • Abo Bakr F. Ahmed
  • Ahmed Katamesh
  • Ahmed Alafnan
  • Tariq J. Almutairi
  • Rakan F. Alshammari
Original Article


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 ribociclib have been approved by FDA for the treatment of non-small cell lung cancer, ovarian/fallopian tube cancer and breast cancer, respectively. PLK1 is regarded as a potential cancer target, and it is specifically over-expressed in different types of cancer cells, including aforementioned cancers. Actually, the target enzymes for anti-cancer action of brigatinib, niraparib and ribociclib are tyrosine kinase, poly(ADP-ribose) polymerase and cyclin-dependent kinase 4/6, respectively. However, based on our outcomes, we could safely state that PLK1 might plausibly emerge as an add-on target for each of these three anti-cancer drugs. We strongly believe that this study would assist in the development of better dual-targeting cancer therapeutic agent in the near future.


Anticancer drugs Dual therapy Molecular docking Multi-target agents Polo-like kinase 1 


Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.


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Copyright information

© King Abdulaziz City for Science and Technology 2019

Authors and Affiliations

  • Syed Mohd. Danish Rizvi
    • 1
    Email author
  • Abdulaziz Arif A. Alshammari
    • 2
  • Waleed Abdullah Almawkaa
    • 2
  • Abo Bakr F. Ahmed
    • 3
  • Ahmed Katamesh
    • 3
  • Ahmed Alafnan
    • 1
  • Tariq J. Almutairi
    • 2
  • Rakan F. Alshammari
    • 2
  1. 1.Department of Pharmacology and Toxicology, College of PharmacyUniversity of HailHailSaudi Arabia
  2. 2.College of PharmacyUniversity of HailHailSaudi Arabia
  3. 3.Department of Pharmaceutics, College of PharmacyUniversity of HailHailSaudi Arabia

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