Sunitinib-Malate-SU-11248-Malate-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESunitinib MalateCat. No.: HY-10255CAS No.: 341031-54-7Synonyms: SU 11248 (Malate)分式: CHFNO分量: 532.56作靶点: PDGFR; VEGFR作通路: Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验

2、 DMSO : 15 mg/mL (28.17 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.8777 mL 9.3886 mL 18.7772 mL5 mM 0.3755 mL 1.8777 mL 3.7554 mL10 mM 0.1878 mL 0.9389 mL 1.8777 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液

3、，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.69 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.69 mM); Clear solution1/4 Master of

4、 Small Molecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.69 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Sunitinib Malate (SU 11248 Malate)种有效的酪氨酸激酶抑制剂， 抑制 VEGFR2 和 PDGFR 的 IC50 分别为 80 nM 和 2 nM。IC50 & Target VEGFR2 PDGFR80 nM (IC50) 2 nM (IC50)体外研究 Sunitinib Mala

5、te is also a good inhibitor of KIT and FLT-3 1. In biochemical assays, Sunitinib (SU11248)exhibits competitive inhibition (with regard to ATP) against Flk-1 and PDGFR with Ki values of 9 nM and 8nM, respectively. Sunitinib is also a competitive, albeit less potent, inhibitor of FGFR1 tyrosine kinase

6、 activity,with a Ki value of 0.83 M. In addition to these three structurally related split kinase domain RTKs, the activityof Sunitinib has also been evaluated against a broad panel of additional tyrosine and serine/threoninekinases. In these biochemical assays, the IC50 values for Sunitinib are gen

7、erally at least 10-fold higher thanthose for Flk-1 and PDGFR (e.g., IC50values of: 10 M for EGFR and Cdk2; 4 M for Met; 2.4 M for IGFR-1; 0.8 M for Abl; and 0.6 M for Src) 2. In RS4;11 cells (FLT3-WT), treatment with Sunitinib (SU11248)inhibits FLT3-WT phosphorylation in a dose-dependent manner with

8、 IC50 of approximately 250 nM. InMV4;11 cells that express FLT3-ITD, Sunitinib inhibits FLT3-ITD phosphorylation in a dose-dependentmanner with an IC50 of 50 nM following a 2-hour treatment 3.体内研究 Sunitinib Malate has very good oral bioavailability, is highly efficacious in a number of preclinical t

9、umormodels, and is well tolerated at efficacious doses 1. Sunitinib (80 mg/kg/day) inhibits the growth ofestablished SF763T and Colo205 tumor xenografts in athymic mice. Sunitinib (SU11248) treatmenteffectively inhibits the growth of established tumor xenografts 2. Sunitinib malate is an inhibitor o

10、f VEGFR,PDGFR, FGFR, and is used in the treatment of advanced renal cell carcinoma and gastrointestinal stromaltumors. Sunitinib malate-treated rats display much lower levels of tumor growth than untreated rats, and theirtumors have much smaller necrotic areas and lower vascular density 4.PROTOCOLKi

11、nase Assay 2 Biochemical assays to determine the activity of Sunitinib against different protein kinases are performed. Kivalues for SU11248 against Flk-1, PDGFR, and FGFR1 are determined using glutathione S-transferase-fusion proteins containing the complete cytoplasmic domain of the RTK. Cellular

12、assays to directly determinethe ability of SU11248 to inhibit ligand-dependent RTK phosphorylation or cell proliferation and mitogenicresponses are performed using serum-starved cells stimulated with 40 ng/mL VEGF165 (Flk-1/KDR), 0.5 g/mL basic FGF (FGFR), or 50 ng/mL PDGF-AA (PDGFR) or PDGF-BB (PDG

13、FR) 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 3 RS4;11 and MV4;11 cell lines are starved overnight in medium containing 0.1% FBS prior to addition of2/4 Master of Small Molecules 您边的抑制剂师www.MedChemESU11248 (1 nM, 5 nM, 10 nM, 25 nM, 7

14、5 nM, 100 nM, 250 nM, 500 nM) and FL (50 ng/mL; FLT3-WT cellsonly). Proliferation is measured after 48 hours of culture using the Alamar Blue assay in triplicate for eachcondition, as described by the manufacturer. Trypan blue cell viability assays are performed in parallel andyielded similar result

15、s 3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 24 Female nu/nu mice (8-12 weeks old, 25 g) are used. Briefly, 3-5106 tumor cells are implanted s.c. into thehind flank region of mice on day 0. Daily treatment of tumor-bea

16、ring mice with oral administration of SU11248as a carboxymethyl cellulose suspension or as a citrate buffered (pH 3.5) solution is initiated once the tumorsreached the indicated average size. Tumor growth is evaluated based on twice-weekly measurement oftumor volume. Typically, studies are terminate

17、d when tumors in vehicle-treated animals reach an averagesize of 1000 mm3 or when the tumors are judged to adversely effect the well being of the animals.Rats 4Forty female Sprague-Dawley rats (200-230 g) are used. Each group consists of 5-10 animals fed ad libitum.1104 Walker 256 cells are injected

18、 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) inolive oil by gavage. The tumors are measured with calipers. The animals are anesthetized and killed by anintracardiac injection of

19、 ketamine (50 mg/mL) before tumor ulceration. Rats are dissected to detectpulmonary, liver, kidney, or intestinal metastasis.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Theranostics. 20

20、18 Jul 30;8(15):4262-4278. EBioMedicine. 2018 Nov;37:344-355. Cancer Lett. 2019 Apr 10;447:105-114. J Med Chem. 2019 Jun.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Sun L, et al. Discovery of 5-5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl-2,4- dimethyl-1H-pyrrole-3-c

21、arboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor r2. Mendel DB, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor andplatelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Can3. OFarrell A