Discussion

This presentation covers the hit finding and validation process for natural products with anti-cancer properties in the Marine Fungi program. Secondary metabolities from marine fungal sources were screened for their effect on the viability and proliferation of a subset of the NCI60 panel of cancer cell lines. Active compounds of interest were profiled in a phenotypic format using a luciferase readout (Cell-Titre-Glo) . FACS based analyses (Phosphoflow), bioinformatics tools (COMPARE – NCI) and affinity approaches (Mass Spectroscopy) were used to identify potential cellular targets, oncogenic pathways and mechanisms of action. A panel of in-vitro toxicological, physico-chemical and PK assays were used to prioritise compounds for subsequent maximum tolerable dose and xenograft studies in mouse models.