Computational Approach to Study Marine Derived Cortistatin a Molecular Mechanism as a Janus Kinase 3 Inhibitor

Cortistatin A is a natural product isolated from the marine sponge Corticium simplex has been considered as a therapeutic agent for autoimmune disorders, HIV infection as well as cancer.Janus kinases (JAKs) and signal transducer and activator of transcription (STAT) transcription factors play a promising role in either causing or participating in the tumorigenesis.Following our earlier studies on JAK-STAT pathway genes varied expression among the various types of breast cancer samples, JAK3 protein plays a crucial role in cancer pathway, thus we implement a feasible systems pharmacology method to explore JAK3 function.Our systematic Insilco approaches involve systems-based assessment of JAK3 role in cytokine signaling, ADMET a scale for pharmacokinetic and pharmacodynamics assessment, pharmacophore mapping of JAK3 and ligand Cortistatin A. Sequence level annotation of functional domains revealed similarity between the JAK family members namely JAK1, JAK2, JAK 3 and TYK2.Thus intermolecular interaction, molecular dynamics and simulation assessment of JAK3 with Cortistatin docked complex pattern applicable other members that shared the domain similarity.Thus, our present study proposes the system level of understanding about Cortistatin A agonist activity on JAK3 and suggesting the compound as a potent antiproliferative agent for cancer treatment.