Amuvatinib-MP470-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAmuvatinibCat. No.: HY-10206CAS No.: 850879-09-3Synonyms: MP470; HPK 56分式: CHNOS分量: 447.51作靶點: c-Kit; PDGFR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)體外實驗 DMSO : 50

2、 mg/mL (111.73 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.59 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Amuvatinib (MP470)種多靶點受體酪氨酸激酶抑制劑，抑制 c-Kit (D816V)，c-Kit (D816H)，c-Kit(V560G)，c-Kit (V654A)，PDGFR (D842V)，PD

3、GFR (V561D)，IC50 分別為 950 nM，10 nM，34nM，127 nM，81 nM 和 40 nM 1。具有抗腫瘤活性 2。IC50 & Target PDGFRV561D PDGFRD842V c-KitD816H c-KitV560G40 nM (IC50) 81 nM (IC50) 10 nM (IC50) 34 nM (IC50)c-KitV654A c-KitD816V127 nM (IC50) 950 nM (IC50)體外研究 Amuvatinib (MP470), a novel receptor tyrosine kinase (RTK) inhibito

4、r has shown growth inhibitory activityagainst a variety of cancer cell lines. Amuvatinib (0.1-10 M, 4 days incubation) is effective on LNCaP andPC-3 cells with IC50s of 4 M and 8 M, respectively. When Erlotinib (10 M) is combined with varyingdoses of Amuvatinib, the IC50 of Amuvatinib decreases to 2

5、 M on LNCaP cells 2.Akt activity (as measured by phosphorylation on Ser473) is significantly reduced by 10 M Amuvatinib(treated for 30 hours) alone but is not reduced by Erlotinib or Imatinib Mesylate (IM). Moreover, Amuvatinibplus Erlotinib completely abolished Akt phosphorylation in LNCaP cells wi

6、th an unchanged total protein levelof Akt 2.Cell Viability Assay 2Cell Line: Prostate cancer cell lines (LNCaP, PC-3 and DU-145)Concentration: 0.1-10 MIncubation Time: 4 daysResult: The IC50 for LNCaP and PC-3 was 4 M and 8 M, respectively. Had only a modesteffect on the viability of DU-145 cells.We

7、stern Blot Analysis 2Cell Line: LNCaP cellsConcentration: 2,5,10 MIncubation Time: 30 hoursResult: Akt activity (as measured by phosphorylation on Ser473) was significantly reduced at 10M.體內(nèi)研究Four LNCaP xenograft arms each with 12 mice are dosed intraperitoneally with DMSO (control) or Erlotinib80 m

8、g/kg or Amuvatinib (MP470) 50 mg/kg or Erlotinib 80 mg/kg plus Amuvatinib 50 mg/kg daily for 2 weeksand then observed for a further 11 days. Individual therapy with Amuvatinib or Erlotinib shows modest tumorgrowth inhibition (TGI), while Amuvatinib plus Erlotinib has a marked effect on TGI (45-65%).

9、 However, due2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEto the high doses of Amuvatinib used, only five or one mouse remained alive in the combination arm at theend of treatment or at the end of the study, respectively. Therefore the Amuvatinib dose is reduced to 10mg/kg or 20 mg/kg for the co

10、mbination treatment. TGI in the group receiving 10 mg/kg Amuvatinib+80 mg/kgErlotinib is not significantly different from the control group. However, mice receiving 20 mg/kgAmuvatinib+80 mg/kg Erlotinib have a significant TGI compared to the control group (p=0.01) 2.Animal Model: Forty eight 6-7 wee

11、k-old SCID male mice with LNCaP xenograft model 2Dosage: 10 mg/kg and 20 mg/kg, 50 mg/kgAdministration: Administered i.p. daily from days 1 to 24Result: Individual therapy showed modest tumor growth inhibition (TGI), while combination had amarked effect on TGI (45-65%).戶使本產(chǎn)品發(fā)表的科研獻 Sci Transl Med. 20

12、18 Jul 18;10(450). pii: eaaq1093. Sci Signal. 2019 Jul 16;12(590). pii: eaav7259. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. David J. Bearss, et al. Pharmaceutical formulations comprising salts of a protein kinase inhibitor and methods of using same.US20080226747A1.2. Qi W, et al. MP470, a novel receptor tyrosine kinase inhibitor, in combination with Erlotinib inhibits the HER family/PI3K/Akt pathway andtumor growth in prostate cancer. BMC Cancer. 2009 May 11;9:142.McePdfHeig