FIIN-2

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

FIIN-2 是一种不可逆的泛 FGFR 抑制剂，抑制 FGFR1/2/3/4，IC50 分别为 3.09 nM、4.3 nM、27 nM 和 45.3 nM。

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.

FIIN-2 potently inhibits WT FGFRs (EC50s in the 1- to 93-nM range) and the gatekeeper mutant of FGFR2 (EC50 of 58 nM). FIIN-2 also moderately inhibits EGFR, with an IC50 of 204 nM. FIIN-2 inhibits proliferation of FGFR1-4 Ba/F3 cells with EC50s in the single- to double-digit nanomolar range and are especially potent against FGFR2, with EC50s in the 1-nM range. FIIN-2 shows good potency against gatekeeper mutant V564F.

Treatment of fish in the embryonic state with either FIIN-2 causes defects to the posterior mesoderm similar to the phenotypes reported following genetic knockdown of FGFR or treatment with other reported FGFR inhibitors. FIIN-2 causes mild or severe phenotypes to the tail morphogenesis in all treated embryonic zebrafish.

FIIN2 | FIIN 2 | FIIN-2

GPCR/G Protein

Dopamine Receptor

FGFR1| FGFR2| FGFR3| FGFR4

Cancer

——

1633044-56-0

634.73

C35H38N8O4

>98% (HPLC)

DMSO : ≥ 30 mg/mL 47.26 mM

CN1CCN(CC1)c1ccc(cc1)Nc1ncc2CN(C(=O)N(c2n1)Cc1ccc(cc1)NC(=O)C=C)c1cc(cc(c1)OC)OC

N-(4-((3-(3,5-dimethoxyphenyl)-7-((4-(4-methylpiperazin-1-yl)phenyl)amino)-2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidin-1(2H)-yl)methyl)phenyl)acrylamide

(-20℃)

With Ice Pack

≥ 2 years