Sunitinib Malate (SU 11248 Malate) is a multi-targeted receptor tyrosine kinase inhibitor with IC₅₀s of 80 nM and 2 nM for VEGFR2 and PDGFRβ, respectively^[1]. Sunitinib Malate, an ATP-competitive inhibitor, effectively inhibits autophosphorylation of Ire1α by inhibiting autophosphorylation and consequent RNase activation^[2].

Sunitinib Malate is also a good inhibitor of KIT and FLT-3^[1]. In RS4;11 cells (FLT3-WT), treatment with Sunitinib (SU11248) inhibits FLT3-WT phosphorylation in a dose-dependent manner with IC₅₀ of approximately 250 nM. In MV4;11 cells that express FLT3-ITD, Sunitinib inhibits FLT3-ITD phosphorylation in a dose-dependent manner with an IC₅₀ of 50 nM following a 2-hour treatment^[3].In biochemical assays, Sunitinib (SU11248) exhibits competitive inhibition (with regard to ATP) against Flk-1 and PDGFRβ with K_i values of 9 nM and 8 nM, respectively. Sunitinib is also a competitive, albeit less potent, inhibitor of FGFR1 tyrosine kinase activity, with a K_i value of 0.83 μM. In addition to these three structurally related split kinase domain RTKs, the activity of Sunitinib has also been evaluated against a broad panel of additional tyrosine and serine/threonine kinases. In these biochemical assays, the IC₅₀ values for Sunitinib are generally at least 10-fold higher than those for Flk-1 and PDGFR (e.g., IC₅₀values of: >10 μM for EGFR and Cdk2; 4 μM for Met; 2.4 μM for IGFR-1; 0.8 μM for Abl; and 0.6 μM for Src)^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Sunitinib Malate has very good oral bioavailability, is highly efficacious in a number of preclinical tumor models, and is well tolerated at efficacious doses^[1]. Sunitinib (80 mg/kg/day) inhibits the growth of established SF763T and Colo205 tumor xenografts in athymic mice. Sunitinib (SU11248) treatment effectively inhibits the growth of established tumor xenografts^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

532.56

C₂₆H₃₃FN₄O₇

341031-54-7

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

DMSO : ≥ 15 mg/mL (28.17 mM)

H₂O : 12.5 mg/mL (23.47 mM; ultrasonic and adjust pH to 3 with HCl)

* “≥” means soluble, but saturation unknown.

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 100 mM citrate buffer

  Solubility: 10 mg/mL (18.78 mM); Suspended solution; Need ultrasonic and adjust pH to 5 with HCl
• 2.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (4.69 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.69 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 3.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (4.69 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.69 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 4.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (4.69 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.69 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [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]. Ali MM, et al. Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response. EMBO J. 2011 Mar 2;30(5):894-905.

  [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.

  [4]. 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

Biochemical assays to determine the activity of Sunitinib against different protein kinases are performed. K_i values for SU11248 against Flk-1, PDGFRβ, and FGFR1 are determined using glutathione S-transferase-fusion proteins containing the complete cytoplasmic domain of the RTK. Cellular assays to directly determine the ability of SU11248 to inhibit ligand-dependent RTK phosphorylation or cell proliferation and mitogenic responses are performed using serum-starved cells stimulated with 40 ng/mL VEGF₁₆₅ (Flk-1/KDR), 0.5 μg/mL basic FGF (FGFR), or 50 ng/mL PDGF-AA (PDGFRα) or PDGF-BB (PDGFRβ)^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

RS4;11 and MV4;11 cell lines are starved overnight in medium containing 0.1% FBS prior to addition of SU11248 (1 nM, 5 nM, 10 nM, 25 nM, 75 nM, 100 nM, 250 nM, 500 nM) and FL (50 ng/mL; FLT3-WT cells only). Proliferation is measured after 48 hours of culture using the Alamar Blue assay in triplicate for each condition, as described by the manufacturer. Trypan blue cell viability assays are performed in parallel and yielded similar results^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mice^[2]
Female nu/nu mice (8-12 weeks old, 25 g) are used. Briefly, 3-5×10⁶ tumor cells are implanted s.c. into the hind flank region of mice on day 0. Daily treatment of tumor-bearing mice with oral administration of SU11248 as a carboxymethyl cellulose suspension or as a citrate buffered (pH 3.5) solution is initiated once the tumors reached the indicated average size. Tumor growth is evaluated based on twice-weekly measurement of tumor volume. Typically, studies are terminated when tumors in vehicle-treated animals reach an average size of 1000 mm³ or when the tumors are judged to adversely effect the well being of the animals.
Rats^[4]
Forty female Sprague-Dawley rats (200-230 g) are used. Each group consists of 5-10 animals fed ad libitum. 1×10⁴ Walker 256 cells are injected into the left abdominal mammary fat pad, under gas anesthesia (2% isoflurane). Rats are weighed daily and given Sunitinib malate (30 mg/kg) and/or Fingolimod (5 mg/kg) in olive oil by gavage. The tumors are measured with calipers. The animals are anesthetized and killed by an intracardiac injection of ketamine (50 mg/mL) before tumor ulceration. Rats are dissected to detect pulmonary, liver, kidney, or intestinal metastasis.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [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]. Ali MM, et al. Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response. EMBO J. 2011 Mar 2;30(5):894-905.

  [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.

  [4]. 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