FAISAL HASSAN TOBEIGEI1, REEM M. GAHTANI2, AHMAD SHAIKH2, AMER AL ALI3, NADER KAMELI4,5, HOSSAM KAMLI2, PRASANNA RAJAGOPALAN2,6,*
Oncology Research, Vol.29, No.5, pp. 305-318, 2021, DOI:10.32604/or.2022.025187
Abstract Malignant melanoma is characterized by both genetic and molecular alterations that activate phosphoinositide 3-kinase (PI3K), and RAS/BRAF pathways. In this work, through diversity-based high-throughput virtual screening we identified a lead molecule that selectively targets PI3K and BRAFV600E kinases. Computational screening, Molecular dynamics simulation and MMPBSA calculations were performed. PI3K and BRAFV600E kinase inhibition was done. A375 and G-361 cells were used for in vitro cellular analysis to determine antiproliferative effects, annexin V binding, nuclear fragmentation and cell cycle analysis. Computational screening of small molecules indicates compound CB-006-3 selectively targets PI3KCG (gamma subunit), PI3KCD (delta subunit) and BRAFV600E. Molecular dynamics simulation… More >
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