Product Introduction
Bioactivity


英文名: Mubritinib

描述: Mubritinib (TAK-165) 是选择性的EGFR2/HER2抑制剂，IC50值为6 nM。

细胞实验: Cells are seeded into 6-well plates and cultured overnight. Mubritinib is then added at various concentrations, and the cells are treated continuously for 72 hours. After the incubation period, cells are counted for the measurement of antiproliferative activity.(Only for Reference)

激酶实验: Inhibition of HER2/erbB2 tyrosine kinase activity: BT-474 cells are seeded on 24-well plates and cultured overnight. Mubritinib is then added at various concentrations. After incubation for 2 hours, the cells are harvested directly into sodium dodecyl sulfate (SDS)-sample buffer (200 μL). Aliquots containing equal amounts of total cell extract are run on 7.5% to 15% gradient SDS–polyacrylamide gel electrophoresis (PAGE). Following electrophoresis, proteins are transferred onto a polyvinylidene fluoride (PVDF) membrane, for western blot analysis using a relevant primary antibody. Detection of protein is accomplished by an enhanced chemiluminescent (ECL) detection method. The extent of tyrosine phosphorylation of HER2/erbB2 is measured by the LAS-1000 plus lumino-image analyser. The concentration of Mubritinib that inhibits HER2/erbB2 phosphorylation by 50% (IC50) is calculated from a dose–response curve generated by least-squares linear regression of the response using SAS software.

体外活性: Mubritinib displays > 4000-fold selectivity over other tyrosine kinases, such as EGFR, FGFR, PDGFR, Jak1, Src and Blk. Mubritinib even at low concentration of 0.1 μM significantly blocks HER2 phosphorylation, leading to the downregulation of PI3K-Akt and MAPK pathway in cell line BT474 with high level of HER2. Mubritinib not only exhibits highly potent antiproliferative effect in ErbB2-overexpressing cancer cell line BT474 with an IC50 of 5 nM, but also displays marked antiproliferative effects in cell lines with HER2 expressed weakly with IC50 of 53 nM, 90 nM and 91 nM for LNCaP, LN-REC4 and T24, respectively. Mubritinib displays no inhibitory activities against PC-3 cells with HER2 expressed very faintly with IC50 of 4.62 μM, as well as EGFR-overexpressing HT1376 and ACHN cell lines with IC50 of >25 μM. [1]

体内活性: Mubritinib significantly inhibits LN-REC4 xenograft with treatment/control tumor volume ratio of 26.5%. Although ineffective to inhibit the growth of UMUC-3 and ACHN cells in vitro (IC50s of 1.812 and >25 μM, respectively), oral administration of Mubritinib (10 or 20 mg/kg per day) significantly inhibits the growth of UMUC-3 and ACHN xenografts with treatment/control tumor volume ratio of 22.9% and 26%, respectively, as compared with Herceptin (20 mg/kg) which is ineffective to UMUC-3 tumor growth. [1]

存储条件: store at low temperaturePowder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 35.1 mg/mL (75 mM)


关键字: EGFR | Epidermal growth factor receptor | inhibit | Inhibitor | HER1 | ErbB-1 | Mubritinib | TAK165 | TAK 165

相关产品: Avitinib maleate | Tyrosine kinase-IN-7 | Canertinib dihydrochloride | Cloperastine fendizoate | EGFR-IN-87 | Naluzotan | SYR127063 | Tyrphostin B44, (+) enantiomer | EGFR-IN-89 | MTX-241F

相关库: Drug Repurposing Compound Library | Anti-Prostate Cancer Compound Library | Anti-Cancer Drug Library | Membrane Protein-targeted Compound Library | Kinase Inhibitor Library | Inhibitor Library | Anti-Cancer Clinical Compound Library | Tyrosine Kinase Inhibitor Library | Highly Selective Inhibitor Library | Anti-Cancer Active Compound Library