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N-Desethyl Sunitinib (SU-11662) is a major metabolite of sunitinib which is a potent, ATP-competitive VEGFR, PDGFRβ and KIT inhibitor with Kis of 2, 9, 17, 8 and 4 nM for VEGFR -1, -2, -3, PDGFRβ and KIT, respectively.
| ln Vitro |
Moreover, sunitinib efficiently inhibits FLT-3 and Kit[1]. With a Ki of 8 nM for PDGFRβ and 9 nM for VEGFR2 (Flk1), sunitinib is a strong ATP competitive inhibitor. Compared to FGFR-1, EGFR, Cdk2, Met, and IGFR, it is ten times more selective for VEGFR2 and PDGFR. above. 1. Src and Abl. 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 HUVEC from proliferating, and with an IC50 of 39 nM and 69 nM for PDGF, it prevents NIH-3T3 cells overexpressing PDGFRβ or PDGFRβ from proliferating [2]. For wild-type FLT3, FLT3-ITD, and FLT3-Asp835, sunitinib inhibits 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 and suppresses their growth with IC50 values of 8 nM and 14 nM, respectively [3].
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| ln Vivo |
Across a variety of tumor xenograft models, such as HT-29, A431, Colo205, H-460, SF763T, C6, A375, or MDA-dependent antitumor activity of MB-435, sunitinib (20–80 mg/kg/day) demonstrates a broad and effective dosing range that is consistent with a significant and selective inhibition of VEGFR2 or PDGFR phosphorylation and signaling in vivo. In six out of eight mice, sunitinib (80 mg/kg/day) for 21 days led to total tumor shrinkage; no tumor regrowth occurred over the 110-day observation period following the conclusion of treatment. For tumours that did not fully regress during the first round of treatment, a second round of sunitinib remains effective. Treatment with sunitinib greatly decreased tumor MVD, with SF763T glioma tumors showing a 40% reduction. Although there was no decrease in tumor size, SU11248 therapy totally prevented further tumor growth in luciferase-expressing PC-3M xenografts [2]. In the FLT3-ITD bone marrow transplant paradigm, sunitinib therapy (20 mg/kg/day) effectively decreased the growth of subcutaneous MV4;11 (FLT3-ITD) xenografts and extended survival [3].
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| References |
[1]. Sun L, et al. Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor r
[2]. Mendel DB, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Can [3]. O'Farrell AM, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood. 2003 May 1;101(9):3597-605. Epub 2003 Jan 16 |
| Molecular Formula |
C₂₀H₂₃FN₄O₂
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|---|---|
| Molecular Weight |
370.42
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| CAS # |
356068-97-8
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| Related CAS # |
N-Desethyl Sunitinib-d5;1217247-62-5;N-Desethyl Sunitinib hydrochloride
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| SMILES |
O=C1NC2=CC=C(F)C=C2/C1=C/C3=C(C)C(C(NCCNCC)=O)=C(C)N3
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| Synonyms |
SU-11662SU11662SU 11662
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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 : ~6.25 mg/mL (~16.87 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 corn oil and mix evenly. Solubility in Formulation 2: ≥ 0.62 mg/mL (1.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 6.2 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. View More
Solubility in Formulation 3: 0.62 mg/mL (1.67 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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6996 mL | 13.4982 mL | 26.9964 mL | |
| 5 mM | 0.5399 mL | 2.6996 mL | 5.3993 mL | |
| 10 mM | 0.2700 mL | 1.3498 mL | 2.6996 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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