TAS-115-mesylate-TAS-115-methanesulfonate-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETAS-115 mesylateCat. No.: HY-12423ACAS No.: 1688673-09-7Synonyms: TAS-115 methanesulfonate分式: CHFNOS分量: 614.66作靶点: VEGFR; c-Met/HGFR作通路: Protein Tyrosine Kinase/RTK储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1

2、 month溶解性数据体外实验 DMSO : 75 mg/mL (122.02 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.6269 mL 8.1346 mL 16.2692 mL5 mM 0.3254 mL 1.6269 mL 3.2538 mL10 mM 0.1627 mL 0.8135 mL 1.6269 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

3、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 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.07 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.07 mM); Clear solution1/2 Master of Small Molecules 您边的抑制剂师www

4、.MedChemEBIOLOGICAL ACTIVITY物活性 TAS-115 mesylate种有效的 VEGFR 和肝细胞长因受体 (c-Met/HGFR) 的靶向激酶抑制剂，能够抑制rVEGFR2 和 rMET 的活性，IC50 值分别为 30 和 32 nM。IC50 & Target IC50: 30 nM (rVEGFR2), 32 nM (rMET) 1体外研究 TAS-115 powerfully suppresses the VEGF-dependent proliferation of HUVECs (IC50=0.019 M) as aVEGFR-targeted inh

5、ibitor and powerfully suppresses the proliferation of MET-amplified cancer cells(GI50=0.032-0.362 M) as a MET-targeted inhibitor. TAS-115 has much less toxicity in various normal celllines when compared with other VEGFR-targeted kinase inhibitors 1. Crizotinib and TAS-115 inhibit Metphosphorylation

6、and reverse erlotinib resistance and VEGF production triggered by HGF in PC-9 andHCC827 cells 2.体内研究 TAS-115 completely suppresses the progression of MET-inactivated tumor by blocking angiogenesis withouttoxicity when given every day for 6 weeks, even at a serum-saturating dose of TAS-115. TAS-115 i

7、nducesmarked tumor shrinkage and prolonges survival in MET-amplified human cancerbearing mice 1.PROTOCOLCell Assay 2 Tumor cells (8000 cells/800 mL) with or without TAS-115 (1.0 M) or erlotinib (0.3 M) in the lower Transwellcollagencoated chambers are cocultured with MRC-5 (1000 cells/300 L) cells i

8、n the upper chamber for 72hours. The upper chamber is then removed. Cell viability is measured using the MTT assay 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 The TAS-115 dose levels are set at 12.5, 50, and 200 mg/kg

9、/d. The dose level for sunitinib is set at 40mg/kg/d. Oral drug treatment is continued for 14 or 42 consecutive days for the chronic dosing in the SC-9xenograft model. During the treatment period, TV and body weight are measured twice per week. Theantitumor efficacy is assessed at the end of each st

10、udy period 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Fujita H, et al. The novel VEGF receptor/MET-targeted kinase inhibitor TAS-115 has marked in vivo antitumor properties and a favorabletolerability profile. Mol Cancer Ther. 2013 Dec;12(12):2685-96.2. Nakade J, et al. Triple inhibition of EGFR, Met, and VEGF suppresses regrowth of HGF-triggered, erlotinib-resistant lung cancerharboring an EGFR mutation. J Thorac Oncol. 2014 Jun;9(6):775-83.McePdfHeightCaution: Product has not been