| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
N‑Desethyl Sunitinib hydrochloride targets the same kinases as its parent compound Sunitinib: VEGFR‑1, VEGFR‑2, VEGFR‑3, PDGFRβ, and KIT, with Ki values of 2, 9, 17, 8, and 4 nM, respectively. It is an ATP‑competitive inhibitor that binds to the kinase ATP‑binding pocket, preventing phosphorylation and downstream signaling. This inhibition leads to anti‑angiogenic and anti‑proliferative effects.
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| ln Vitro |
Moreover, sunitinib strongly inhibits FLT-3 and Kit[1]. With a Ki of 9 nM and 8 nM, respectively, sunitinib is a strong ATP-competitive inhibitor of VEGFR2(Flk1) and PDGFRβ. Its selectivity for VEGFR2 and PDGFR is >10-fold higher than that of FGFR-1, EGFR, Cdk2, Met, IGFR-1, Abl, and src. Sunitinib suppresses VEGF-dependent VEGFR2 phosphorylation and PDGF-dependent PDGFRβ phosphorylation with IC50 values of 10 nM and 10 nM, respectively, in serum-starved NIH-3T3 cells expressing VEGFR2 or PDGFRβ. With an IC50 of 40 nM for VEGF, sunitinib prevents serum-starved HUVECs from proliferating, and an IC50 of 39 nM and 69 nM for PDGF, respectively, prevents NIH-3T3 cells overexpressing PDGFRβ or PDGFRβ from proliferating[2]. For wild-type FLT3, FLT3-ITD, and FLT3-Asp835, sunitinib suppresses phosphorylation with IC50 values of 250 nM, 50 nM, and 30 nM, respectively. Sunitinib causes apoptosis in MV4;11 and OC1-AML5 cells in a dose-dependent manner[3] and suppresses their growth with IC50 values of 8 nM and 14 nM, respectively.
In vitro, N‑Desethyl Sunitinib hydrochloride exhibits the same kinase inhibitory activity as Sunitinib. Sunitinib inhibits VEGF‑dependent VEGFR2 phosphorylation and PDGF‑dependent PDGFRβ phosphorylation with IC50 values of 10 nM each. It inhibits VEGF‑induced proliferation of HUVECs with an IC50 of 40 nM and PDGF‑induced proliferation of NIH‑3T3 cells overexpressing PDGFRβ or PDGFRα with IC50 values of 39 nM and 69 nM, respectively. |
| ln Vivo |
Sunitinib (20-80 mg/kg/day) significantly and selectively inhibits VEGFR2 or PDGFR phosphorylation and signaling in vivo, as demonstrated by its broad and strong dose-dependent anti-tumor activity against a range of tumor xenograft models, such as HT-29, A431, Colo205, H-460, SF763T, C6, A375, or MDA-MB-435. When sunitinib (80 mg/kg/day) is administered for 21 days, six out of eight mice experience complete tumor regression, with no tumor growth during the 110-day observation period following the conclusion of treatment. For cancers that do not completely regress after the first round of treatment, a second round of Sunitinib treatment is still effective. Tumor MVD is significantly reduced with sunitinib treatment, with SF763T glioma tumors reduced by approximately 40%. While the size of the tumor remains same, SU11248 therapy completely inhibits further tumor growth in luciferase-expressing PC-3M xenografts[2]. Sunitinib therapy (20 mg/kg/day) prolongs survival in the FLT3-ITD bone marrow engraftment model and greatly reduces the growth subcutaneous MV4;11 (FLT3-ITD) xenografts[3].
In vivo, Sunitinib (20‑80 mg/kg/day) exhibits broad and potent dose‑dependent anti‑tumor activity against a variety of tumor xenograft models, including HT‑29, A431, Colo205, H‑460, SF763T, C6, A375, and MDA‑MB‑435. The N‑desethyl modification improves the pharmacokinetic profile and contributes significantly to the therapeutic effects of Sunitinib in vivo. |
| Enzyme Assay |
Non‑cellular kinase assays for N‑Desethyl Sunitinib hydrochloride involve measuring its inhibitory activity against purified kinases (VEGFR‑1, ‑2, ‑3, PDGFRβ, KIT). The compound is incubated with the kinase and a peptide substrate in the presence of ATP, and the inhibition of phosphorylation is quantified to determine Ki values.
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| Cell Assay |
In vitro cellular assays for N‑Desethyl Sunitinib hydrochloride are performed using various cell lines. HUVECs are treated with the compound to assess inhibition of VEGF‑induced proliferation. NIH‑3T3 cells overexpressing PDGFRβ or PDGFRα are used to assess inhibition of PDGF‑induced proliferation. MV4;11 and OC1‑AML5 cells are used to assess inhibition of proliferation and induction of apoptosis.
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| Animal Protocol |
In vivo animal experiments for N‑Desethyl Sunitinib hydrochloride are typically conducted using the parent compound Sunitinib, as the metabolite is generated in vivo. Sunitinib (20‑80 mg/kg/day) is administered to tumor xenograft models, and tumor growth inhibition is assessed. The N‑desethyl metabolite contributes to the overall anti‑tumor activity observed with Sunitinib treatment.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties for N‑Desethyl Sunitinib hydrochloride indicate that it is the active metabolite of Sunitinib and contributes to its therapeutic effects. The compound has a molecular weight of 406.89 and a molecular formula of C20H24ClFN4O2. It is soluble in DMSO (40 mg/mL) and can be formulated for in vivo administration in 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline (2 mg/mL). It should be stored at low temperature.
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| Toxicity/Toxicokinetics |
Toxicological data for N‑Desethyl Sunitinib hydrochloride are similar to those of Sunitinib. Sunitinib has a well‑characterized safety profile from clinical use. Common adverse effects include fatigue, diarrhea, nausea, hypertension, and hand‑foot skin reaction. The hydrochloride salt form is intended for research use only and not for human consumption.
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| References |
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| Additional Infomation |
N‑Desethyl Sunitinib hydrochloride (SU‑12662 hydrochloride) is the active metabolite of Sunitinib, a potent ATP‑competitive inhibitor of VEGFR, PDGFRβ, and KIT. It has potential anti‑cancer activity and is used in oncology research to study kinase signaling and drug metabolism. It is supplied for research purposes only.
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| Molecular Formula |
C20H24CLFN4O2
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| Molecular Weight |
406.88
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| Related CAS # |
N-Desethyl Sunitinib;356068-97-8
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| Appearance |
Yellow to brown solid powder
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 :~50 mg/mL (~122.89 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.14 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (6.14 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4577 mL | 12.2886 mL | 24.5773 mL | |
| 5 mM | 0.4915 mL | 2.4577 mL | 4.9155 mL | |
| 10 mM | 0.2458 mL | 1.2289 mL | 2.4577 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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