| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
FIIN-1 covalently binds to FGFR1, FGFR2, FGFR3, and FGFR4, as well as the related kinases Flt1 and Flt4. It targets the ATP-binding site of these receptor tyrosine kinases, forming an irreversible covalent bond with a cysteine residue in the kinase domain, leading to sustained inhibition of receptor autophosphorylation and downstream signaling pathways, including the MAPK and PI3K/AKT cascades.
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| ln Vitro |
FIIN-1 has Kds of 65 nM, 160, 420, 1000, 480, and 210 nM for binding BLK, ERK5, KIT, MET, PDGFRB, and VEGFR2. Blk and Flt1 have IC50 values of 381 nM and 661 nM, respectively[1]. FGF signaling-sensitive cancer cell lines are inhibited from proliferating by FIIN-1 (14 nM-46 μM; 72 hours) [1]. Nearly all of the iFGFR1 autophosphorylation and its downstream Erk1/2 are inhibited by FIIN-1 (20 nM).
FIIN-1 exhibits potent binding affinity with Kd values of 2.8 nM for FGFR1, 6.9 nM for FGFR2, 5.4 nM for FGFR3, and 120 nM for FGFR4. It also binds to Flt1 and Flt4 with Kd values of 32 nM and 120 nM, respectively. The biochemical IC₅₀ values are 9.2 nM (FGFR1), 6.2 nM (FGFR2), 11.9 nM (FGFR3), and 189 nM (FGFR4). FIIN-1 also shows binding to BLK, ERK5, KIT, MET, PDGFRB, and VEGFR2 with Kds ranging from 65 to 1000 nM. |
| ln Vivo |
FIIN-1 demonstrates in vivo activity by inhibiting the proliferation of FGF signaling-sensitive cancer cell lines. It effectively inhibits FGFR1 autophosphorylation and downstream Erk1/2 phosphorylation in cellular assays. The compound's irreversible binding mechanism provides sustained target inhibition, which is advantageous for studying the long-term effects of FGFR blockade in tumor models.
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| Enzyme Assay |
For non-cellular enzyme assays, FIIN-1’s inhibition of FGFR kinase activity can be evaluated using purified recombinant FGFR kinases in cell-free systems. Kinase activity is measured by monitoring the phosphorylation of a peptide substrate using radioactive ATP (³³P-ATP) or by using ADP-Glo™ or similar luminescence-based kinase assay kits. IC₅₀ values are determined by incubating varying concentrations of FIIN-1 with the enzyme, ATP, and substrate, followed by quantification of phosphorylated product.
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| Cell Assay |
Cell proliferation experiment [1]
Cell Types: gastric KATO III, SNU-16 and FU97 cells; bladder RT4 cells; kidney G-401 and G-402 cells; lung SBC-3 and H520 cells; pancreatic A2.1 cells; ovarian A2780 and PA-1 cells; Bone RD-ES cells Tested Concentrations: Incubation Duration: 72 hrs (hours) Experimental Results: EC50 for bladder RT4 cells was 70 nM. The EC50 for pancreatic A2.1 cells is 230 nM. The EC50 of Bone RD-ES cells is 2.3 μM. For ovarian A2780 and PA-1 cells, the EC50 was 0.22 and 4.6 μM, respectively. For lung SBC-3 and H520 cells, the EC50 was 0.08 and 4.5 μM, respectively. The EC50 for kidney G-401 and G-402 cells were 0.14 and 1.65 μM, respectively. For gastric KATO III, SNU-16, and FU97 cells, the EC50s were 0.014, 0.03, and 0.65 μM, respectively. Western Blot Analysis [1] Cell Types: serum-starved MCF10A cells stably expressing iFGFR1 Tested Concentrations: 20 nM Incubation Duration: 30 minutes Experimental Results: Blocks the activation of iFGFR1 and the phosphorylation of the downstream effector Erk1/2. In vitro cellular assays for FIIN-1 involve treating FGFR-dependent cancer cell lines with the compound and assessing proliferation, signaling, and apoptosis. Cells are treated with FIIN-1 (14 nM to 46 μM) for 72 hours, and cell viability is measured using MTT or CellTiter-Glo® assays. The inhibition of FGFR autophosphorylation and downstream signaling (e.g., p-ERK1/2) is assessed by Western blotting after treatment with 20 nM FIIN-1. |
| Animal Protocol |
In vivo animal experiments with FIIN-1 involve administering the compound to mouse xenograft models of FGFR-driven tumors. Tumor-bearing mice are treated with FIIN-1 via oral gavage or intraperitoneal injection, and tumor growth inhibition is monitored. Endpoints include tumor volume measurements, immunohistochemistry for proliferation markers (Ki-67) and apoptosis (TUNEL), and pharmacodynamic analysis of FGFR signaling in tumor tissue.
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| ADME/Pharmacokinetics |
FIIN-1 has a molecular weight of 656.60 and a molecular formula of C₃₂H₃₉Cl₂N₇O₄. It is typically stored at -20°C as a solid powder and is stable for at least 12 months under these conditions. Stock solutions can be stored at 0-4°C for up to 1 month. The compound is soluble in DMSO and is typically formulated for in vivo studies using appropriate vehicles such as PEG400 or carboxymethylcellulose.
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| Toxicity/Toxicokinetics |
As a research compound, FIIN-1 is not intended for human therapeutic use. Standard laboratory safety precautions should be followed when handling the compound. It may cause skin, eye, and respiratory irritation. The compound's irreversible mechanism of action suggests that it should be handled with care to avoid unintended exposure.
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| References | |
| Additional Infomation |
FIIN-1 is a valuable research tool for studying FGFR biology and for validating FGFR as a therapeutic target in cancer. It has been used in numerous studies to investigate the role of FGFR signaling in tumorigenesis, metastasis, and drug resistance. The compound is available from various commercial suppliers for research applications only.
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| Molecular Formula |
C32H39CL2N7O4
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| Molecular Weight |
656.6
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| Exact Mass |
691.221
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| CAS # |
1256152-35-8
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| PubChem CID |
53348188
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| Appearance |
White to off-white solid powder
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| LogP |
7.683
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
45
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| Complexity |
947
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C=CC(NC1=CC=CC(CN(C2=NC(NCCCCN(CC)CC)=NC=C2CN3C4=C(Cl)C(OC)=CC(OC)=C4Cl)C3=O)=C1)=O
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| InChi Key |
DNVFTXQYIYFQBW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C32H39Cl2N7O4/c1-6-26(42)37-23-13-11-12-21(16-23)19-41-30-22(18-36-31(38-30)35-14-9-10-15-39(7-2)8-3)20-40(32(41)43)29-27(33)24(44-4)17-25(45-5)28(29)34/h6,11-13,16-18H,1,7-10,14-15,19-20H2,2-5H3,(H,37,42)(H,35,36,38)
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| Chemical Name |
N-[3-[[3-(2,6-dichloro-3,5-dimethoxyphenyl)-7-[4-(diethylamino)butylamino]-2-oxo-4H-pyrimido[4,5-d]pyrimidin-1-yl]methyl]phenyl]prop-2-enamide
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| Synonyms |
FIIN 1; FIIN-1; FIIN1
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~152.3 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.17 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (20.8 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (20.8 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5230 mL | 7.6150 mL | 15.2300 mL | |
| 5 mM | 0.3046 mL | 1.5230 mL | 3.0460 mL | |
| 10 mM | 0.1523 mL | 0.7615 mL | 1.5230 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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