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Updated: Apr 23, 2026
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
Virtual screening and discovery of novel aurora kinase inhibitors
R Raghu, Vinod Devaraji, K Leena
1Department of Bioinformatics and Biotechnology, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, India-173 215. rraghu1@yahoo.com.
Abstract:
Cancer remains one of the major contributors to human mortality and a hazard to human growth. The search for a new treatment continues unabated. Aurora kinases play an important role in cell cycle, and thus a potential target for the treatment of cancer. In the present work, we aim to discover potential leads against aurora kinase using various rational methods of drug discovery. The available crystal complexes of AKs were analyzed for their interactions and quantified with glide-extra precision (XP) docking. About 20 crystal pdb were selected from the protein databank based on the resolution factor, R-factor and R-value. And after docking with the native ligands, the RMSD value was calculated, wherein the protein with the least RMSD was found to be 3UOK which was further used for our screening of small molecules from the in-house database by molecular docking. Fragments which were found to possess the best interactions were considered for the synthesis with characterization, and biological activity was carried out against breast cancer and colorectal cancer cell lines to assess the inhibitory capability of synthesized compounds. Molecule with the molecular id IS2 i.e. (3E)-3-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2H chromene-2,4(3H)-dione was found to possess inhibitory activity with an IC50 of 1.324 nM and 5.785 µM for breast cell line and colorectal cell line studies, respectively.
Insights
Researchers identified a novel compound, IS2, demonstrating potent inhibitory activity against aurora kinases, a key target in cancer treatment. This discovery offers a promising new avenue for developing effective cancer therapies targeting cell cycle regulation.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Oncology
Background:
- Aurora kinases (AKs) are crucial regulators of cell division and represent promising therapeutic targets for cancer treatment.
- Despite their importance, developing effective AK inhibitors remains a challenge in oncology drug discovery.
Purpose of the Study:
- To discover novel small molecules with potent inhibitory activity against aurora kinases using rational drug design methods.
- To identify potential lead compounds for the development of new anti-cancer therapeutics.
Main Methods:
- Utilized molecular docking (glide-extra precision) on selected aurora kinase crystal structures (PDB) to screen an in-house database of small molecules.
- Validated protein targets by calculating RMSD values after docking native ligands, selecting 3UOK as the most suitable target.
- Synthesized promising compounds based on docking interactions and evaluated their biological activity against breast and colorectal cancer cell lines.
Main Results:
- Identified a specific molecule, IS2 ((3E)-3-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2H chromene-2,4(3H)-dione), exhibiting significant inhibitory potential.
- IS2 demonstrated potent inhibitory activity with an IC50 of 1.324 nM against breast cancer cell lines.
- IS2 also showed inhibitory activity against colorectal cancer cell lines with an IC50 of 5.785 µM.
Conclusions:
- The identified compound IS2 shows significant promise as a potential therapeutic agent for breast and colorectal cancers.
- This study highlights the efficacy of rational drug design and molecular docking in identifying novel kinase inhibitors for cancer therapy.
