Amuvatinib-hydrochloride-MP470-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAmuvatinib hydrochlorideCat. No.: HY-10206ACAS No.: 1055986-67-8Synonyms: MP470 hydrochloride; HPK 56 hydrochloride分式: CHNOS.xHCl作靶点: c-Kit; PDGFR作通路: Protein Tyrosine Kinase/RTK储存式: Please store the product under the recommende

2、d conditions inthe COA.BIOLOGICAL ACTIVITY物活性 Amuvatinib hydrochloride (MP470 hydrochloride)种多靶点受体酪氨酸激酶抑制剂，抑制 c-Kit(D816V)，c-Kit (D816H)，c-Kit (V560G)，c-Kit (V654A)，PDGFR (D842V)，PDGFR (V561D)，IC50 分别为 950 nM，10 nM，34 nM，127 nM，81 nM 和 40 nM 1。具有抗肿瘤活性 2。IC50 & Target PDGFRV561D PDGFRD842V c-KitD816H

3、 c-KitV560G40 nM (IC50) 81 nM (IC50) 10 nM (IC50) 34 nM (IC50)c-KitV654A c-KitD816V127 nM (IC50) 950 nM (IC50)体外研究Amuvatinib (MP470), a novel receptor tyrosine kinase (RTK) inhibitor has shown growth inhibitory activityagainst a variety of cancer cell lines. Amuvatinib (0.1-10 M, 4 days incubation)

4、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 M on LNCaP cells 2.Akt activity (as measured by phosphorylation on Ser473) is significantly reduced by 10 M Amuvatinib

5、(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 with an unchanged total protein levelof Akt 2.Cell Viability Assay 2Cell Line: Prostate cancer cell lines (LNCaP, PC-3 an

6、d DU-145)Concentration: 0.1-10 M1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEIncubation 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.Western Blot Analysis 2Cell Line: LNCaP cellsConcentration: 2,5,10 MIncu

7、bation Time: 30 hoursResult: Akt activity (as measured by phosphorylation on Ser473) was significantly reduced at 10M.体内研究 Four LNCaP xenograft arms each with 12 mice are dosed intraperitoneally with DMSO (control) or Erlotinib80 mg/kg or Amuvatinib (MP470) 50 mg/kg or Erlotinib 80 mg/kg plus Amuvat

8、inib 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%). However, dueto the high doses of Amuvatinib used, only five or one m

9、ouse 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 combination treatment. TGI in the group receiving 10 mg/kg Amuvatinib+80 mg/kgErlotinib is not significantly different f

10、rom 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 week-old SCID male mice with LNCaP xenograft model 2Dosage: 10 mg/kg and 20 mg/kg, 50 mg/kgAdministration: Administered i

11、.p. daily from days 1 to 24Result: Individual therapy showed modest tumor growth inhibition (TGI), while combination had amarked effect on TGI (45-65%).户使本产品发表的科研献 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Sci Signal. 2019 Jul 16;12(590). pii: eaav7259. Harvard Medical School LINCS LIBRARY

12、See more customer validations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE1. 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.McePdfHeightCa