Edonerpic maleate (T-817 maleate)
(Synonyms: 1-(3-(2-(苯并[B]噻吩-5-基)乙氧基)丙基)氮杂环丁烷-3-醇马来酸,T-817 maleate; T-817MA) 目录号 : GC30823
T-817MA is a newly synthesized agent for Alzheimer's disease (AD) treatment
Cas No.:519187-97-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Neuron/Glia Coculture |
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Preparation Method |
T-817MA( Edonerpic maleate (T-817 maleate)) was added to the cocultures at concentrations of 0 (control), 0.01, 0.1, and 1 M, and the cells were subsequently incubated for 5 min or 24 h. H2O2 was then added to the coculture at a concentration of 100 M, and the cells were incubated for another 24 h. For the normal group, the preparations were maintained in the medium with neither T-siM nor H2O2. Neuronal cell viability was quantified by measuring the MAP2 immunoreactivity |
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Reaction Conditions |
0, 0.01, 0.1, and 1 µM;5min or 24h |
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Applications |
The 100 µM H2O2 treatment greatly reduced the number of surviving neurons in the culture. When T-817MA was pretreated for 24 h, T-817MA significantly prevented this neuronal damage at 0.1 and 1 µM. Conversely, a brief (5 min) pretreatment with T-817MA, followed by its continuous presence with H2O2, did not rescue the H2O2-treated neurons from death. |
| Animal experiment [2]: | |
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Animal models |
Wistar rats (7 weeks) |
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Preparation Method |
Rats were divided into five groups: vehicle (n= 11), Aβ infusion control (n= 10), Aβ infusion + high-dose T-817MA (8.4 mg/kg) (n= 11), Aβ infusion + low-dose T-817MA (0.84 mg/kg) (n= 9) and Aβ infusion + donepezil (0.5 mg/kg) (n= 7). |
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Dosage form |
0.84/8.4 mg/kg/day, p.o. |
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Applications |
Rats given Aβ infusions for 10 weeks displayed spatial memory impairments and a decrease in neurogenesis compared with those infused with vehicle. Treatment of the Aβ-infused rats with T-817MA (8.4 mg/kg/day;p.o.) significantly increased hippocampal neurogenesis and ameliorated spatial learning impairments. |
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References: [1]. Hirata K, Yamaguchi H, et,al. A novel neurotrophic agent, T-817MA [1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl}-3-azetidinol maleate], attenuates amyloid-beta-induced neurotoxicity and promotes neurite outgrowth in rat cultured central nervous system neurons. J Pharmacol Exp Ther. 2005 Jul;314(1):252-9. doi: 10.1124/jpet.105.083543. Epub 2005 Mar 29. PMID: 15798005. |
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T-817MA [1-{3-[2-(1-Benzothiophen-5-yl)ethoxy] propyl}-3-azetidinol maleate] is a newly synthesized agent for Alzheimer's disease (AD) treatment with neuroprotective effects against toxicity from amyloid-β peptide (Aβ) and actions promoting neurite outgrowth[1].
T-817MA was pretreated for 24 h,T-817MA significantly prevented neuronal damage caused by H2O2 treatment at 0.1 and 1 uM[1]. T-817MA at 0.1 and 1microM attenuated the neurotoxicity in a dose-dependent way and the protective effect required pretreatment for more than 8h. T-817MA attenuated SNP-induced decrease in mitochondrial transmembrane potential[5].
T-817MA (8.4 mg/kg/day; p.o.) hippocampal neurogenesis was significantly increased and spatial learning disabilities were improved in rats treated with aβ[2]. T-817MA (10 or 20 mg/kg) or vehicle was administered for 14 days. Administration of T-817MA at 20 mg/kg ameliorated Prepulse inhibition (PPI) deficits and completely reversed the decrease in the number of PV-positive GABAergic neurons in rats given MK-801[3]. T-817MA (0.21 or 0.07 mg/ml, p.o.) is effective in ameliorating sensorimotor gating deficits caused by chronic PCP treatment, possibly via neuroprotective actions[4]. T-817MA prevented the progression of motor deficit and the loss of spinal cord motor neurons in P301L mice[6]. Sustained oral administration of T-817MA significantly reduced the extent of auditory threshold shifts and outer hair cell loss, indicating that T-817MA attenuates the intense pressure-induced cochlear damage that accompanies inner ear barotrauma via antioxidative activity[7].
References:
[1]. Hirata K, Yamaguchi H, et,al.A novel neurotrophic agent, T-817MA [1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl}-3-azetidinol maleate], attenuates amyloid-beta-induced neurotoxicity and promotes neurite outgrowth in rat cultured central nervous system neurons. J Pharmacol Exp Ther. 2005 Jul;314(1):252-9. doi: 10.1124/jpet.105.083543. Epub 2005 Mar 29. PMID: 15798005.
[2]. Kimura T, Hong Nguyen PT, et,al.T-817MA, a neurotrophic agent, ameliorates the deficits in adult neurogenesis and spatial memory in rats infused i.c.v. with amyloid-beta peptide. Br J Pharmacol. 2009 Jun;157(3):451-63. doi: 10.1111/j.1476-5381.2009.00141.x. Epub 2009 Apr 3. PMID: 19371351; PMCID: PMC2707991.
[3]. Uehara T, Sumiyoshi T, et,al. T-817MA, a novel neurotrophic agent, ameliorates loss of GABAergic parvalbumin-positive neurons and sensorimotor gating deficits in rats transiently exposed to MK-801 in the neonatal period. J Psychiatr Res. 2012 May;46(5):622-9. doi: 10.1016/j.jpsychires.2012.01.022. Epub 2012 Feb 18. PMID: 22342346.
[4]. Seo T, Sumiyoshi T, et,al. T-817MA, a novel neurotrophic compound, ameliorates phencyclidine-induced disruption of sensorimotor gating. Psychopharmacology (Berl). 2008 Apr;197(3):457-64. doi: 10.1007/s00213-007-1057-8. Epub 2008 Feb 5. PMID: 18251012.
[5]. Fukushima T, Koide M, et,al.T-817MA, a novel neurotrophic agent, improves sodium nitroprusside-induced mitochondrial dysfunction in cortical neurons. Neurochem Int. 2006 Jan;48(2):124-30. doi: 10.1016/j.neuint.2005.08.012. Epub 2005 Oct 10. PMID: 16219389.
[6]. Fukushima T, Nakamura A, et,al.T-817MA, a neuroprotective agent, attenuates the motor and cognitive impairments associated with neuronal degeneration in P301L tau transgenic mice. Biochem Biophys Res Commun. 2011 Apr 22;407(4):730-4. doi: 10.1016/j.bbrc.2011.03.091. Epub 2011 Mar 31. PMID: 21439944.
[7]. Maekawa H, Matsunobu T, et,al.Protective effect of neurotrophic agent T-817MA against inner ear barotrauma in the guinea pig. J Pharmacol Sci. 2011;117(1):67-70. doi: 10.1254/jphs.11033sc. Epub 2011 Aug 25. PMID: 21869565.
T-817MA [1-{3-[2-(1-Benzothiophen-5-yl)ethoxy] propyl}-3-azetidinol maleate] 是一种新合成的阿尔茨海默病 (AD) 治疗剂，具有神经保护作用β-淀粉样肽 (Aβ) 的毒性和促进神经突生长的作用[1].
T-817MA 预处理 24 小时后，T-817MA 在 0.1 和 1 uM[1] 时显着防止 H2O2 处理引起的神经元损伤。 0.1 和 1microM 的 T-817MA 以剂量依赖的方式减弱神经毒性，保护作用需要预处理 8 小时以上。 T-817MA 减弱了 SNP 诱导的线粒体跨膜电位降低[5]。
在用 aβ[2] 处理的大鼠中，T-817MA（8.4 毫克/千克/天；口服）显着增加海马神经发生并改善空间学习障碍。 T-817MA（10 或 20 mg/kg）或载体给药 14 天。在给予 MK-801[3] 的大鼠中，以 20 mg/kg 的剂量施用 T-817MA 可改善前脉冲抑制 (PPI) 缺陷并完全逆转 PV 阳性 GABA 能神经元数量的减少。 T-817MA（0.21 或 0.07 mg/ml，口服）可有效改善由慢性 PCP 治疗引起的感觉运动门控缺陷，可能是通过神经保护作用[4]。 T-817MA 阻止了 P301L 小鼠运动缺陷的进展和脊髓运动神经元的丢失[6]。持续口服 T-817MA 可显着降低听阈偏移和外毛细胞丢失的程度，表明 T-817MA 通过抗氧化活性减轻内耳气压伤伴随的强压诱导的耳蜗损伤[7].
| Cas No. | 519187-97-4 | SDF | |
| 别名 | 1-(3-(2-(苯并[B]噻吩-5-基)乙氧基)丙基)氮杂环丁烷-3-醇马来酸,T-817 maleate; T-817MA | ||
| Canonical SMILES | OC1CN(CCCOCCC2=CC=C3C(C=CS3)=C2)C1.O=C(O)/C=C\C(O)=O | ||
| 分子式 | C20H25NO6S | 分子量 | 407.48 |
| 溶解度 | DMSO : 155 mg/mL (380.39 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4541 mL | 12.2705 mL | 24.5411 mL |
| 5 mM | 0.4908 mL | 2.4541 mL | 4.9082 mL |
| 10 mM | 0.2454 mL | 1.2271 mL | 2.4541 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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T-817MA, a novel neurotrophic compound, ameliorates phencyclidine-induced disruption of sensorimotor gating
2008 Apr;197(3):457-64.PMID: 18251012DOI: 10.1007/s00213-007-1057-8
Rationale: Neurodegenerative changes have been suggested to provide a basis for the pathophysiology of schizophrenia. T-817MA (1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl} azetidin-3-ol maleate) is a novel compound with neuroprotective and neurite-outgrowth effects, as elicited in rat primary cultured neurons. Objectives: We examined the effect of T-817MA on phencyclidine (PCP)-induced disruption of prepulse inhibition (PPI), a measure of sensorimotor gating, in male Wistar rats. Materials and methods: In chronic experiments, male Wistar rats were injected intermittently with PCP (2.0 mg/kg, i.p., three times per week) or vehicle (saline, 2.0 ml/kg) for 1 month. T-817MA (0.21 or 0.07 mg/ml, p.o.) or distilled water was administered throughout the study period. In an acute experiment, T-817MA (8.4 mg/kg, p.o.) or distilled water was administered, followed by treatment with PCP (2.0 mg/kg, i.p.) or vehicle (saline, 2.0 ml/kg), before PPI measurements. Results: Intermittent administration of PCP for 1 month induced persistent disruption of PPI. Coadministration of T-817MA at 0.21 mg/ml but not 0.07 mg/ml completely blocked PCP-induced disruption of PPI, whereas T-817MA (0.21 mg/ml) by itself did not show a significant effect on PPI in control rats. On the other hand, single administration of T-817MA did not affect PPI disruption by acute treatment with PCP. Conclusions: These results suggest that T-817MA is effective in ameliorating sensorimotor gating deficits caused by chronic PCP treatment, possibly via neuroprotective actions. Our findings provide a novel therapeutic approach for patients with schizophrenia.
T-817MA, a novel neurotrophic agent, improves sodium nitroprusside-induced mitochondrial dysfunction in cortical neurons
Neurochem Int.2006 Jan;48(2):124-30.PMID: 16219389DOI: 10.1016/j.neuint.2005.08.012 Abstract
1-{3-[2-(1-Benzothiophen-5-yl)ethoxy]propyl}-3-azetidinol maleate (T-817MA), a novel neurotrophic agent, protects against amyloid-beta peptide- or hydrogen peroxide-induced neuronal death. The exact mechanism of the neuroprotection is not known. This study examines the effects of T-817MA on oxidative stress-induced cytotoxicity in primary rat cortical neurons. Treatment with the NO donor sodium nitoroprusside (SNP) at 300microM decreased cell viability and induced apoptotic cell death. SNP-induced neuronal toxicity was accompanied by a decrease in mitochondrial transmembrane potential without an increase in the expression of CHOP and GRP78 mRNAs, endoplasmic reticulum stress makers. T-817MA at 0.1 and 1microM attenuated the neurotoxicity in a dose-dependent way and the protective effect required pretreatment for more than 8h. T-817MA attenuated SNP-induced decrease in mitochondrial transmembrane potential. In addition, the agent reduced SNP-induced increase in mitochondrial reactive oxygen species (ROS) production. The effects of T-817MA on SNP-induced decrease in cell viability and SNP-induced increase in mitochondrial ROS production were blocked by cycloheximide. These results suggest that T-817MA improves SNP-induced mitochondrial dysfunction in cortical neurons in a newly synthesized protein-mediated mechanism and this effect contributes to its neuroprotective effect.
T-817MA, a novel neurotrophic agent, ameliorates loss of GABAergic parvalbumin-positive neurons and sensorimotor gating deficits in rats transiently exposed to MK-801 in the neonatal period
J Psychiatr Res.2012 May;46(5):622-9.PMID: 22342346DOI: 10.1016/j.jpsychires.2012.01.022
T-817MA [1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate] is a newly synthesized neuroprotective agent for the treatment of psychiatric disorders characterized by cognitive disturbances, such as Alzheimer's disease. Cognitive impairment has also been suggested to be a cardinal feature of schizophrenia. We sought to determine whether T-817MA would ameliorate sensorimotor gating deficits and loss of parvalbumin (PV)-positive γ-aminobutyric acid (GABA) neurons in the brain of rats transiently exposed to MK-801, an N-methyl-d-aspartate receptor blocker, in the neonatal stage, as an animal model of schizophrenia. Prepulse inhibition (PPI) was examined in rats treated neonatally with MK-801 (postnatal day; PD 7-10, 0.2 mg/kg/day, s.c.) or vehicle at PD 35 and PD 63. The number of PV-positive GABAergic neurons in the medial prefrontal cortex (mPFC) and the hippocampus was measured after the behavioral assessments. T-817MA (10 or 20 mg/kg) or vehicle was administered for 14 days (on PD 49-62). Administration of T-817MA at 20 mg/kg, but not 10 mg/kg, ameliorated PPI deficits and completely reversed the decrease in the number of PV-positive GABAergic neurons in rats given MK-801. These results indicate that T-817MA may provide a novel therapeutic approach for the treatment of cognitive deficits of schizophrenia.