ABT-737
作者：齐岳
发布时间：2023-09-13
16:35:37
点击数：
产品名称：ABT-737
产品描述：
| 产品描述 | ABT-737 is a BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w (EC50s: 78.7/30.3/197.8 nM). |
| 靶点活性 | Bcl-2:30.3 nM(EC50, cell free), Bcl-xL:78.7 nM(EC50, cell free), Bcl-W:197.8 nM(EC50, cell free), Bcl-B:1820 nM(EC50, cell free) |
| 体外活性 | ABT-737 induced the disruption of the BCL-2/BAX complex and BAK-dependent but BIM-independent activation of the intrinsic apoptotic pathway. In cells with phosphorylated BCL-2 or increased MCL-1, ABT-737 was inactive. Inhibition of BCL-2 phosphorylation and reduction of MCL-1 expression restored sensitivity to ABT-737 [1]. ABT-737 inhibited proliferation and induced apoptosis in SGC-7901 and MGC-803 cells in concentration- and time-dependent manners. ABT-737 disturbed the binding of B cell lymphoma (Bcl)-2 homologous antagonist killer and Bcl-extra large [2]. ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation. ABT-737 exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells [3]. |
| 体内活性 | ABT-737 and ATO significantly suppressed SGC-7901 xenograft growth, synergistically inhibited tumour growth and induced apoptosis in vivo [2]. H146 tumours were treated with a single dose of ABT-737. A significant increase in caspase-3-positive cells was noted as early as 2 h after treatment, with a 12-fold increase achieved within 16 h. Examination of liver, heart, and intestine revealed no increase in caspase-3 activation in these normal tissues [3]. Treatment with either ABT-737 (100 mg/kg/day) was initiated on the day following inoculation. On day 21 post-treatment, the mean tumor volume, weight, and serum level of sIL-2Ra were significantly lower than those of vehicle-treated mice [4]. |
| 激酶实验 | To determine the binding affinity of GST-BCL-2 family proteins to the FITCconjugated BH3 domain of BIM, FPAs were performed as described. Briefly, 100 nM of GST-BCL-2 family fusion proteins were incubated with serial dilutions of ABT-737 in PBS for 2 min. Then, 20 nM of FITC-BIM BH3 peptide was added. Fluorescence polarization was measured using a Detection System after 10 min using the 96-well black plate. IC50s were determined [1]. |
| 细胞实验 | Cells were seeded into 96-well plates (5 × 10^3 cells/well) and cultured for 12 h at 37 °C, as described above. Then, the medium was replaced with RPMI 1640 containing various concentrations of ATO (1, 2, 4 and 8 nM), ABT-737 (2.5, 5, 10 and 20 μM) or combinations of ATO and ABT-737, and cells were cultured for a further for 24, 48 or 72 h at 37 °C. Cells cultured in RPMI 1640 containing an equal volume of 0.01 M phosphate-buffered saline (PBS, pH 7.4; vehicle) served as controls. Cell viability was measured using Cell Counting Kit-8, according to the manufacturer's instructions. The cell proliferation rate was calculated according to the formula: experimental optical density (OD) value/control OD value × 100%. Experiments were repeated in triplicate [2]. |
| 动物实验 | Mice were housed under standard conditions and had free access to water and food, under a 12-h light/12-h dark cycle in a room maintained at 18 – 22 °C and 50 – 65% humidity. SGC7901 cells (5 × 10^6) were subcutaneously inoculated into the right flank of BALB/c mice (H-2b). Tumour volume was measured using callipers and estimated according to the formula: π ? 6 × a2 × b, where a was the short axis, and b was the long axis. After 10 days, when the tumours had reached about 0.2 cm in diameter, the mice were randomly assigned to four groups (n = 8 per group), using a randomization schedule generated by the SAS software package. The groups were: control; ABT-737; ATO; ABT737 + ATO. They received, respectively: vehicle (1% DMSO, 99% 0.01 M PBS; pH 7.4); ABT-737 (50 mg/kg); ATO (2.5 mg/kg); ABT737 (50 mg/kg) + ATO (2.5 mg/kg) intraperitoneally (i.p.) every 2 days. Drugs were dissolved in the vehicle solution. To standardize the experiments, each mouse received a similar volume of solution. After 15 days, the mice were euthanized and the solid SGC-7901 tumours were harvested, fixed with 4% paraformaldehyde, frozen in optimal cutting temperature compound and stored at –80 °C [2]. |
| 分子量 | 813.43 |
| 分子式 | C42H45ClN6O5S2 |
| CAS No. | 852808-04-9 |
存储
| Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
H2O: <1 mg/mL
Ethanol: <1 mg/mL
DMSO: 93 mg/mL (114.3 mM)
( < 1 mg/mL refers to the product slightly soluble or insoluble )
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