| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
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| Targets |
Lirafugratinib targets FGFR2 (IC50 = 3 nM). It is an irreversible inhibitor that covalently binds to the FGFR2 kinase domain, showing high selectivity over other FGFR family members (FGFR1, FGFR3, FGFR4) and the broader kinome. It also targets other FGFR family members but with lower potency.
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| ln Vitro |
In cell-free kinase assays using purified FGFR2 enzyme, Lirafugratinib shows potent inhibition (IC50 = 3 nM). In FGFR2-altered cancer cell lines (e.g., gastric, endometrial, intrahepatic cholangiocarcinoma), it inhibits cell proliferation with IC50 values in the low nanomolar range. It suppresses FGFR2 phosphorylation and downstream MAPK and PI3K-AKT signaling pathways.
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| ln Vivo |
In vivo, oral administration of Lirafugratinib in mouse xenograft models of FGFR2-driven cancers (e.g., gastric, cholangiocarcinoma) leads to dose-dependent tumor growth inhibition and tumor regression. The compound is well-tolerated at therapeutic doses, with a high safety margin.
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| Enzyme Assay |
The cell-free FGFR2 kinase inhibition assay is performed using recombinant human FGFR2 enzyme. Lirafugratinib (0.01-100 nM) is pre-incubated with FGFR2 and ATP in reaction buffer for 30-60 min. Substrate phosphorylation is measured using a luminescent kinase assay (e.g., ADP-Glo) or by transfer of 32P-ATP to a peptide substrate. IC50 is calculated.
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| Cell Assay |
FGFR2-altered cancer cells (e.g., NCI-H716, SNU-16, Kato III) are seeded in 96-well plates. Cells are treated with Lirafugratinib (0.1-1000 nM) for 72-96 hours. Cell viability is measured by CellTiter-Glo. FGFR2 phosphorylation and downstream signaling (p-ERK, p-AKT) are assessed by Western blot after 2-6 h treatment. Apoptosis is measured by caspase-3/7 activation or Annexin V staining.
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| Animal Protocol |
In mouse xenograft models, cancer cells are injected subcutaneously into nude or NSG mice. When tumors reach a certain size (e.g., 150-200 mm3), Lirafugratinib is administered orally daily or twice daily at 1-30 mg/kg for 2-4 weeks. Tumor volume is measured by calipers. Post-treatment, tumors are harvested for p-FGFR2, p-ERK, p-AKT, Ki67, and cleaved caspase-3 analysis.
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| ADME/Pharmacokinetics |
Lirafugratinib is orally bioavailable. Following oral administration, peak plasma concentrations are reached within 1-3 hours. It is highly plasma protein bound. The irreversible mechanism leads to prolonged target engagement. Metabolism is primarily hepatic, with a moderate to long half-life (6-12 hours). For in vitro use, solubility: DMSO ≥ 100 mg/mL.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies show a manageable safety profile. Common adverse events at therapeutic doses are mild and may include diarrhea, dry eye, and nail changes (consistent with FGFR inhibitor class effects). At higher doses, hyperphosphatemia due to off-target FGFR1 inhibition may occur. Not approved for human use.
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| References | |
| Additional Infomation |
Lirafugratinib hydrochloride is the hydrochloride form of Lirafugratinib, an orally bioavailable fibroblast growth factor receptor 2 (FGFR2) inhibitor with potential antitumor activity. After oral administration, Lirafugratinib binds to FGFR2 and inhibits its activity, thereby suppressing FGFR2-mediated signal transduction pathways. This inhibits the proliferation of FGFR2-overexpressing tumor cells. FGFR2 is a receptor tyrosine kinase upregulated in various tumor cell types and plays a crucial role in cell proliferation, migration, and survival.
Lirafugratinib (also known as RLY-4008) is an investigational drug. It has demonstrated clinical activity in phase 1/2 trials for intrahepatic cholangiocarcinoma and other FGFR2-fusion positive solid tumors. It is not yet FDA-approved. Molecular formula: C28H25ClFN7O2; molecular weight: 546.00. |
| Molecular Formula |
C28H25CLFN7O2
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|---|---|
| Molecular Weight |
545.995207548141
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| Exact Mass |
545.174
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| CAS # |
2688040-45-9
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| Related CAS # |
Lirafugratinib;2549174-42-5
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| PubChem CID |
163377372
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| Appearance |
Light brown to brown solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
39
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| Complexity |
840
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1C2=NC=NC(N)=C2C(C2C=CC(OC3=NC=CC(C)=N3)=C(F)C=2)=C1C1C=CC(NC(=O)C(=C)C)=CC=1.Cl
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| InChi Key |
HLGJPRBWELSHLI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H24FN7O2.ClH/c1-15(2)27(37)35-19-8-5-17(6-9-19)24-22(23-25(30)32-14-33-26(23)36(24)4)18-7-10-21(20(29)13-18)38-28-31-12-11-16(3)34-28;/h5-14H,1H2,2-4H3,(H,35,37)(H2,30,32,33);1H
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| Chemical Name |
N-[4-[4-amino-5-[3-fluoro-4-(4-methylpyrimidin-2-yl)oxyphenyl]-7-methylpyrrolo[2,3-d]pyrimidin-6-yl]phenyl]-2-methylprop-2-enamide;hydrochloride
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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 : ~125 mg/mL (~228.94 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 | 1.8315 mL | 9.1575 mL | 18.3150 mL | |
| 5 mM | 0.3663 mL | 1.8315 mL | 3.6630 mL | |
| 10 mM | 0.1832 mL | 0.9158 mL | 1.8315 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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