For research use only. Not for therapeutic Use.
FIIN-3 is an irreversible inhibitor of FGFR with an IC50 of 13.1, 21, 31.4, and 35.3 nM for FGFR1, FGFR2, FGFR3 and FGFR4, respectively.
FIIN-3 potently inhibits both WT FGFRs (EC50 in the 1- to 41-nM range) and the gatekeeper mutant of FGFR2 (EC50 of 64 nM). FIIN-3 also strongly inhibits EGFR, with an EC50 of 43 nM. FIIN-3 shows good potency against gatekeeper mutant V564F; FIIN-3 also is potent against the gatekeeper-plus-1 mutant E565K; FIIN-3 also displays antiproliferative activity (with an EC50 of 135 nM) against Ba/F3 cells transformed by the EGFR vIII fusion protein, which has a WT EGFR kinase domain. FIIN-3 shows even better activity against EGFR mutant L858R (EC50 of 17 nM) and moderate activity, displaying an EC50 of 231 nM, against the EGFR mutant L858R/T790M mutant. In WT FGFR2 Ba/F3 cells, FIIN-3 completely inhibits the FGFR2 autophosphorylation on Tyr656/657 at concentrations as low as 3 nM. In FGFR2 V564M Ba/F3 cells, FIIN-3 is capable of inhibiting the FGFR2 mutant V564M autophosphorylation with partial inhibition at 100 nM and complete inhibition observed at 300 nM[1].
| Catalog Number | I002130 |
| CAS Number | 1637735-84-2 |
| Synonyms | N-[4-[[(2,6-dichloro-3,5-dimethoxyphenyl)carbamoyl-[6-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide |
| Molecular Formula | C34H36Cl2N8O4 |
| Purity | ≥95% |
| InChI | InChI=1S/C34H36Cl2N8O4/c1-5-30(45)40-24-8-6-22(7-9-24)20-44(34(46)41-33-31(35)26(47-3)18-27(48-4)32(33)36)29-19-28(37-21-38-29)39-23-10-12-25(13-11-23)43-16-14-42(2)15-17-43/h5-13,18-19,21H,1,14-17,20H2,2-4H3,(H,40,45)(H,41,46)(H,37,38,39) |
| InChIKey | SFLKJNSBBVSPFE-UHFFFAOYSA-N |
| SMILES | CN1CCN(CC1)C2=CC=C(C=C2)NC3=CC(=NC=N3)N(CC4=CC=C(C=C4)NC(=O)C=C)C(=O)NC5=C(C(=CC(=C5Cl)OC)OC)Cl |
| Reference | [1]. Tan L et al. Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors. Proc Natl Acad Sci U S A, 2014 Nov 11, 111(45):E4869-77 |
