| References: |
FIIN-2 is a potent, selective, irreversible and the next-generation covalent FGFR inhibitor. FIIN-2 is the first inhibitor that can potently inhibit the proliferation of cells dependent upon the gatekeeper mutants of FGFR1 or FGFR2, which confer resistance to first-generation clinical FGFR inhibitors such as NVP-BGJ398 and AZD4547. FIIN-2 also binds in the DFG-out mode despite lacking a functional group necessary to occupy the pocket vacated upon the DFG-out flip. Structural analysis reveals that the covalent bond between FIIN-2 and a cysteine, uniquely present in the glycine-rich loop of FGFR kinases, facilitates the DFG-out conformation, which together with the internal flexibility of FIIN-2 enables FIIN-2 to avoid the steric clash with the gate-keeper mutation that causes the ponatinib resistance. The structural data provide a blueprint for the development of next generation anticancer inhibitors through combining the salient inhibitory mechanisms of ponatinib and FIIN-2. For the detailed information of FIIN-2, the solubility of FIIN-2 in water, the solubility of FIIN-2 in DMSO, the solubility of FIIN-2 in PBS buffer, the animal experiment (test) of FIIN-2, the cell expriment (test) of FIIN-2, the in vivo, in vitro and clinical trial test of FIIN-2, the EC50, IC50,and affinity,of FIIN-2, For the detailed information of FIIN-2, the solubility of FIIN-2 in water, the solubility of FIIN-2 in DMSO, the solubility of FIIN-2 in PBS buffer, the animal experiment (test) of FIIN-2, the cell expriment (test) of FIIN-2, the in vivo, in vitro and clinical trial test of FIIN-2, the EC50, IC50,and affinity,of FIIN-2, Please contact DC Chemicals. |
