| 名稱 | ABT-737 |
| 描述 | ABT-737 is a BH3 mimetic and an inhibitor of Bcl-2, Bcl-xL, and Bcl-w (EC50=30.3 nM/78.7 nM/197.8 nM). ABT-737 exhibits antitumor activity and anti-aging activity. |
| 細(xì)胞實(shí)驗(yàn) | 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]. |
| 激酶實(shí)驗(yàn) | 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]. |
| 動(dòng)物實(shí)驗(yàn) | 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]. |
| 體外活性 | 方法：AML 細(xì)胞系 HL-60 用 ABT-737 (10-250 nM) 處理 24-72 h，通過活細(xì)胞計(jì)數(shù)檢測(cè)細(xì)胞生長(zhǎng)。
結(jié)果：HL-60 細(xì)胞對(duì) ABT-737 顯示出高敏感性，IC50=50 nM。[1]
方法：甲狀腺癌細(xì)胞用 ABT-737 (1 μM) 處理 24 h，通過 flow cytometer 檢測(cè)細(xì)胞周期。
結(jié)果：在所分析的所有五個(gè)細(xì)胞系中，subG1 級(jí)細(xì)胞顯著增加，表明 ABT-737 誘導(dǎo)了細(xì)胞死亡和 DNA 斷裂。ABT-737 處理的乳頭狀 BHT101 和間變性 SW1736 細(xì)胞中處于 subG1 峰的細(xì)胞百分比最高 (54.8% 和 39.9%)。[2] |
| 體內(nèi)活性 | 方法：為檢測(cè)體內(nèi)抗腫瘤活性，將 ABT-737 (20-30 mg/kg，30% propylene glycol+5% Tween 80+65% D5W (5% dextrose in water)，pH 4?5) 腹腔注射給注射 luc-FD/ΔRaf-1:ER 細(xì)胞的 SCID 小鼠，每天一次，持續(xù) 21 天。
結(jié)果：ABT-737 在 20 和 30 mg/kg 劑量水平下分別將白血病負(fù)擔(dān)抑制了 48% 和 53%，并顯著延長(zhǎng)了這種侵襲性白血病模型中小鼠的存活期，中位存活期為 28-32.5 天，而對(duì)照組為 19.5 天。[1] |
| 存儲(chǔ)條件 | keep away from direct sunlight,store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 50 mg/mL (61.47 mM)
|
| 關(guān)鍵字 | Mitophagy | inhibit | mimetic | HCT116 | Apoptosis | BIM | ABT 737 | BH3 | Autophagy | AML | HL-60 | Bcl-2 Family | Mitochondrial Autophagy | BCL-2/BAX | ABT737 | Inhibitor | ABT-737 |
| 相關(guān)產(chǎn)品 | Guanidine hydrochloride | Naringin | Valproic Acid | Taurine | Gefitinib | Aceglutamide | Hydroxychloroquine | Curcumin | Stavudine | Salicylic acid | Paeonol | Sodium 4-phenylbutyrate |
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