S.Prasanth Kumar
NOTE: THIS ARTICLE HAS BEEN ACCEPTED BY JCIB. FULL MANUCRIPT IS COPYRIGHTED BY JCIB.
ABSTRACT
Acute lymphoblastic leukemia can be controlled by inhibition of the cyclin-dependent kinase 6 –Retinoblastoma (CDK6-Rb) pathway. In this study, CDK6, a key regulator that allows progression through G1 and then G1/S transition of cell cycle, was used as target. Docking studies using ArgusLab with known flavonol CDK6 inhibitors and computationally designed analogues showed that the most feasible position for the drug to interact with the receptor was found to be with analog 5 with an energy value of -12.3503 kcal/mole. Further, physicochemical properties were performed to evaluate the molecule’s capability of being druglikeness. All compounds under study had passed this filtering process and analog 5 possessed better values than the co-crystallized ligand. Second-generation CDK inhibitors in confirmed clinical trials are targeted against both CDK4/CDK6 which can inhibit only cell cycle progression and has no apoptotic inducing activity towards myeloma cells. This study relates the importance of novel molecules showing selective interaction towards CDK6 and the greater possibility of selective CDK6 inhibitors in cancer therapy.
Acute lymphoblastic leukemia can be controlled by inhibition of the cyclin-dependent kinase 6 –Retinoblastoma (CDK6-Rb) pathway. In this study, CDK6, a key regulator that allows progression through G1 and then G1/S transition of cell cycle, was used as target. Docking studies using ArgusLab with known flavonol CDK6 inhibitors and computationally designed analogues showed that the most feasible position for the drug to interact with the receptor was found to be with analog 5 with an energy value of -12.3503 kcal/mole. Further, physicochemical properties were performed to evaluate the molecule’s capability of being druglikeness. All compounds under study had passed this filtering process and analog 5 possessed better values than the co-crystallized ligand. Second-generation CDK inhibitors in confirmed clinical trials are targeted against both CDK4/CDK6 which can inhibit only cell cycle progression and has no apoptotic inducing activity towards myeloma cells. This study relates the importance of novel molecules showing selective interaction towards CDK6 and the greater possibility of selective CDK6 inhibitors in cancer therapy.
Keywords : Acute lymphoblastic leukemia, CDK6-Rb pathway, G1/S phase, cell cycle,in silico bioavailability analysis, physicochemical properties.
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