DAPT

製品コードS2215 バッチS221508

印刷

化学情報

Chemical Structure Synonyms GSI-IX, LY-374973 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C23H26F2N2O4
分子量 432.46 CAS No. 208255-80-5
Solubility (25°C)* 体外 DMSO 86 mg/mL (198.86 mM)
Ethanol 39 mg/mL (90.18 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 DAPT (GSI-IX、LY-374973) は新規の γ-セクレターゼ 阻害剤であり、HEK 293 細胞で 20 nM の IC50 で Aβ 産生を阻害します。 DAPT はヒト舌癌細胞のアポトーシス(apoptosis) を促進し、オートファジー (autophagy) を調節します。
in vitro In human primary neuronal cultures, DAPT also shows inhibitory effects on Aβ production with IC50 of 115 nM and 200 nM respectively for Aβ total and Aβ42, which is 5-10-fold lower than is observed in HEK 293 cells. [1] A recent study shows that this compound inhibits the proliferation of SK-MES-1 cells in a concentration-dependent manner with IC50 of 11.3 μM. In addition, it also induces caspase-dependent and caspase-independent apoptosis in lung squamous cell carcinoma cells by inhibiting Notch receptor signaling pathway. [2]
in vivo DAPT administration (100mg/kg) leads to a robust and sustained pharmacodynamic effect in PDAPP mice that this compound levels in the brain exceeds 100 ng/g within 1 hour and persists up to 18 hours after administration, with peak levels of 490 ng/g observed after 3 hour. And during the period, this chemical (100 mg/kg) also reduces the cortical total Aβ and Aβ42 in a dose-dependent manner with a 50% reduction. [1] In rat cerebral cortexes, this compound (40 mg/kg) suppresses the LPS-induced activity of γ-secretase and increases the cell apoptosis with the prolonged neuroinflammation. [3]

プロトコル(参考用のみ)

キナーゼアッセイ In vitro Aβ reduction assays
Human embryonic kidney cells (American Type Culture Collection CRL-1573), transfected with the gene for APP751 (HEK 293) are used for routine Aβ reduction assays. Cells are 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. DAPT are diluted from stock solutions in dimethylsulfoxide (DMSO) to yield a final concentration equal to 0.1% DMSO in media. Cells are pre-treated for 2 hours at 37 °C with this compound, media are aspirated off and fresh compound solutions applied. After an additional 2-hour treatment period, conditioned media is drawn off and analyzed by a sandwich ELISA (266–3D6) specific for total Aβ. Reduction of Aβ production is measured relative to control cells treated with 0.1% DMSO and expressed as a percentage inhibition. Data from at least six doses in duplicate are fitted to a four-parameter logistical model using XLfit software in order to determine potency. Human and PDAPP mouse neuronal cultures are grown in serum-free media to enhance their neuronal characteristics, and appeared to be greater than 90% neurons after maturation prior to use. Conditioned media to establish baseline Aβ values are collected by adding fresh media to each well and incubated for 24 hours at 37 °C in the absence of this chemical. Cultures are then treated with fresh media containing this compound at the desired range of concentrations for an additional 24 hours at 37 °C, and conditioned media collected. For the measurement of total Aβ, samples are analyzed with the same ELISA (266–3D6) as used for the HEK 293 cell assays. Analyses of samples for Aβ42 production are performed by a separate ELISA (21F12–3D6) that utilizes a capture antibody specific for the Aβ42 C-terminus. Inhibition of production for both total Aβ and Aβ42 are determined by the difference between the values for the compound treatment and baseline periods. After plotting percentage inhibition versus this compound concentration, data are analyzed with XLfit software, as above, to determine potency.
細胞アッセイ 細胞株 SK-MES-1
濃度 2.5 μM to 160 μM
反応時間 72 hours
実験の流れ Cells are seeded into 96-well plates and exposed to 0.1% DMSO or DAPT at concentrations in the range of 2.5 μM–160 μM for 72 hours. Cytotoxicity is determined with 3-(4, 5)-dimethylthiahiazo-(-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) dye reduction assay with minor modifications. Briefly, after incubation with this compound, 20 μL MTT solution (5 mg/mL in PBS) is added to 180 μL medium in each well and plates are incubated for 4 hours at 37 °C, and subsequently 150 μL DMSO is added to each well, and mixed by shaking at room temperature for 15 minutes. Absorption is measured by an enzyme-linked immunosorbent assay at 490 nm to determine absorbance values. α-MEM supplemented with the same amount of MTT solution and solvent is used as blank solution. The IC50 value is calculated using PROBIT program in SPSS.
動物実験 動物モデル Heterozygous PDAPP transgenic mice overexpressing the APPV717F mutant form of the amyloid precursor protein.
投薬量 ≤100 mg/kg
投与方法 Administered via p.o.

参考

  • https://pubmed.ncbi.nlm.nih.gov/11145990/
  • https://pubmed.ncbi.nlm.nih.gov/22583356/
  • https://pubmed.ncbi.nlm.nih.gov/22445932/

カスタマーフィードバック

Data from [Data independently produced by Oncogene, 2014, 10.1038/onc.2014.319]

Data from [Data independently produced by Stem Cells, 2014, 32(1), 301-12]

Data from [Data independently produced by Dis Model Mech, 2013, 6(6), 1494-506]

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長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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