| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
FGFR4 6.5 nM (IC50) FGFR2 505 nM (IC50)
FGFR4 (fibroblast growth factor receptor 4). FGFR4-IN-5 is a selective covalent FGFR4 inhibitor that binds irreversibly to a specific cysteine residue in the FGFR4 ATP-binding pocket, leading to sustained target inhibition. |
|---|---|
| ln Vitro |
FGFR4-IN-5 inhibits FGFR4 with an IC50 of 6.5 nM. It is a potent and selective covalent FGFR4 inhibitor. In vitro, it blocks FGFR4 phosphorylation and downstream signaling, leading to cell cycle arrest and apoptosis in FGFR4-dependent liver cancer cell lines.
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| ln Vivo |
FGFR4-IN-5 (oral gavage; 10 mg/kg; single dose) reveals a high Cmax, low clearance, the Cmax values are 423 ng/ml, 588 ng/ml, and 2820 ng/ml in mice, rat and cynamolgus monkey, respectively. And the oral bioavailability are 20, 12, and 27% in mouse, rat, and cyno, respectively[1]. FGFR4-IN-5 (oral gavage; 100 mg/kg; twice daily; 28 days) exhibits strong antitumor activity in an orthotopic Hep3B HTX model[1]. FGFR4-IN-5 (oral gavage; 10, 30, and 100 mg/kg; twice daily; 11 days) results in dose-dependent growth inhibition of resistant tumors. Tumor Regression is observed at 30 and 100 mg/kg, with %ΔT/ΔC of 67% and 70%, respectively. However, treatment with sorafenib at 100 mg/kg once daily does not provide any benefit in vivo[1].
FGFR4-IN-5 exhibits strong anti-tumor activity in vivo. It shows significant tumor growth inhibition in hepatocellular carcinoma xenograft models and can be used for hepatocellular carcinoma research. Its covalent binding mechanism provides sustained target inhibition, making it suitable for in vivo efficacy studies. |
| Enzyme Assay |
Cell-free FGFR4 kinase assays are performed using recombinant human FGFR4 enzyme. The compound is pre-incubated with the enzyme for 30 minutes to allow covalent binding, followed by addition of ATP and a peptide substrate. Kinase activity is measured using a luminescence-based ADP detection kit. IC50 (6.5 nM) is calculated from dose-response curves.
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| Cell Assay |
FGFR4-dependent human HCC cell lines are seeded in 96-well plates and treated with increasing concentrations of FGFR4-IN-5 for 72 hours. Cell viability is assessed using the CellTiter-Glo reagent. The effect on FGFR4 phosphorylation and downstream signaling (p-ERK) is measured by Western blotting. IC50 for cell proliferation is determined.
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| Animal Protocol |
Animal/Disease Models: Hep3B cell bearing mice model[1]
Doses: 100 mg/kg Route of Administration: Oral gavage; 100 mg/kg; twice (two times) daily; 28 days Experimental Results: Resulted in tumor regression and sustained growth inhibition. Animal/Disease Models: Sorafenib-resistant tumors established to mice bearing Huh7 tumors[1] Doses: 10, 30, and 100 mg/kg Route of Administration: Oral gavage; 10, 30, and 100 mg/kg; twice (two times) daily; 11 days Experimental Results: Resulted in dose-dependent growth inhibition of resistant tumors. For in vivo studies, FGFR4-IN-5 is administered orally to mice bearing FGFR4-driven HCC xenografts. A typical dose is 10 mg/kg as a single oral gavage dose. Tumor volumes are measured with calipers. At study termination, tumors are excised for analysis of FGFR4 phosphorylation and downstream signaling. Efficacy is assessed by tumor growth inhibition. |
| ADME/Pharmacokinetics |
No specific PK data are reported for FGFR4-IN-5. As a small-molecule covalent inhibitor (MW not specified, CAS 1628793-01-0), it is orally active. It is soluble in DMSO for in vitro studies. For in vivo studies, it is typically formulated in a suitable vehicle such as 0.5% methylcellulose or a DMSO/PEG300/Tween-80/saline mixture. PK parameters have not been characterized.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for FGFR4-IN-5. As a selective covalent FGFR4 inhibitor, potential on-target toxicities may include effects on FGFR4-dependent tissues, such as liver metabolism and bile acid regulation. Comprehensive toxicological assessments have not been published. The compound is for research use only.
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| References | |
| Additional Infomation |
Other information: FGFR4-IN-5 (CAS 1628793-01-0) is a research compound and not FDA-approved. It is a potent and selective covalent FGFR4 inhibitor with an IC50 of 6.5 nM. It exhibits strong anti-tumor activity in vivo and is valuable for hepatocellular carcinoma research. For research use only. Synonyms: FGFR4-IN-5.
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| Molecular Formula |
C23H23CL2N5O5
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|---|---|
| Molecular Weight |
520.37
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| Exact Mass |
519.107
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| CAS # |
1628793-01-0
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| PubChem CID |
90436886
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| Appearance |
White to off-white solid powder
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| LogP |
2.9
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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 |
7
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| Heavy Atom Count |
35
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| Complexity |
831
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O(C1=CC(OC)=C(Cl)C(C2=CC3C(N(C)C2=O)=NC(N[C@H]2[C@@H](NC(C=C)=O)COC2)=NC=3)=C1Cl)C
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| InChi Key |
ZIJVLVUPDVUSMA-UONOGXRCSA-N
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| InChi Code |
InChI=1S/C23H23Cl2N5O5/c1-5-17(31)27-13-9-35-10-14(13)28-23-26-8-11-6-12(22(32)30(2)21(11)29-23)18-19(24)15(33-3)7-16(34-4)20(18)25/h5-8,13-14H,1,9-10H2,2-4H3,(H,27,31)(H,26,28,29)/t13-,14+/m0/s1
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| Chemical Name |
N-[(3R,4S)-4-[[6-(2,6-dichloro-3,5-dimethoxyphenyl)-8-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]oxolan-3-yl]prop-2-enamide
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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 (192.17 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to 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: ≥ 2.5 mg/mL (4.80 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9217 mL | 9.6085 mL | 19.2171 mL | |
| 5 mM | 0.3843 mL | 1.9217 mL | 3.8434 mL | |
| 10 mM | 0.1922 mL | 0.9609 mL | 1.9217 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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