Molecular docking studies for NPACT ligands for the treatment of melanoma skin cancer

Abstract

Approximately 80% of deaths attributable to skin cancer are attributed to melanoma. The main reason for its life-threatening nature is its high tendency to metastasis. The outlook for melanoma patients with distal metastases is grim, as they have a median survival of only six months, despite the utilization of the most advanced treatments now available. The Extracellular signal-regulated kinase (ERK) pathway is the most frequently altered oncogene in melanoma. Phytochemicals are receiving significant recognition due to their minimal toxicity, affordable price, and widespread acceptance as dietary supplements. Preclinical investigations have revealed many cellular and molecular processes via which phytochemicals function in the prevention and treatment of metastatic melanoma.: In this study, we performed virtual screening of 464 phytoconstituents were obtained from the Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target (NPACT) database to identify novel ERK inhibitors.: Virtual screening carried out prediction of drug-likeness and molecular docking studies with 2OJG, protein target related to ERK pathway.: Nine compounds achieved better docking score as compared to co-crystallized ligand. The accuracy of the docking method was checked using re-docking. Picetannol and sulfurentin were identified as potential inhibitors with docking score of -9.2 and -8.2, respectively. These two phytoconstituents also found to be non-carcinogenic which was predicted using a free webtool, Swiss ADME.: Our finding suggests that Piceatannol has promising potential to be further explored as ERK-pathway inhibitor in treatment of melanoma