| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Lenvatinib targets multiple receptor tyrosine kinases including vascular endothelial growth factor receptors 1-3 (VEGFR1-3), fibroblast growth factor receptors 1-4 (FGFR1-4), platelet-derived growth factor receptor (PDGFR), KIT, and RET.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[1].
Lenvatinib shows potent antitumor activities by simultaneously blocking multiple pro-angiogenic pathways. In vitro studies demonstrate concentration-dependent inhibition of endothelial cell proliferation and tube formation. |
| ln Vivo |
Lenvatinib demonstrates significant efficacy in various cancer models including medullary thyroid cancer, hepatocellular carcinoma, and renal cell carcinoma. In vivo studies have confirmed its ability to inhibit angiogenesis and tumor growth, leading to clinical approval.
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| Enzyme Assay |
Non-cell tyrosine kinase activity assays are performed using recombinant human VEGFR2 or FGFR1 kinase domains in 96-well plates. The reaction buffer contains 50 mM HEPES (pH 7.5), 10 mM MgCl2, 2 mM MnCl2, 1 mM DTT, and 0.01% Tween-20. Lenvatinib-d4 is added at concentrations from 0.1 nM to 10 uM, followed by addition of 10 uM ATP and a biotinylated peptide substrate. After incubation at 30degC for 60 minutes, the reaction is terminated with EDTA. Streptavidin-conjugated donor beads and anti-phosphotyrosine acceptor beads are added for TR-FRET detection. The signal is measured on a plate reader with excitation/emission wavelengths of 340/615 nm, and IC50 values are calculated from the dose-response curves.
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| Cell Assay |
Cellular assays are performed using human umbilical vein endothelial cells (HUVECs) or cancer cell lines such as HepG2 (hepatocellular carcinoma), K1 (thyroid cancer), or ACHN (renal carcinoma). For proliferation assays, 5,000-10,000 cells/well are seeded in 96-well plates and treated with Lenvatinib-d4 at concentrations of 0.001-10 uM for 72 hours. Cell viability is measured using CellTiter-Glo or MTS assays. For angiogenesis assays, HUVECs are seeded on Matrigel-coated plates and tube formation is assessed after 6-8 hours of treatment. Migration is evaluated using scratch wound healing assays or Boyden chamber assays (8 microm pore size, 4-hour migration). Apoptosis is assessed by caspase-3/7 activity assay or annexin V/PI staining followed by flow cytometry.
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| Animal Protocol |
In vivo efficacy studies utilize various xenograft models. Female athymic nude mice (6-8 weeks old) are subcutaneously implanted with 5×10⁶ tumor cells (e.g., HepG2, K1, or 786-O cells). When tumors reach 150-200 mm3, mice are randomized into treatment groups (n=8-10 per group). Lenvatinib-d4 is administered orally at doses of 10-30 mg/kg once daily for 14-28 days. Tumor volumes are measured twice weekly using calipers (V = length × width2 × 0.5). Body weight and clinical signs are monitored daily. At study endpoint, tumors are excised, weighed, and processed for immunohistochemistry staining for CD31 (endothelial marker), Ki-67 (proliferation), and TUNEL (apoptosis). Plasma levels of angiogenic factors (VEGF, FGF) may also be measured by ELISA.
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| ADME/Pharmacokinetics |
In humans, lenvatinib is rapidly absorbed from the gastrointestinal tract with an observed tmax typically between 1 and 4 hours. Food intake prolongs tmax to 3-7 hours. Oral clearance ranges from 4.2 to 7.1 L/h for doses between 0.8 and 32 mg. The terminal elimination half-life is approximately 28 hours in humans, allowing once-daily dosing. Lenvatinib is highly protein bound (>98%) primarily to albumin. Metabolism occurs mainly via CYP3A4, producing pharmacologically active metabolites. The deuterated form is used as an internal standard for LC-MS/MS quantification.
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| Toxicity/Toxicokinetics |
In clinical use, lenvatinib is associated with several adverse effects including hypertension (occurring in >70% of patients), fatigue, diarrhea, decreased appetite, nausea, weight loss, and palmar-plantar erythrodysesthesia. More serious toxicities include cardiac dysfunction, hepatic toxicity (elevated ALT/AST), renal impairment, and gastrointestinal perforation. The drug carries warnings for arterial thromboembolic events and hemorrhage. Dose reduction or interruption is required for management of severe toxicity. The LD50 in animals has not been determined for clinical safety reasons, but toxicological studies show dose-dependent effects on multiple organ systems.
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| References |
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| Additional Infomation |
Lenvatinib has received regulatory approval from the FDA and EMA for the treatment of advanced or metastatic thyroid cancer (2015), unresectable hepatocellular carcinoma (2018), advanced renal cell carcinoma in combination with everolimus or pembrolizumab (2016/2021), and advanced endometrial carcinoma in combination with pembrolizumab (2019). The recommended dose varies by indication and patient weight (e.g., 24 mg for thyroid cancer, 12 mg or 8 mg for HCC based on body weight). Lenvatinib-d4 is used exclusively as an internal standard for pharmacokinetic studies and bioanalysis. Phase II and III clinical trials have established lenvatinib as a standard-of-care for multiple cancer types.
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| Molecular Formula |
C21H15D4CLN4O4
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|---|---|
| Molecular Weight |
430.88
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| Exact Mass |
430.135
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| CAS # |
2264050-65-7
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| Related CAS # |
Lenvatinib;417716-92-8
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| PubChem CID |
162640490
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| Appearance |
Off-white to pink solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
634
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C1(C(C1([2H])[2H])NC(=O)NC2=C(C=C(C=C2)OC3=C4C=C(C(=CC4=NC=C3)OC)C(=O)N)Cl)[2H]
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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 | 2.3208 mL | 11.6042 mL | 23.2083 mL | |
| 5 mM | 0.4642 mL | 2.3208 mL | 4.6417 mL | |
| 10 mM | 0.2321 mL | 1.1604 mL | 2.3208 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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