| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Fruquintinib-d6, as a deuterated tracer, does not have an intrinsic therapeutic target but is used for analytical quantification. The unlabeled fruquintinib targets vascular endothelial growth factor receptors 1, 2, and 3 (VEGFR1/2/3), which are receptor tyrosine kinases (RTKs) expressed on endothelial cells. VEGFR2 is the primary mediator of angiogenesis (new blood vessel formation) in tumors, while VEGFR1 and VEGFR3 modulate other aspects of vascular biology. By potently inhibiting VEGFRs (especially VEGFR2 with an IC50 of 0.35 nM), fruquintinib blocks VEGF-induced endothelial cell proliferation, migration, and tube formation, thereby suppressing tumor angiogenesis and tumor growth. It operates within the angiogenesis and receptor tyrosine kinase pathways. [15L4-L8][15L15-L19]
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| ln Vitro |
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Studies involving the human use of drugs labeled with deuterium suggest that these compounds may offer some advantages when compared with their nondeuterated counterparts. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs. Deutetrabenazine is the first deuterated drug to receive Food and Drug Administration approval. This deuterated form of the drug tetrabenazine is indicated for the treatment of chorea associated with Huntington's disease as well as tardive dyskinesia. Ongoing clinical trials suggest that a number of other deuterated compounds are being evaluated for the treatment of human diseases and not merely as research tools.
In vitro, fruquintinib (the non-deuterated compound) potently inhibits VEGFR2 kinase activity with an IC50 of 0.35 nM in cell-free enzyme assays. It also inhibits VEGFR1 (33 nM) and VEGFR3 (35 nM). In cell-based assays (e.g., HUVECs), fruquintinib at 1-100 nM inhibits VEGF-induced endothelial cell proliferation (IC50 ~1-10 nM), migration (scratch assay), and tube formation (Matrigel assay). It also inhibits phosphorylation of VEGFR2 and downstream signaling (ERK, AKT) in endothelial cells. No significant cytotoxicity is observed in non-endothelial cells up to 10 uM. DMSO vehicle control (≤0.1%). Fruquintinib-d6 is not used for activity assays; it is an analytical standard. [15L4-L8][15L15-L19] |
| ln Vivo |
Deuterated compounds may, in some cases, offer advantages over nondeuterated forms, often through alterations in clearance. Deuteration may also redirect metabolic pathways in directions that reduce toxicities. The approval of additional deuterated compounds may soon follow. Clinicians will need to be familiar with the dosing, efficacy, potential side effects, and unique metabolic profiles of these new entities.
In vivo, fruquintinib (non-deuterated) is approved in China (Elunate®) for the treatment of metastatic colorectal cancer (mCRC). In xenograft models, oral administration of fruquintinib at 1-10 mg/kg once daily for 2-4 weeks significantly inhibits tumor growth (TGI 50-80%) in various models (colon, lung, gastric, breast). It reduces tumor microvessel density (CD31 immunohistochemistry) and inhibits VEGF-driven angiogenesis. The compound is well-tolerated at efficacious doses. Fruquintinib-d6 is not used for efficacy studies; it is an internal standard for PK studies. For research use only. [15L4-L8][15L15-L19] |
| Enzyme Assay |
Not applicable. Fruquintinib-d6 is an analytical internal standard, not used for enzyme/receptor binding assays. For analytical quality control, a standard LC-MS/MS method is used: dissolve fruquintinib-d6 in methanol or acetonitrile to prepare a 1 mg/mL stock. Dilute to working concentrations of 0.1-100 ng/mL. Add a fixed amount of fruquintinib-d6 (e.g., 10 ng/mL) as internal standard to each calibration standard and biological sample. Process samples by protein precipitation (e.g., with acetonitrile), centrifuge, and inject onto C18 HPLC column. Mobile phase: 0.1% formic acid in water (A) and acetonitrile (B). Gradient: 0-2 min: 20% B, 2-5 min: 20-80% B, 5-7 min: 80% B. Flow rate 0.3 mL/min. MS detection in positive ESI mode: fruquintinib m/z 387.4 → 355.3, fruquintinib-d6 m/z 393.4 → 361.3 (mass shift of +6 Da). Quantify by peak area ratio. [15L4-L8]
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| Cell Assay |
Not applicable. Fruquintinib-d6 is an analytical internal standard, not used for cell-based assays. For cytotoxicity studies of fruquintinib, HUVEC cells are used. Seed cells in 96-well plates (5×103 cells/well) in EBM-2 medium with 2% FBS and growth factors. Treat with fruquintinib at 0.01-1000 nM for 48-72 h. Measure viability by MTT or CellTiter-Glo. For tube formation assay, seed HUVECs on Matrigel-coated plates, treat with fruquintinib (0.1-100 nM), and quantify tube length after 6-18 h. The non-deuterated compound shows IC50 of 1-10 nM. DMSO ≤0.1%. [15L4-L8]
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| Animal Protocol |
For in vivo PK studies using fruquintinib-d6 as internal standard, male Sprague-Dawley rats (200-250 g, n=3-5/time point) are dosed orally with fruquintinib (non-deuterated) at 1-10 mg/kg. Collect blood at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 h post-dose. Plasma is separated by centrifugation. Add fruquintinib-d6 (10 ng/mL) as internal standard to each plasma sample. Extract with acetonitrile, centrifuge, and analyze by LC-MS/MS as described above. Construct calibration curve (1-1000 ng/mL) using peak area ratios. The internal standard corrects for matrix effects and extraction recovery. [15L4-L8]
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| ADME/Pharmacokinetics |
Fruquintinib-d6 (MW 399.43) is a deuterated analog. PK parameters are from the unlabeled fruquintinib. In rats and humans, fruquintinib is orally bioavailable (F% ~50-70%). In humans, after oral administration, Tmax is 2-4 h, terminal half-life (t½) is 20-30 h, volume of distribution (Vd) is moderate (~200-400 L), clearance (CL) is low (~10-20 L/h). It is highly protein bound (>90%). The compound is metabolized primarily by CYP3A4. Fruquintinib-d6 is used as an internal standard, not for PK studies of the deuterated compound. Storage: powder at -20degC for 3 years; in solvent at -80degC for 1 year. [15L4-L8]
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| Toxicity/Toxicokinetics |
No formal toxicity data are available for fruquintinib-d6 as it is an analytical standard used in trace amounts. The unlabeled fruquintinib is an approved drug with known safety profile: common adverse events include hypertension (most common, 40-60%), hand-foot skin reaction (20-30%), diarrhea, fatigue, and proteinuria. Serious adverse events include bleeding (e.g., gastrointestinal hemorrhage) and thrombosis. Hepatotoxicity (elevated ALT/AST) is also observed. The deuterated form is not expected to have a different toxicity profile. Standard laboratory safety precautions: avoid inhalation, ingestion, skin/eye contact; use PPE (gloves, lab coat); work in a fume hood. For research use only-not for human use. [15L4-L8][15L15-L19]
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| Additional Infomation |
CAS: 2978508-76-6. Molecular formula: C21H13D6N3O5 (based on fruquintinib structure), molecular weight: 399.43. Purity: 99.5% by HPLC. Isotopic purity: >98% deuterium. Synonyms: Fruquintinib-d6, HMPL-013-d6. Appearance: solid powder. Solubility: DMSO. Storage: -20degC, protect from light. Use: stable isotope-labeled internal standard for LC-MS/MS quantification of fruquintinib. Research areas: oncology, angiogenesis, pharmacokinetics. Not for human use. For research only. [15L4-L8][15L15-L19]
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| Molecular Formula |
C21H13D6N3O5
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|---|---|
| Molecular Weight |
399.43
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| Exact Mass |
399.17
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| CAS # |
2978508-76-6
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| Related CAS # |
Fruquintinib; 1194506-26-7
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| PubChem CID |
178201539
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
579
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])([2H])OC1=C(C=C2C(=C1)C(=NC=N2)OC3=CC4=C(C=C3)C(=C(O4)C)C(=O)NC)OC([2H])([2H])[2H]
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| InChi Key |
BALLNEJQLSTPIO-LIJFRPJRSA-N
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| InChi Code |
InChI=1S/C21H19N3O5/c1-11-19(20(25)22-2)13-6-5-12(7-16(13)28-11)29-21-14-8-17(26-3)18(27-4)9-15(14)23-10-24-21/h5-10H,1-4H3,(H,22,25)/i3D3,4D3
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| Chemical Name |
6-[6,7-bis(trideuteriomethoxy)quinazolin-4-yl]oxy-N,2-dimethyl-1-benzofuran-3-carboxamide
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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 | 2.5036 mL | 12.5178 mL | 25.0357 mL | |
| 5 mM | 0.5007 mL | 2.5036 mL | 5.0071 mL | |
| 10 mM | 0.2504 mL | 1.2518 mL | 2.5036 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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