TDZD-8
(Synonyms: GSK-3β Inhibitor I; NP 01139) 目录号 : GC14840
A selective inhibitor of GSK3β
Cas No.:327036-89-5
Sample solution is provided at 25 µL, 10mM.
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TDZD-8 is an inhibitor of glycogen synthase kinase-3β (GSK-3β) with IC50 value of 1.4μM [1].
TDZD-8 is a potent inhibitor of GSK-3β. It is found to act as a noncompetitive inhibitor of ATP binding. TDZD-8 is selective against GSK-3β over other protein kinases including PKA, casein kinase II and cyclin dependent kinase 1 (Cdk-1/cyclin B). However, it is also reported that TDZD-8 can inhibit the protein kinase C isoforms PKCβI and PKCδ with IC50 values of 1.4μM and 1.1μM, respectively [1, 2].
In cellular assay, TDZD-8 is found to decrease PDT-induced necrosis of neurons and decrease PDT-induced apoptosis of glial cells through inhibiting GSK-3β as well as PKC. Besides that, TDZD-8 also has anti-leukemia activity in many primary human leukemia cells. It is probably due to its inhibition of PKC and FLT3 [3].
References:
[1] Komandirov M A, Knyazeva E A, Fedorenko Y P, et al. On the role of phosphatidylinositol 3-kinase, protein kinase b/Akt, and glycogen synthase kinase-3β in photodynamic injury of crayfish neurons and glial cells. Journal of Molecular Neuroscience, 2011, 45(2): 229-235.
[2] Martinez A, Alonso M, Castro A, et al. First non-ATP competitive glycogen synthase kinase 3 β (GSK-3β) inhibitors: thiadiazolidinones (TDZD) as potential drugs for the treatment of Alzheimer's disease. Journal of medicinal chemistry, 2002, 45(6): 1292-1299.
[3] Guzman M L, Li X, Corbett C A, et al. Rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1, 2, 4-thiadiazolidine, 3, 5 dione (TDZD-8). Blood, 2007, 110(13): 4436-4444.
Kinase experiment: | GSK-3 activity is assayed in 50 mM Tris-HCl, pH 7.5, 10 mM MgCl2, 1 mM EGTA, and 1 mM EDTA buffer, at 37°C, in the presence of 15 μM GS-1 (substrate), 15 μM [γ-32P]ATP in a final volume of 12 μL. After 20 min incubation at 37°C, 4 μL aliquots of the supernatant are spotted onto 2×2 cm pieces of Whatman P81 phosphocellulose paper, and 20 s later, the filters are washed four times (for at least 10 min each time) in 1% phosphoric acid. The dried filters are transferred into scintillation vials, and the radioactivity is measured in a liquid scintillation counter. Blank values are subtracted, and the GSK-3β activity is expressed in picomoles of phosphate incorporated in GS-1 per 20 min or in percentage of maximal activity[1]. |
Animal experiment: | Apomorphine hydrochloride is administered (0.5 mg/kg). L-dopa (25 mg/kg) plus benserazide-HCl (6.25 mg/kg) are given once-daily. TDZD8, a non-ATP competitive inhibitor of GSK-3β, is dissolved in 10% DMSO and is administered i.p. (TDZD8-L group, 1 mg/kg; TDZD8-H group, 2 mg/kg, respectively) 30 min prior to L-dopa intake for 3 weeks. (±)-1-Phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF38393), a D1 Dopamine receptor agonist, is dissolved in saline and is administered i.p. (SKF38393-L group, 5 mg/kg; SKF38393-H group, 10 mg/kg, respectively) 30 min prior to L-dopa intake for 3 weeks[2]. |
References: [1]. Martinez A, et al. First non-ATP competitive glycogen synthase kinase 3 beta (GSK-3beta) inhibitors: thiadiazolidinones (TDZD) as potential drugs for the treatment of Alzheimer's disease. J Med Chem. 2002 Mar 14;45(6):1292-9. | |
| Cas No. | 327036-89-5 | SDF | |
| 别名 | GSK-3β Inhibitor I; NP 01139 | ||
| 化学名 | 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione | ||
| Canonical SMILES | CN1C(=O)N(C(=O)S1)CC2=CC=CC=C2 | ||
| 分子式 | C10H10N2O2S | 分子量 | 222.26 |
| 溶解度 | ≥ 11.1mg/mL in DMSO | 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 | 4.4992 mL | 22.4962 mL | 44.9924 mL |
| 5 mM | 0.8998 mL | 4.4992 mL | 8.9985 mL |
| 10 mM | 0.4499 mL | 2.2496 mL | 4.4992 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。
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Quality Control & SDS
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- Purity: >99.50%
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