Deciphering the Synergistic Mechanism of Cortistatin towards Cancer Targets Using Network Pharmacology Approach

Abstract: Steroidal alkaloid cortistatin is a promising marine natural compound isolated from sponges Corticium simplex. Experimental studies and clinical evidence have shown that its derivatives curative effect in patients with autoimmune disorders, HIV infection several types of cancer. The objective our study was to examine the potential cancer-related therapeutic objectives Cortistatin using network pharmacology method, which computational approach, including inverse pharmacophore research, enrichment analysis, molecular docking dynamics study. Systematic protocol also involves assessment ADMET parameters define pharmacokinetic profile cortistatin. Inverse search method used for target fishing proteins were ranked based on graph theory approach. Cancer proteins, namely HSP90, EGFR, CDK2, MMP13, MAPK13, AR, ESR1, PTPN11 SRC, classified as top-ranking according parameters, MCC, DMNC, MNC, Degree(Local-based methods), EPC, Bottleneck, Eccentricity, Closeness, Radiality, Betweenness, Stress(Global-based methods) Clustering Coefficient. Enrichment established Gene Ontology pathway analysis these play vital role cancer pathways, FaxO Signalling Ras pathways tyrosine metabolism. Molecular dynamic simulation proposed found be stable conformers generated after 3ns consistent inter-molecular interactions. current summarized here would provide broad perspective new insights into future development therapy strategies. Key words: Cortistatin, Marine product, docking, Network pharmacology, targets, Pharmacokinetics.