| 包装 | 价格(元) |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
Binding affinity assays | TR-FRET-binding affinity assays were performed for BCL-2, BCL-XL and MCL-1 in 4.52 mM monobasic potassium phosphate, 15.48 mM dibasic potassium phosphate, 1 mM sodium EDTA, 0.05% Pluronic F-68 detergent, 50 mM sodium chloride and 1 mM DTT (pH 7.5). For MCL-1 assays, GST-tagged MCL-1 (1 nM) was mixed with 100 nM f-Bak, 1 nM Tb-labeled anti-GST antibody and compound at room temperature for 60 mins. Fluorescence was measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-GST antibody) emission filters. |
Cell lines | H929 cells |
Preparation method | This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 ℃ for several months. |
Reacting condition | 0 ~ 30 μM; 4 hrs |
Applications | In H929 cells, A-1210477 bound selectively and strongly to MCL-1, and reduced the amount of BIM co-immunoprecipitated with MCL-1 in a dose-dependent manner with an IC50 value in the low-μM range. |
| 产品描述 | A-1210477 is an effective and specific MCL-1 inhibitor with an EC50 value below 5 μmol/L [1]. Selectively, it binds to MCL-1 with an affinity of 0.45 nM [2]. MCL-1, an anti-apoptotic Bcl-2 family member, is an anti-apoptotic protein. It is a key regulator of cancer cell survival [3, 4]. In MCL-1-dependent SVEC cells, treatment with A-1210477 at varying doses, induced cell death in a dose-dependent manner. SYTOX Green exclusion and live-cell imaging were used to determine cell viability. In line with increased potency, cell death was more rapidly induced by A-1210477. To examine the selectivity of A-1210477 for targeting Bcl-2 family members, BcL-xL-, BcL-2-, and MCL-1-dependent SVEC cells were treated with A-1210477. A-1210477 only killed MCL-1-dependent cells. Compared with UMI-77, A-1210477 showed greater potency and specificity as an MCL-1 inhibitor, the EC50 value of UMI-77 is 10 μmol/L [1]. In living cells, A-1210477 disrupted BIM/MCL-1 complexes. In MCL-1-dependent cancer cells, A-1210477 induced the hallmarks of mitochondrial apoptosis. In various malignant cell lines, A-1210477 induced apoptosis, synergizing with navitoclax. Data also demonstrate that A-1210477 acted through an on-target mechanism. It appeared as the first BH3 mimetic targeting MCL-1 [2]. The pharmacokinetics of A-1210477 are not favorable for in vivo use [5]. References: |
m.cnreagent.com