Abstracts from the Human Genome Meeting 2018

Activating mutations of fibroblast growth factor receptor 3 (FGFR3) cause various skeletal dysplasias and are also associated with certain cancers.Because there are no known specific pharmaceutical inhibitors of FGFR3, we established a cell-based protein translocation assay system that can monitor FGFR3 activity and be used for high throughput screening of complex mixtures.With this system we identified ethanol extract from a plant as a FGFR3 inhibitor and performed bioassay-guided fractionation to identify potent active fractions.The functionality of extract and active fractions were validated in vitro in FGFR3-activated primary multiple myeloma cells.The therapeutic efficacy and safety of the active fractions were further assessed in FGFR3 ACH mice, an achondroplasia mouse model.Oral administration significantly improved growth and dwarfism-related clinical features of the FGFR3 ACH mice.Our results demonstrate the applicability of this discovery approach.The identified plant extracts and active factions hold therapeutic potential for the treatment of FGFR3-activated skeletal dysplasias and cancers.