Name: FIIN-2
Price: 294.00 USD

- Overview
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    Background
    
    FIIN-2 is an irreversible inhibitor of FGFR1–4 with IC50 values of 3.1, 4.3, 27, and 45 nM, respectively. FIIN-2 also moderately inhibited EGFR, with an IC50 of 204 nM. The Cys491 of FGFR2 is the primary labeled site for FIIN-2 binding [1].FIIN-2 is the first class of inhibitors that can potently inhibit the proliferation of cells dependent upon the gatekeeper mutants of FGFR1 or FGFR2. The co-crystal structure of FGFR4 with FIIN-2 was reported, which unexpectedly exhibits a “DFG-out” covalent binding mode. FIIN-2 maintains the pyrimido[4,5-d] pyrimidinone core of FIIN-1 but removes the two chlorine atoms, which are crucial for FIIN-1’s potency against FGFR. FIIN-2 maintains the ability to form a covalent bond with the P-loop cysteine but alter the selectivity profile versus other kinases. Compared with FIIN-1, FIIN-2 displayed strong binding to FGFRs and exhibited good overall kinase selectivity. FIIN-2 exhibited much less affinity for EGFR, but FIIN-3 potently bound to WT EGFR and to a subset of EGFR mutants. [1]FIIN-2 inhibited proliferation of FGFR1-4 Ba/F3 cells with EC50s in the nanomolar range and were especially potent against FGFR2, with EC50s in the 1-nM range. FIIN-2 also inhibited the FGFR2 V564M gatekeeper mutant Ba/F3 cells, with EC50s of 58 nM, whereas FIIN-1 and BGJ398 had EC50s of over 1.0 μM against this mutant. FIIN-2 showed good potency against gatekeeper mutant V564F. In contrast, FIIN-2 was fourfold less potent (EC50 of 506 nM). FIIN-2 was inactive up to a concentration of 1.8 μM against EGFR L858R. FIIN-2 showed rather poor potency against protein kinase FLT1 (FLT1). In WT FGFR2 Ba/F3 cells, FIIN-2 completely inhibited the FGFR2 autophosphorylation on mutations of Tyr656/657 and V564M at concentrations of 3 nM and 300 nM, respectively. [1]
- Properties
  - Alternative Name
    
    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
    
    CAS Number
    
    1633044-56-0
    
    Molecular Formula
    
    C35H38N8O4
    
    Molecular Weight
    
    634.73
    
    Appearance
    
    A solid
    
    Purity
    
    99.43%
    
    Solubility
    
    ≥31.75 mg/mL in DMSO; insoluble in H2O; ≥3.39 mg/mL in EtOH with gentle warming
    
    Storage
    
    Store at -20°C
    
    * For Research Use Only
- Reference
  - 1. Dunkel H, Chaverra M, et al. "FGF signaling is required for chemokinesis and ventral migration of trunk neural crest cells." Dev Dyn. 2020;10.1002/dvdy.190. PMID:32390246

FIIN-2

FIIN-2

Background

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