SU14813 - PDGFR 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESU14813Cat. No.: HY-10501CAS No.: 627908-92-3分式: CHFNO分量: 442.48作靶点: PDGFR; VEGFR; c-Kit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 DMSO : 44 mg/mL (99.44 mM; N

2、eed ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.2600 mL 11.2999 mL 22.5999 mL5 mM 0.4520 mL 2.2600 mL 4.5200 mL10 mM 0.2260 mL 1.1300 mL 2.2600 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，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

3、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 (5.65 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.65 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE物活性 SU148

4、13是多靶点受体酪氨酸激酶抑制剂，抑制 VEGFR2，VEGFR1，PDGFR and KIT 的 IC50 值分别为50，2，4，15 nM。IC50 & Target VEGFR1 VEGFR2 PDGFR KIT2 nM (IC50) 50 nM (IC50) 4 nM (IC50) 15 nM (IC50)体外研究 SU14813 inhibits ligand-dependent and ligand-independent proliferation, migration, and survival ofendothelial cells and/or tumor cells ex

5、pressing these targets. SU14813 inhibits cellular ligand-dependentphosphorylation of VEGFR-2 (transfected NIH 3T3 cells), PDGFR- (transfected NIH 3T3 cells), KIT (Mo7ecells), and FLT3-internal tandem duplication (FLT3-ITD; MV4;11 cells) as well as FMS/CSF1R (transfectedNIH 3T3 cells). SU14813 inhibi

6、ts VEGFR-2, PDGFR-, and KIT phosphorylation in porcine aorta endothelialcells overexpressing these targets, with cellular IC50 values of 5.2, 9.9, and 11.2 nM, respectively. SU14813inhibits the growth of U-118MG with an IC50 of 50 to 100 nM 1.体内研究 SU14813 inhibits VEGFR-2, PDGFR-, and FLT3 phosphory

7、lation in xenograft tumors in a dose- and time-dependent fashion. The plasma concentration required for in vivo target inhibition is estimated to be 100 to200 ng/mL. Used as monotherapy, SU14813 exhibits broad and potent antitumor activity resulting inregression, growth arrest, or substantially redu

8、ces growth of various established xenografts derived fromhuman or rat tumor cell lines. Treatment in combination with docetaxel significantly enhances both theinhibition of primary tumor growth and the survival of the tumor-bearing mice compared with administration ofeither agent alone 1.PROTOCOLCel

9、l Assay 1 The effect of SU14813 on endothelial cell survival is evaluated. Passages 4 to 5 human umbilical veinendothelial cells are grown to subconfluency in EGM2 medium containing 10% FBS, endothelial cell growthsupplement, and 10 g/mL sodium heparin. The cells are seeded in 96-well plates at 10,0

10、00 per well in F12Kmedium and 10% FBS. The next day, cells are starved for 18 hours in F12K+1% FBS and then incubatedwith SU14813 in various concentrations. 45 minutes later, 20 ng/mL growth factor VEGF or basic fibroblastgrowth factor (bFGF) is introduced into the assay. Three days later, cell numb

11、ers are determined using the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mouse: SU14813 is evaluated for its efficacy and synergism in combination with the microtubule inhibi

12、torAdministration 1 docetaxel in docetaxel-resistant murine LLC model. SU14813 is administered p.o. twice daily (BID) at dosesof 10, 40, 80, or 120 mg/kg beginning on day 5 after tumor implantation. Docetaxel 40 mg/kg (mousemaximum tolerated dose) is administered i.v. thrice weekly also beginning on

13、 day 5 after tumor implantation1.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 Science. 2017 Dec 1;358(6367).2/3 Master of Small Molecules 您边的抑制剂师www.MedChemESee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Patyna S, et al. SU14813: a novel multiple receptor tyrosine kinase inhibitor with potent antiangiogenic and antitumor activity. MolCancer Ther. 2006 Jul;5(7):1774-82