| CAS |
No.1222780-33-7 |
| 英文名称 |
TPPU |
| 分子式 |
C16H20F3N3O3 |
| 分子量 |
359.34 |
| 溶解性 |
Soluble in DMSO ≥8mg/mL(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
White to off-white Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| EC |
EINECS 802-607-3 |
| SMILES |
CCC(=O)N1CCC(CC1)NC(=O)NC2=CC=C(C=C2)OC(F)(F)F |
| InChIKey |
AAJMQTLFRTZCJK-UHFFFAOYSA-N |
| InChI |
InChI=1S/C16H20F3N3O3/c1-2-14(23)22-9-7-12(8-10-22)21-15(24)20-11-3-5-13(6-4-11)25-16(17，18)19/h3-6，12H，2，7-10H2，1H3，(H2，20，21，24) |
| PubChem CID |
44142782 |
| 靶点 |
Epoxide Hydrolase |
| 通路 |
Metabolic Enzyme&Protease |
| 背景说明 |
TTPU是一种可溶性环氧化物水解酶(soluble epoxide hydrolase， sEH)抑制剂。 |
| 生物活性 |
TPPU is a soluble epoxide hydrolase (sEH) inhibitor with IC50 values of 37 and 3.7 nM for monkey and human sEH， respectively.[1-3] |
| IC50 |
IC50: 37 nM (Monkey sEH)， 3.7 nM (Human sEH)[1] |
| In Vitro |
可溶性环氧化物水解酶抑制剂 (sEHI) 具有抗炎、抗动脉粥样硬化、抗高血压和镇痛作用[1]。在 Caco-2 细胞通透性测定中，TPPU 快速通过细胞单层，表明其具有良好的肠道通透性[2]。 |
| In Vivo |
TPPU 适用于研究可溶性环氧化物水解酶生物学和含环氧化物脂质在调节炎症性疾病中的作用。TPPU 以 0.3 mg/kg 的剂量口服给药时显示出高血浆浓度和药物样特性。对于 TPPU，Cmax 随着剂量从 0.3 增加到 3 mg/kg[1]。在大鼠饮用水中给药后 (0.2、1 和 5 mg TPPU /L，含 0.2% PEG400)，TPPU 的血液浓度在处理期间呈剂量依赖性增加，8 天后达到几乎稳定的状态[2]。sEH 抑制剂 TPPU 在抑郁症动物模型中显示出抗抑郁作用。在慢性应激小鼠和抑郁症患者的大脑中，sEH 蛋白的表达增加。预防性 sEH 抑制或 sEH-KO 导致对反复社交失败压力的恢复，与 KO 小鼠前额叶皮层和海马体中 BDNF-TrkB 信号增加有关[3]。 |
| 细胞实验 |
Cell monolayers that exceeds a resistance of 300 Ω cm-2 are incubated with either 1 μM or 10 μM of TPPU solution in DMSO on the apical side. Medium samples on the apical and basolateral side are collected and frozen immediately after 1， 3 and 6 hours. The apparent permeability coefficient is calculated for t=1 h[2]. |
| 动物实验 |
Rats: Water is provided ad libitum containing 0.2% PEG400 with and without TPPU at a concentration of 0.2 mg/L， 1 mg/L and 5 mg/L during the treatment period (8 days). Before (0 h) and after 2 h， 4 h， 8 h， 1 d， 2 d， 4 d and 8 d， 10 μL blood are sampled from the tail vain. The blood is directly mixed with 50 μL deionzed water28 and frozen until analysis. On day 8， the animals are sacrificed by cardiac puncture after anesthesia. Plasma and whole blood are sampled[2]. Monkeys: TPPU is prepared in 0.3， 1 and 3 mg/kg doses and is administered to four animals with 48 h dosing intervals based on the t1/2 of the compound obtained from the first cassette dosing. Blood is collected from animals at time points 0， 0.25， 0.5， 1， 2， 3， 4， 8， 24 and 48 h after each dosing for analysis[1]. |
| 数据来源文献 |
[1]. Ulu A， et al. Pharmacokinetics and in vivo potency of soluble epoxide hydrolase inhibitors in cynomolgus monkeys. Br J Pharmacol. 2012 Mar;165(5):1401-12.
[2]. Ostermann AI， et al. Oral treatment of rodents with soluble epoxide hydrolase inhibitor 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU): Resulting drug levels and modulation of oxylipin pattern. Prostaglandins Other Lipid Mediat. 2015 Sep;121(Pt A):131-7.
[3]. Ren Q， et al. Gene deficiency and pharmacological inhibition of soluble epoxide hydrolase confers resilience to repeated social defeat stress. Proceedings of the National Academy of Sciences of the United States of America (2016)， 113(13)， E1944-E1952. |
| 规格 |
1mg 5mg 10mg 25mg 50mg 100mg |
| 单位 |
瓶 |
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