Tideglusib
(Synonyms: 4-苄基-2-(萘-1-基)-[1,2,4]噻二唑烷-3,5-二酮,NP031112) 目录号 : GC14465
A neuroactive thiadiazolidinone
Cas No.:865854-05-3
Sample solution is provided at 25 µL, 10mM.
IC50: A potent, selective and irreversible non-ATP-competitive GSK-3β suppressor with an IC50 of 60 nM.
Tideglusib is a GSK-3 inhibitor currently undergoing phase II clinical trials for Alzheimer disease and progressive supranuclear palsy. Sustained oral administration of Tideglusib to animal models could down-regulates Tau hyper-phosphorylation, reduces brain amyloid plaque load, promotes learning and memory as well as prevents neuronal loss. [1]
In vitro: In vitro studies showed that after the unbound Tideglusib was removed from the reaction medium, the enzyme function could not be recovered. In addition, the dissociation rate constant of the reaction was as low as nearly zero. All above findings suggested that Tideglusib blocked GSK-3 irreversibly. Such irreversibility might be responsible for the non-competitive inhibition pattern with respect to ATP of Tideglusib and perhaps other structurally related compounds. [1]
In vivo: Based on double transgenic mice model co-expressing human mutant APP and tau, a study demonstrated that Tideglusib could suppress GSK-3, reduced amyloid and tau pathologies, blocked neuronal cell death and memory deficits in vivo. [2]
Clinical trial: A pilot, double-blind, placebo-controlled and randomized clinical trial was conducted to study the effect of Tideglusib in AD patients with an escalating dose. Thirty patients with mild to moderate AD were orally administered with Tideglusib in escalating doses of 400, 600, 800 and 1000 mg for periods of 4, 4, 6 and 6 weeks, respectively. This pilot study proved the safety and effectiveness of Tideglusib in AD patients. [3]
References:
[1]Domínguez JM, Fuertes A, Orozco L, Monte-Millan MD, Delgado E and Medina M. Evidence for irreversible inhibition of glycogen synthase kinase-3 by Tideglusib. J Biol Chem. 2012 Jan; 287(2): 893-904.
[2]Serenóa L, Coma M, Rodríguez M, Sánchez-Ferrer P, Sánchez MB, Gich I, Agulló JM, Pérez M, Avila J, Guardia-Laguarta C, Clarimón J, Lleó A, Gómez-Isla T. A novel GSK-3β inhibitor reduces Alzheimer's pathology and rescues neuronal loss in vivo. Neurobiol Dis. 2009 Sep; 35(3): 359-67.
[3]del Ser, T. Phase IIA clinical trial on Alzheimer’s Disease with NP-12, a GSK-3 inhibitor. Alzheimers and Dement. 2010; 6: S147.
| Cell experiment [1]: | |
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Cell lines |
Spodoptera frugiperda Sf21 cells(expressing N-terminal His6-tagged human recombinant GSK-3β) |
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Preparation method |
The solubility of this compound in DMSO >15 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
55μM for 1h at 25 °C . |
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Applications |
Tideglusib blocked GSK-3β irreversibly in Sf21 cells transfected with human recombinant GSK-3β. It could prevent inflammation and neurodegeneration under excitotoxic conditions. |
| Animal experiment [2]: | |
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Animal models |
Transgenic APPsw-tauvlw C57Bl6j/SJL/CBA mixed hybrid genetic mice( overexpressing human mutant APP and a triple human tau mutation (G272V, P301L and R406W at chromosome 17)) |
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Dosage form |
Reconstituted in 26% peg400 (Polyethylene Glycol 400), 15% Chremophor EL and water; 200 mg/kg daily for consecutive months; oral gavage |
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Application |
Treatment with tideglusib resulted in lower levels of tau phosphorylation, decreased amyloid deposition and plaque-associated astrocytic proliferation, protection of neurons in the entorhinal cortex and CA1 hippocampal subfield against cell death, and prevention of memory deficits in this transgenic mouse model |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Domínguez JM, Fuertes A, et al, Evidence for irreversible inhibition of glycogen synthase kinase-3 by Tideglusib. J Biol Chem. 2012 Jan; 287(2): 893-904. [2] Luna-Medina R1, Cortes-Canteli M, et al, NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxic conditions: potential therapeutic role in brain disorders. J Neurosci. 2007 May 23;27(21):5766-76. [3] Serenóa L, Coma M, et al, A novel GSK-3β inhibitor reduces Alzheimer's pathology and rescues neuronal loss in vivo. Neurobiol Dis. 2009 Sep; 35(3): 359-67. | |
| Cas No. | 865854-05-3 | SDF | |
| 别名 | 4-苄基-2-(萘-1-基)-[1,2,4]噻二唑烷-3,5-二酮,NP031112 | ||
| 化学名 | 4-benzyl-2-naphthalen-1-yl-1,2,4-thiadiazolidine-3,5-dione | ||
| Canonical SMILES | C1=CC=C(C=C1)CN2C(=O)N(SC2=O)C3=CC=CC4=CC=CC=C43 | ||
| 分子式 | C19H14N2O2S | 分子量 | 334.39 |
| 溶解度 | ≥ 16.7 mg/mL in DMSO with gentle warming | 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 | 2.9905 mL | 14.9526 mL | 29.9052 mL |
| 5 mM | 0.5981 mL | 2.9905 mL | 5.981 mL |
| 10 mM | 0.2991 mL | 1.4953 mL | 2.9905 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet