N-Desethyl Sunitinib (SU-12662) ( HCl) is a metabolite of Sunitinib. Sunitinib is a potent, ATP-competitive inhibitor of VEGFR, PDGFRβ and KIT, capable of inhibiting the activities of VEGFR -1, VEGFR -2, VEGFR -3, PDGFRβ and KIT with Kis of 2, 9, 17, 8 and 4 nM, respectively. .

Physicochemical Properties

Molecular Formula	C20H24CLFN4O2
Molecular Weight	406.88
Related CAS #	N-Desethyl Sunitinib;356068-97-8
Appearance	Yellow to brown solid powder
HS Tariff Code	2934.99.9001
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)

Biological Activity

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.
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].
References	[1]. 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 receptor tyrosine kinase. J Med Chem. 2003;46(7):1116-1119. [2]. 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 Cancer Res. 2003;9(1):327-337. [3]. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood. 2003;101(9):3597-3605.

Solubility Data

Solubility (In Vitro)

DMSO :~50 mg/mL (~122.89 mM)

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.