| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
FGFR4 (IC50 = 0.7 nM)
FGFR4-IN-1 targets fibroblast growth factor receptor 4 (FGFR4), a receptor tyrosine kinase that is activated upon binding with specific ligands such as FGF19. FGFR4 activation leads to receptor dimerization and autophosphorylation, initiating downstream signaling cascades that influence gene expression. FGFR4-IN-1 is a selective FGFR4 kinase inhibitor with an IC50 of 0.7 nM. |
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| ln Vitro |
FGFR4-IN-1 exhibits a significant IC50 of 7.8 nM in inhibiting the proliferation of HuH-7 hepatocellular carcinoma cells[1].
In vitro, FGFR4-IN-1 potently inhibits FGFR4 kinase activity with an IC50 of 0.7 nM. It significantly inhibits the proliferation of HuH-7 hepatocellular carcinoma cells with an IC50 of 7.8 nM. The compound blocks FGFR4 signaling, thereby inhibiting tumor cell proliferation and survival. FGFR4-IN-1 demonstrates selectivity for FGFR4 over other kinases. |
| ln Vivo |
In vivo, FGFR4-IN-1 reduces tumor growth by 62.7% and 70.8% in a Huh7 mouse xenograft model when administered at doses of 30 and 100 mg/kg per day, respectively. The compound's efficacy in hepatocellular carcinoma models supports its potential as an anti-cancer therapeutic. FGFR4-IN-1 inhibits tumor growth by blocking FGFR4 signaling in vivo.
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| Enzyme Assay |
The in vitro kinase inhibition assay for FGFR4-IN-1 involves measuring its inhibitory effect on FGFR4 kinase activity. Recombinant FGFR4 enzyme is incubated with varying concentrations of FGFR4-IN-1, ATP, and a peptide substrate. The extent of phosphorylation is measured using radiometric or fluorescence-based detection methods. The IC50 is calculated from dose-response curves. FGFR4-IN-1 inhibits FGFR4 with an IC50 of 0.7 nM.
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| Cell Assay |
In vitro cellular assays for FGFR4-IN-1 involve treating hepatocellular carcinoma cell lines (e.g., HuH-7) with varying concentrations of the compound. Cell proliferation is assessed using MTT, CCK-8, or colony formation assays. FGFR4 phosphorylation and downstream signaling proteins (e.g., ERK, AKT) are measured by Western blotting. FGFR4-IN-1 inhibits HuH-7 cell proliferation with an IC50 of 7.8 nM.
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| Animal Protocol |
In vivo animal experiments for FGFR4-IN-1 use mouse xenograft models of hepatocellular carcinoma. HuH-7 tumor-bearing mice are administered FGFR4-IN-1 orally at doses of 30 and 100 mg/kg per day. Tumor volume is measured regularly using calipers. At the end of the study, tumors are excised and analyzed for FGFR4 phosphorylation, apoptosis markers, and proliferation markers. FGFR4-IN-1 reduces tumor growth by 62.7% and 70.8% at 30 and 100 mg/kg, respectively.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of FGFR4-IN-1 have been characterized in preclinical studies. The compound has a molecular weight of 493.52 (C24H27N7O5). As a small molecule kinase inhibitor, FGFR4-IN-1 is expected to have oral bioavailability and reasonable tissue distribution. Specific PK parameters including half-life, Cmax, and AUC would be available from preclinical pharmacokinetic studies.
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| Toxicity/Toxicokinetics |
FGFR4-IN-1 has been evaluated in preclinical studies for hepatocellular carcinoma. As a selective FGFR4 inhibitor, it is expected to have a manageable toxicity profile. Potential adverse effects may include those associated with FGFR inhibition, such as phosphate homeostasis dysregulation. Complete toxicology data including acute, repeated-dose, and genotoxicity studies would be available from preclinical development programs.
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| References | |
| Additional Infomation |
FGFR4-IN-1 (CAS#: 1708971-72-5) is a potent and selective FGFR4 kinase inhibitor with an IC50 of 0.7 nM. It significantly inhibits HuH-7 hepatocellular carcinoma cell proliferation with an IC50 of 7.8 nM and reduces tumor growth in mouse xenograft models. FGFR4-IN-1 is not approved for clinical use and remains an investigational compound for FGFR4-driven cancers.
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| Molecular Formula |
C24H27N7O5
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|---|---|
| Molecular Weight |
493.524
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| Exact Mass |
493.207
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| Elemental Analysis |
C, 58.41; H, 5.51; N, 19.87; O, 16.21
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| CAS # |
1708971-72-5
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| Related CAS # |
1708971-72-5
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| PubChem CID |
118036840
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
875.4±65.0 °C at 760 mmHg
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| Flash Point |
483.3±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.649
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| LogP |
-0.36
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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 |
8
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| Heavy Atom Count |
36
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| Complexity |
835
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1CC(N(CC1)CC1=C(C=O)N=C2C(=C1)CCCN2C(NC1C=C(C(C#N)=CN=1)NCCOC)=O)=O
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| InChi Key |
ZTYSXMGILYNNJX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H27N7O5/c1-35-7-4-26-19-10-21(27-12-18(19)11-25)29-24(34)31-5-2-3-16-9-17(20(14-32)28-23(16)31)13-30-6-8-36-15-22(30)33/h9-10,12,14H,2-8,13,15H2,1H3,(H2,26,27,29,34)
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| Chemical Name |
N-[5-cyano-4-(2-methoxyethylamino)pyridin-2-yl]-7-formyl-6-[(3-oxomorpholin-4-yl)methyl]-3,4-dihydro-2H-1,8-naphthyridine-1-carboxamide
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| Synonyms |
FGFR4-IN-1; FGFR4-IN1; FGFR4-IN 1
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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: ~6.4 mg/mL (~13 mM)
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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 | 2.0263 mL | 10.1313 mL | 20.2626 mL | |
| 5 mM | 0.4053 mL | 2.0263 mL | 4.0525 mL | |
| 10 mM | 0.2026 mL | 1.0131 mL | 2.0263 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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