化合物DAPT T6202

Product Introduction
Bioactivity


英文名: DAPT

描述: DAPT (LY-374973) 是一种 γ 分泌酶抑制剂，抑制总 Aβ 和 Aβ42 (IC50=115/200 nM)，具有口服活性。DAPT 也是一种 Notch 抑制剂。DAPT 可以诱导细胞分化、诱导细胞自噬和凋亡。

细胞实验: Human embryonic kidney cells, transfected with the gene for APP751 (HEK 293) were used for routine Ab reduction assays. The Ab peptides secreted from these cells have been characterized previously. Cells were plated in 96-well plates and allowed to adhere overnight in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% heat-inactivated fetal bovine serum. For compound screening and dose±response testing, compounds were diluted from stock solutions in DMSO to yield a final concentration equal to 0.1% DMSO in media. Cells were pre-treated for 2 h at 378C with compounds, media were aspirated off and fresh compound solutions applied. After an additional 2-h treatment period, conditioned media were drawn off and analyzed by a sandwich ELISA (266±3D6) specific for total Ab. Reduction of Ab production was measured relative to control cells treated with 0.1% DMSO and expressed as percentage inhibition. Data from at least six doses in duplicate were fitted to a four-parameter logistical model using XLfit software in order to determine potency [1].

动物实验: All studies were conducted with three- to four-month-old heterozygous PDAPP transgenic mice overexpressing the APPV717F a mutant form of the amyloid precursor protein. These animals have been previously shown to exhibit many of the neuropathological features of AD and to produce high levels of Ab in a regionally specific manner. Each treatment group (n=10) consisted of equal numbers of age-matched male and female animals that were fasted overnight prior to treatment. Both treatment and control groups were dosed at a volume of 10 mL/kg with compound formulated in corn oil, 5% (v/v) ethanol or vehicle alone. Tissues were processed and all Ab and APP measurements were made as described previously. After removal of the brain, the cortex from one hemisphere was homogenized, extracted with 5 M guanidine, 50 mM Tris ± pH 8.0, centrifuged, and the supernatant was used for Ab measurements. Cortex from the other hemisphere was snap frozen for analysis of compound levels. Ab levels were expressed as ng/g of wet tissue weight, and percentage reductions were calculated relative to the mean Ab level of tissue from vehicle-treated control animals. Data were analyzed with Mann± Whitney non-parametric statistics to assess significance [1].

体外活性: 方法：卵巢肿瘤干细胞 (OCSC) HO8910 和 SKOV3 用 DAPT (1-20 μg/mL) 处理 24-72 h，使用 MTT 方法检测细胞活力。结果：DAPT 孵育后，观察到细胞自我更新和增殖显著减少。DAPT 诱导对 HO8910 和 SKOV3 OCSC 样细胞的浓度依赖性抗增殖作用。[1]方法：肿瘤细胞 GH3 和原代 GHoma 用 DAPT (20-100 nM) 处理 24 h，使用 Transwell 方法检测细胞迁移情况。结果：DAPT 抑制 GH3 细胞和原代 GHoma 细胞迁移。[2]

体内活性: 方法：为检测体内抗肿瘤活性，将 DAPT (1-5 mg/kg) 腹腔注射给携带大鼠垂体肿瘤 GH3 的 athymic immune-deficient nude 小鼠模型，每天一天，持续十五天。结果：DAPT 治疗显著抑制了肿瘤生长。DAPT 治疗的肿瘤中 Notch2 和 DLL3 的表达下调，DLL4 和 VEGF 表达没有差异。[2]方法：为研究对顺铂肾损伤的作用，将 DAPT (15 mg/kg in 20%Captisol) 腹腔注射给 cisplatin 引起肾损伤的 C57BL/6J 小鼠模型，每天一次，持续五天。结果：DAPT 减轻了顺铂诱导的肾小管损伤和肾小球滤过率的降低。Notch 信号通路可能是缓解顺铂化疗相关肾脏并发症的潜在治疗靶点。[3]

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: H2O : Insoluble
DMSO : 43.2 mg/mL (100 mM)


关键字: Gamma secretase | Amyloid-β | DAPT | Inhibitor | Autophagy | LY374973 | Apoptosis | Abeta | LY 374973 | Notch | γ-secretase | inhibit | β-amyloid peptide

相关产品: Citric acid | Mycophenolic acid | 2,5-dimethyl Celecoxib | STF-118804 | Sulforaphane | Bacopaside II | Nystatin | Xanthurenic Acid | ZINC69391 | Bafilomycin A1

相关库: Anti-Neurodegenerative Disease Compound Library | Wnt/Hedgehog/Notch Compound Library | Anti-Breast Cancer Compound Library | Bioactive Compounds Library Max | Human Metabolite Library | Inhibitor Library | Apoptosis Compound Library | Anti-Pancreatic Cancer Compound Library | Preclinical Compound Library | Stem Cell Differentiation Compound Library

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注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途