In-Silico Exploitation of Roscovitine as Therapy Against Hepatocellular Carcinoma (HCC)

Abstract

Hepatocellular Carcinoma (HCC) is a fatal malignancy with poor prognosis due to late diagnosis and poor response of current therapeutic interventions. Inhibitors of Cyclin Dependent Kinases (CDKs), that promote metastasis, are potential drugs for late-stage malignancies. One such drug is Roscovitine, a potent CDK inhibitor being used as therapy for breast and prostate cancer. Our aim was to investigate the therapeutic effects of Roscovitine in HCC by identifying protein targets via in-silico techniques. Molecular docking of Roscovitine with other over-expressed kinases like p-21 Activated Kinases (PAKs) and Mitogen-Activated Protein Kinases (MAPKs) in HCC was performed via AutoDock Vina on PyRx. Complexes with low binding affinities were selected for Molecular Dynamics Simulation studies via iMODS to investigate their dynamic nature in a biological context. Analysis of MDS results suggest that c-Jun N-terminal Kinases (JNKs), belonging to the family of MAPKs, may also be potential targets of Roscovitine in addition to CDKs. Hence, bears potential as a viable therapeutic option against HCC and has to be taken up for experimental work