1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAltiratinibCat. No.: HY-B0791CAS No.: 1345847-93-9Synonyms: DCC-2701分式: CHFNO分量: 510.46作靶點(diǎn): VEGFR; c-Met/HGFR; FLT3; Trk Receptor作通路: Protein Tyrosine Kinase/RTK; Neuronal Signaling儲存式: Powder -20C 3 years4C 2 yearsIn solvent -8

2、0C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 33 mg/mL (64.65 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.9590 mL 9.7951 mL 19.5902 mL5 mM 0.3918 mL 1.9590 mL 3.9180 mL10 mM 0.1959 mL 0.9795 mL 1.9590 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。BIOLOGI

3、CAL ACTIVITY物活性 Altiratinib (DCC-2701)是多靶點(diǎn)激酶抑制劑，抑制 MET，TIE2，VEGFR2，F(xiàn)LT3，Trk1，Trk2 和 Trk3 的 IC50值分別為2.7，8，9.2，9.3，0.85，4.6，0.83 nM。IC50 & Target VEGFR2 Trk1 Trk2 Trk39.2 nM (IC50) 0.85 nM (IC50) 4.6 nM (IC50) 0.93 nM (IC50)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEMET TIE2 FLT32.7 nM (IC50) 8

4、nM (IC50) 9.3 nM (IC50)體外研究 Altiratinib also inhibits MET isoforms METD1228H, MET D1228N, METY1230C, METY1230D, METY1230H,METM1250T with IC50s of 3.6, 1.3, 1.2, 0.37, 1.5 and 6 nM, respectively. Altiratinib inhibits METphosphorylation with IC50 values of 0.85 and 2.2 nM, respectively. In the U-87 gl

5、ioblastoma cell line, METand HGF are both expressed. Altiratinib blocks autocrine activation of MET phosphorylation in these cells(IC50=6.2 nM). Altiratinib potently inhibits cellular proliferation in MET-amplified EBC-1 and MKN-45 cells, aswell as TPM3-TRKA fusion KM-12 cells. Activation of MET is

6、known to increase the motility and invasivenessof cancer cells: Altiratinib inhibits HGF-induced A549 cell migration, with an IC50 of 13 nM. Altiratinib alsoinhibits FLT3-ITD mutant MV-4-11 cell proliferation with an IC50 of 12 nM 1.體內(nèi)研究 A single oral dose of 30 mg/kg Altiratinib leads to 95% inhibi

7、tion of MET phosphorylation for the entire 24-hour period. A single 10 mg/kg oral dose of Altiratinib exhibits complete inhibition of MET phosphorylationthrough 12 hours and 73% inhibition at 24 hours postdose. Altiratinib dosed at 10 mg/kg twice a day leads toa significant 90% decrease in BLI signa

8、l. Altiratinib exhibits properties amenable to oral administration andexhibits substantial bloodbrain barrier penetration, an attribute of significance for eventual treatment of braincancers and brain metastases 1.PROTOCOLCell Assay 1 Altiratinib is dispensed into assay plates. Cells are added to 96

9、-well (EBC-1, M-NFS-60, and SK-MEL-28:2,500 cells/well; MKN-45: 5,000 cells/well; MV-4-11: 10,000 cells/well) or 384-well plates (A375 and HCT-116: 625 cells/well; BT-474, KM-12, PC-3, and U-87-MG: 1,250 cells/well). Plates are incubated for 72 hours.Viable cells are quantified using resazurin using

10、 a plate reader with excitation at 540 nm and emission at 600nm 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Female nude mice are inoculated subcutaneously. On days 9 to 10, when tumor volumes reached 326Administration 1 mg on average,

11、 mice are randomly assigned to groups and dosed once orally with 0.4% HMPC, (n=3);Altiratinib at 30 mg/kg (n=21); or Altiratinib at 10 mg/kg (n=21). At specified time points, whole blood andtumors are collected. Pharmacokinetic analysis is performed. Tumor samples are processed in the Westernblot as

12、say methods 1.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) Patent. US20170349880A1.See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Smith BD, et al. Altiratinib Inhibits Tumor Growth, Invasion, Angiogenesis, and Microenvironment-Mediated DrugResistance viaBalanced Inhibition of MET, TIE2, and VEGFR2. Mol Cancer Ther. 2015 Sep;14(9):2023-34.McePdfHeightC