3D-Pharmacophore Modeling, Molecular Docking, and Virtual Screening for Discovery of Novel CDK4/6 Selective Inhibitors

Structure-based pharmacophore mapping, drug-likeness and ADMET profiles were used as tools in our virtual screening process, in addition to molecular docking studies that were used to find novel CDK4/6 inhibitors with different heterocyclic scaffolds, having appropriate physicochemical parameters and non toxic. Aim of this work is to search for new promising CDK4/6 inhibitors, that have a great potential to be approved as clinically useful drugs in cancer therapy. Six promising hits were retrieved after applying virtual screening filters, these hits were subjected to molecular docking studies and were compared with the approved CDK4/6 inhibitor drug (palbociclib). Finally, we can conclude that they have a great potential to target CDK4/6 in a closely similar manner as palbociclib, in addition to their predicted good ADMET properties, they can be considered as novel hopeful leads for CDK4/6 inhibition and deserve further clinical investigations.

Automated summary

Structure-based pharmacophore mapping, drug-likeness, and ADMET profiles were utilized in virtual screening to identify potential CDK4/6 inhibitors, along with molecular docking studies for novel compounds with different scaffolds. The six promising hits showed potential for CDK4/6 inhibition and further clinical investigations, with similarities to the approved drug palbociclib and favorable ADMET properties.