Description
Dabogratinib(TYRA-300) , a 3-pyridylindazole analog, is a reversible and selective inhibitor of FGFR3 with an IC50 of 11 nM in Ba/F3 cells. It also exhibit potent activity in human bladder cancer cell lines harboring FGFR3 activating fusions or mutations.
Mode of action
Upon oral administration, dabogratinib specifically targets and binds to certain FGFR3 activating gene alterations, and specifically the gatekeeper mutants V555L/M. This blocks FGFR3-mediated signaling and leads to an inhibition of tumor cell proliferation in FGFR3-overexpressing cells. FGFR3, a receptor tyrosine kinase, is involved in angiogenesis and in the proliferation, differentiation, and survival of tumor cells. FGFR3 expression is associated with poor prognosis. It is overexpressed by certain tumor cell types.
