| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
VEGFR-2 (KDR), PDGFR-beta, and c-KIT. Sunitinib D10 acts as an ATP-competitive inhibitor that binds to the ATP-binding pocket of multiple receptor tyrosine kinases. It potently inhibits the kinase activity of VEGFR2 (KDR), PDGFRbeta, and c-KIT with IC50s of 80 nM, 2 nM, and 100 nM, respectively. It also inhibits other RTKs including FLT3, RET, CSF-1R, and FGFRs. By blocking these RTKs, it inhibits angiogenesis, tumor cell proliferation, and metastasis.
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| ln Vitro |
Sunitinib inhibits VEGFR2 and PDGFRbeta kinase activity in cell-free assays with IC50s of 80 nM and 2 nM, respectively. It potently inhibits VEGF-stimulated HUVEC proliferation (IC50 = 10 nM) and PDGF-stimulated pericytes. Sunitinib also inhibits autophosphorylation of Ire1alpha (a sensor of ER stress) by blocking its RNase activity. The D10-labeled form has equivalent biochemical activity.
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| ln Vivo |
In murine xenograft models (e.g., HT-29 colon carcinoma, A431 epidermoid carcinoma, A549 NSCLC, or RENAL renal cell carcinoma), oral Sunitinib (20-80 mg/kg daily) inhibits tumor growth by 50-90% (TGI) and reduces tumor microvessel density (MVD). In a rat model of rheumatoid arthritis (adjuvant-induced arthritis), sunitinib (30 mg/kg/day) reduces joint inflammation and bone erosion.
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| Enzyme Assay |
Cell-free kinase inhibition assays are performed using recombinant human VEGFR2 (KDR) or PDGFRbeta kinases (1-5 nM) in 50 mM HEPES buffer (pH 7.5) containing 10 mM MgCl2, 2 mM MnCl2, 1 mM DTT, 0.01% BSA, and 10 uM ATP. Varying concentrations of Sunitinib D10 (0.1-1000 nM) are added. The reaction is initiated by adding a biotinylated peptide substrate. After 60 min at 30degC, phosphorylation is detected by TR-FRET (time-resolved fluorescence resonance energy transfer). IC50 values are calculated.
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| Cell Assay |
Human umbilical vein endothelial cells (HUVECs) are cultured in EBM-2 medium supplemented with EGM-2 bullet kit. Cells are seeded in 96-well plates (5-10 × 103 cells/well) in medium containing 0.5% FBS. After 24 h, varying concentrations of Sunitinib D10 (1-1000 nM) are added, followed by stimulation with VEGF (10 ng/mL) or PDGF (10 ng/mL) for 72 h. Cell proliferation is measured using the CellTiter-Glo luminescent assay. The IC50 for inhibition of VEGF- or PDGF-stimulated proliferation is calculated.
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| Animal Protocol |
Female athymic nude mice (6-8 weeks) bearing subcutaneous HT-29 or A431 xenografts (tumor volume 150-250 mm3) are randomized (n=8-10). Sunitinib (40-80 mg/kg) or vehicle (0.5% carboxymethylcellulose) is administered orally once daily for 14-28 days. Tumor volumes are measured twice weekly. At termination, tumors are excised and weighed, and vascular density is assessed by CD31 immunohistochemistry. Pharmacokinetic blood samples are collected at multiple time points, and sunitinib concentrations are quantified by LC-MS/MS using Sunitinib D10 as the internal standard.
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| ADME/Pharmacokinetics |
Sunitinib D10 is used as an internal standard (IS) for LC-MS/MS quantification. Sunitinib has an oral bioavailability of ~60-70%, a terminal half-life of 40-60 h, and is highly protein bound (>95%). It is primarily metabolized by CYP3A4 to its equipotent primary metabolite, N-desethyl sunitinib (SU12662), which has a similar half-life and contributes to overall activity. Both parent and metabolite accumulate in plasma with repeated daily dosing.
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| Toxicity/Toxicokinetics |
The D10-labeled compound is not for human use. Sunitinib has a boxed warning for hepatotoxicity (liver injury/failure) and should be permanently discontinued if grade 3-4 LFT elevations occur. Common AEs (≥30%): fatigue, diarrhea, nausea, vomiting, stomatitis, hand-foot skin reaction (HFSR), rash, hypertension, hypothyroidism, and yellow skin discoloration (reversible). Also causes myelosuppression (neutropenia, thrombocytopenia).
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| References |
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| Additional Infomation |
Sunitinib (Sutent) was FDA-approved in 2006 for advanced renal cell carcinoma (RCC), imatinib-resistant gastrointestinal stromal tumors (GIST), and pancreatic neuroendocrine tumors (pNET). Sunitinib D10 is a research internal standard used in bioanalytical method validation, LC-MS/MS-based pharmacokinetic studies, therapeutic drug monitoring (TDM), and drug-drug interaction studies, particularly with CYP3A4 modulators.
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| Molecular Formula |
C22H17D10N4O2F
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|---|---|
| Molecular Weight |
408.535
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| Exact Mass |
408.275
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| CAS # |
1126721-82-1
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| Related CAS # |
Sunitinib;557795-19-4
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| PubChem CID |
25214491
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| Appearance |
White to yellow solid powder
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| LogP |
3.994
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
29
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| Complexity |
636
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[2H]C([2H])([2H])C([2H])([2H])N(CCNC(=O)C1=C(NC(=C1C)/C=C\2/C3=C(C=CC(=C3)F)NC2=O)C)C([2H])([2H])C([2H])([2H])[2H]
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| InChi Key |
WINHZLLDWRZWRT-BLSNYXODSA-N
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| InChi Code |
InChI=1S/C22H27FN4O2/c1-5-27(6-2)10-9-24-22(29)20-13(3)19(25-14(20)4)12-17-16-11-15(23)7-8-18(16)26-21(17)28/h7-8,11-12,25H,5-6,9-10H2,1-4H3,(H,24,29)(H,26,28)/b17-12-/i1D3,2D3,5D2,6D2
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| Chemical Name |
N-[2-[bis(1,1,2,2,2-pentadeuterioethyl)amino]ethyl]-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-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 | 2.4477 mL | 12.2387 mL | 24.4774 mL | |
| 5 mM | 0.4895 mL | 2.4477 mL | 4.8955 mL | |
| 10 mM | 0.2448 mL | 1.2239 mL | 2.4477 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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