Ligand- and structure-based pharmacophore modeling, docking study reveals 2-[[4-[6-(isopropylamino) pyrimidin-4-yl]-1H-pyrrolo[2,3-b] pyridin-6-yl] amino] ethanol as a potential anticancer agent of CDK9/cyclin T1 kinase

Objective: CDK9/Cyclin T1 kinase is a protein kinase, indirectly involved in the cell cycle progression in the form of transcription elongation, CDK9 specific inhibitors may be a potential alternative treatment not only for cancer but also other life-threatening diseases.

Materials and methods: Ligand-based and structure-based pharmacophore model was developed for discovering of the new anticancer agents. These models used as three-dimensional query for virtual screening against the chemical structure databases such as Maybridge HitFinder, MDPI, and ZINC. Subsequently, the potential hit compound was filtered by the ADMET and docking score.

Results: After applying all filtration, 11 hits were found as potential hits based on good docking scores as well as good ADMET properties. Compound 2-[4-[6-(isopropylamino) pyrimidin-4-yl]-1H-pyrrolo[2,3-b] pyridin-6-yl] amino] ethanol was found to be most potent among all the potential hits. These hits could be used as an anticancer agent in near future.

Conclusions: So many advances in the treatment of death leading diseases have been made over the past few decades, However, looking for the development in this research ligand-based and structure-based pharmacophore modeling was done, hit1 2-[4-[6-(isopropylamino) pyrimidin-4-yl]-1H-pyrrolo[2,3 b] pyridin-6 yl] amino] ethanol was found to be more potent and selective. It is understandable that these hits could be as selective and potent anticancer agents of cyclin-dependent kinase complex.