| Size | Price | Stock | Qty |
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| 1mg |
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| 100mg | |||
| Other Sizes |
| Targets |
FIIN-4 targets FGFR1, FGFR2, FGFR3, and FGFR4 by forming a covalent bond with a cysteine residue in the kinase domain. This irreversible mechanism of action leads to sustained inhibition of FGFR kinase activity, blocking receptor autophosphorylation and downstream signaling pathways, including RAS-MAPK and PI3K-AKT, which are critical for tumor cell proliferation, survival, and metastasis.
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|---|---|
| ln Vitro |
FIIN-4 exhibits potent inhibitory activity with IC₅₀ values of 2.6 nM for both FGFR1 and FGFR2, 5.6 nM for FGFR3, and 9.2 nM for FGFR4. This high potency against all four FGFR family members makes FIIN-4 a valuable tool for studying FGFR-driven cancers. Its covalent binding mechanism provides prolonged target engagement compared to reversible inhibitors.
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| ln Vivo |
FIIN-4 demonstrates in vivo efficacy in inhibiting metastatic tumor growth. As an orally active compound, it is suitable for administration in animal models of cancer. The compound has been utilized in research to investigate its efficacy in inhibiting metastatic tumor growth, making it a valuable tool in cancer biology studies.
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| Enzyme Assay |
For non-cellular enzyme assays, FIIN-4’s inhibition of FGFR kinase activity can be evaluated using purified recombinant FGFR kinases. Kinase activity is measured using radiometric or luminescence-based assays (e.g., ADP-Glo™) with a peptide substrate and ATP. The covalent nature of the inhibitor requires pre-incubation steps to allow for irreversible binding before substrate addition. IC₅₀ values are determined by fitting dose-response curves.
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| Cell Assay |
In vitro cellular assays for FIIN-4 involve treating FGFR-dependent cancer cell lines with the compound and assessing cell viability, proliferation, and signaling. Cells are treated with varying concentrations of FIIN-4, and cell viability is measured using MTT or CellTiter-Glo® assays. The inhibition of FGFR autophosphorylation and downstream signaling (p-ERK, p-AKT) is assessed by Western blotting.
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| Animal Protocol |
In vivo animal experiments with FIIN-4 involve oral administration to mouse xenograft models of FGFR-driven tumors, particularly metastatic breast cancer models. Tumor growth inhibition is monitored, and pharmacodynamic markers such as FGFR phosphorylation in tumor tissue are assessed. The compound's oral bioavailability and covalent mechanism make it suitable for once-daily dosing regimens.
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| ADME/Pharmacokinetics |
FIIN-4 has a molecular weight of 634.73 and a molecular formula of C₃₅H₃₈N₈O₄. It is a solid at room temperature and is typically stored at -20°C. The compound is soluble in DMSO and other organic solvents. Purity is typically ≥99%. The compound is light-sensitive and should be protected from light during storage and handling.
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| Toxicity/Toxicokinetics |
Toxicological data for FIIN-4 are limited as it is a research compound not intended for clinical use. Standard laboratory safety precautions should be followed when handling the compound. The covalent binding mechanism may raise concerns regarding off-target reactivity, and appropriate selectivity profiling should be conducted.
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| Additional Infomation |
FIIN-4 is a first-in-class covalent FGFR inhibitor used in cancer research. It is utilized to investigate the efficacy of FGFR inhibition in metastatic tumor growth. The compound's covalent binding mechanism and oral bioavailability make it a valuable tool for in vivo pharmacology studies. It is available from various commercial suppliers for research applications only.
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| Molecular Formula |
C35H38N8O4
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|---|---|
| Molecular Weight |
634.741
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| Exact Mass |
634.301
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| CAS # |
2093088-81-2
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| PubChem CID |
154723923
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.666
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| LogP |
1.82
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
47
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| Complexity |
1040
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1N(C2C=C(C=C(C=2)OC)OC)CC2=CN=C(N=C2N1CC1C=CC=C(C=1)NC(C=C)=O)NC1C=CC(=CC=1)N1CCN(C)CC1
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| InChi Key |
NQUHMXJRVOMTBY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C35H38N8O4/c1-5-32(44)37-27-8-6-7-24(17-27)22-43-33-25(23-42(35(43)45)29-18-30(46-3)20-31(19-29)47-4)21-36-34(39-33)38-26-9-11-28(12-10-26)41-15-13-40(2)14-16-41/h5-12,17-21H,1,13-16,22-23H2,2-4H3,(H,37,44)(H,36,38,39)
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| Chemical Name |
N-[3-[[3-(3,5-dimethoxyphenyl)-7-[4-(4-methylpiperazin-1-yl)anilino]-2-oxo-4H-pyrimido[4,5-d]pyrimidin-1-yl]methyl]phenyl]prop-2-enamide
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| Synonyms |
FIIN4; FIIN 4; FIIN-4
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5754 mL | 7.8772 mL | 15.7545 mL | |
| 5 mM | 0.3151 mL | 1.5754 mL | 3.1509 mL | |
| 10 mM | 0.1575 mL | 0.7877 mL | 1.5754 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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