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

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESunitinibCat. No.: HY-10255ACAS No.: 557795-19-4Synonyms: SU 11248分式: CHFNO分量: 398.47作靶点: VEGFR; PDGFR; Autophagy; Mitophagy作通路: Protein Tyrosine Kinase/RTK; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20

2、C 1 month溶解性数据体外实验 DMSO : 25 mg/mL (62.74 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.5096 mL 12.5480 mL 25.0960 mL5 mM 0.5019 mL 2.5096 mL 5.0192 mL10 mM 0.2510 mL 1.2548 mL 2.5096 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

3、先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，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: 1.11 mg/mL (2.79 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 1.11 mg/mL (2.79 mM); Clear solution1/3 Master of Sm

4、all Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 Sunitinib (SU 11248)种多靶点受体酪氨酸激酶抑制剂，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 Malate is also a good inhibitor of KIT and FLT-3 1. In biochemical assays, Sunitinib (SU11248)exhibits co

5、mpetitive 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 activity,with a Ki value of 0.83 M. In addition to these three structurally related split kinase dom

6、ain 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 generally at least 10-fold higher thanthose for Flk-1 and PDGFR (e.g., IC50values of: 10 M for EGFR and

7、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 IC50 of approximately 250 nM. InMV4;11 cells that express FLT3-ITD, Sunitinib inhibits FLT3-ITD phos

8、phorylation 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 tumormodels, and is well tolerated at efficacious doses 1. Sunitinib (80 mg/kg/day) inhibits the growt

9、h 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 of VEGFR,PDGFR, FGFR, and is used in the treatment of advanced renal cell carcinoma and gastrointestin

10、al 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.PROTOCOLCell Assay 3 RS4;11 and MV4;11 cell lines are starved overnight in medium containing 0.1% FBS prior to

11、addition ofSunitinib (1 nM, 5 nM, 10 nM, 25 nM, 75 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 ar

12、e performed in parallel andyielded similar results 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 grams) are used. Briefly, 3-5106 tumor cells are implanted s.c. intothe hind flank

13、region of mice on day 0. Daily treatment of tumor-bearing mice with oral administration ofSunitinib as a carboxymethyl cellulose suspension or as a citrate buffered (pH 3.5) solution is initiated oncethe tumors reached the indicated average size. Tumor growth is evaluated based on twice-weeklymeasur

14、ement of tumor volume. Typically, studies are terminated when tumors in vehicle-treated animalsreach an average size of 1000 mm3 or when the tumors are judged to adversely effect the well being of the2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEanimals.Rats 4Adult male Wistar rats (325-349 g) ar

15、e used. To validate the ability of the time-lapse imaging method toevaluate the anti-angiogenic effects for a given drug treatment, two drug studies are conducted. In the firststudy, mesenteric windows are harvested from adult male Wistar rats and cultured for 3 days according tothe two experimental

16、 groups: 1) 10% serum (n=8 tissues from 4 rats), and 2) 10% serum+Sunitinib (5 M;n=8 tissues from 4 rats).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. 2018 Jul 30;8(15):426

17、2-4278. 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-carboxylic acid (2-d

18、iethylaminoethyl)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 AM, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood. 2003 May1;101(9):3597-605.4. Azimi MS, et al. An ex vivo model for anti-angiog