BMS-777607-BMS-817378-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBMS 777607Cat. No.: HY-12076CAS No.: 1025720-94-8Synonyms: BMS 817378分式: CHClFNO分量: 512.89作靶點(diǎn): c-Met/HGFR; TAM Receptor作通路: Protein Tyrosine Kinase/RTK儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外

2、實(shí)驗(yàn) DMSO : 39 mg/mL (76.04 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.9497 mL 9.7487 mL 19.4974 mL5 mM 0.3899 mL 1.9497 mL 3.8995 mL10 mM 0.1950 mL 0.9749 mL 1.9497 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 BMS 777607種 Me

3、t-related 抑制劑，能夠抑制 c-Met，Axl，Ron 和 Tyro3 的活性，IC50 值為 3.9nM，1.1 nM，1.8 nM 和 4.3 nM。IC50 & Target IC50: 3.9 nM (c-Met), 1.1 nM (Axl), 1.8 nM (Ron), 4.3 nM (Tyro3)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 BMS 777607 is a selective ATP-competitive Met kinase inhibitor which potently blocks t

4、heautophosphorylation of c-Met with IC50 of 20 nM in GTL-16 cell lysates, and demonstrates selectiveinhibition of proliferation in Met-driven tumor cell lines, such as GTL-16 cell line, H1993 and U87 1. BMS777607 inhibits hepatocyte growth factor (HGF)-triggered c-Met autophosphorylation with IC50 o

5、f 1 nM inPC-3 and DU145 prostate cancer cells. BMS 777607 has little effect on tumor cell growth, but exhibitsinhibitory effect on HGF-induced cell scattering in PC-3 and DU145 cells, with almost complete inhibition at0.5 M. BMS 777607 also suppresses stimulated cell migration and invasion in a dose

6、-dependent fashion(IC50 0.1 M) in both cell lines 2. Application of BMS 777607 (appr 10 M) to the highly metastatic murineKHT cells for 2 hours potently eliminates basal levels of autophosphorylated c-Met with IC50 of 10 nMwithout affecting the total c-Met, leading to dose-dependent inhibition of ph

7、osphorylation of downstreamsignaling molecules including ERK, Akt, p70S6K and S6. Treatment with BMS 777607 (appr 1 M) for 24hours potently inhibits the KHT cell scatter, motility and invasion at doses in the nanomolar range whichconsists with MET gene knockdown, and modestly affects cell proliferat

8、ion and colony formation 3.體內(nèi)研究 Oral administration of BMS 777607 (6.25-50 mg/kg) significantly reduces tumor volumes of the GTL-16human tumor xenografts in athymic mice with no observed toxicity 1. Administration of BMS 777607 (25mg/kg/day) decreases the number of KHT lung tumor nodules (28.3%), im

9、proves the morphologicalhemorrhage, and significantly impairs the metastatic phenotype in the 6-8 week-old female C3H/HeJ miceinjected with rodent fibrosarcoma KHT cells without apparent systemic toxicity compared to the controltreatment. A low dose of BMS 777607 (10 mg/kg) also offers a mild but no

10、t significant inhibition of lungnodule formation compared to the vehicle control 3.PROTOCOLCell Assay 3 KHT cells are exposed to serial dilution of BMS 777607 for 96 hours, then the MTT assay and trypan blueexclusion are used for the determination of cell proliferation and cell death, respectively.

11、KHT cell coloniesare incubated with BMS 777607 for 24 hours and then stained with crystal violet (0.1%) and photographedfor the assessment of cell scattering. 2 mm scratch on the confluent KHT cell monolayer is made using asterilized 1 mL pipette tip followed by treated with BMS 777607 for 24 hours,

12、 then the number of cells thathave migrated into the denuded area is counted on 4 random fields for the evaluation of cell migration. Forthe examination of cell invasion, the commercial transwell inserts (8 M pore membrane) pre-loaded withMatrigel are incubated with serum-free medium in the presence

13、 or absence of BMS 777607 at 37C for 2hours to allow rehydration of Matrigel. Then cells suspended in serum-free medium are loaded onto the topchamber (5103/insert) and complete medium (containing 10% FBS) is used in the lower chamber as achemoattractant. After incubation for 24 hours, the Matrigel

14、is removed and the inserts are stained withcrystal violet. Invaded cells on the underside of the filter are photographed and counted.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal The pharemacokinetics of BMS 777607 are characterized in male Bal

15、b/C mice. Two groups of animals (N=6Administration 1 per group, 20-25 g) are fasted overnight and receive BMS 777607 either as an intravenous (IV) bolus dose (5mg/kg) via the tail vein or by gavage (10 mg/kg). The mice are fed 6 h after dosing. Blood samples (appr 0.2mL) are obtained by retro-orbita

16、l bleeding at 0.05 (or 0.25 for oral), 0.5, 1, 3, 6, 8 and 24 h post dose. Withineach group, half of the animals are bled at 0.05 (or 0.25 for oral), 1, 6 and 24 h, the other half are bled at 0.5,2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3, and 8 h, resulting in a composite pharmacokinetic pr

17、ofile (3 mice per time point). Blood samples areallowed to coagulate and centrifuged at 4C (1500-2000 g) to obtain serum. Serum samples are stored atappr 20C until analysis by LC/MS/MS.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Sci Tran

18、sl Med. 2018 Jul 18;10(450). pii: eaaq1093. Exp Cell Res. 2019 Apr. Taiwan J Obstet Gyne. 2019 Jan. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Schroeder GM, et al. Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily.