TG003
(Synonyms: 1-(3-乙基-5-甲氧基-2(3H)-苯并噻唑亚基)-2-丙酮) 目录号 : GC10849
Potent inhibitor of CDC 2-like kinase
Cas No.:300801-52-9
Sample solution is provided at 25 µL, 10mM.
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TG003 is a potent and selective inhibitor of Clk-family kinases with IC50 values of 15, 20, 200 nM and >10 μM for mClk4, 1, 2 and 3, respectively [1]. Also, TG003 is also an inhibitor of casein kinase 1 (CK1) [2].
Cdc2-like kinases (Clks) family consist of Clk1, 2, 3 and 4 and play an important role in mRNA splice site selection. Clks phosphorylate serine/arginine-rich proteins that involved in pre-mRNA processing and release them into the nucleoplasm.
TG003 is a potent and selective Clk-family kinases inhibitor. TG003 competed with ATP with Ki value of 0.01 μM on Clk1/Sty. In HeLa cytosolic S100 extract, TG003 inhibited Clk1/Sty-mediated phosphorylation of SF2/ASF, which played an important role in alternative splicing. Also, TG003 inhibited the splicing of β-globin pre-mRNA when complemented with rSF2/ASF. In HA-Clk1/Sty-overexpressing HeLa cells, TG003 (10 μM) reversibly inhibited phosphorylation of SR proteins and caused HA-Clk1/Sty localized in nuclear speckles [1].
In mice, TG003 inhibited the alteration of splicing site selection induced by Clk1/Sty and affected the alternative splicing of endogenous genes. In X. laevis embryo, TG003 (10μM) rescued the morphological abnormalities in the dorsal ectoderm and mesoderm induced by the overexpression of xClk kinase [1].
References:
[1]. Muraki M, Ohkawara B, Hosoya T, et al. Manipulation of alternative splicing by a newly developed inhibitor of Clks. J Biol Chem, 2004, 279(23): 24246-24254.
[2]. Kurihara T, Sakurai E, Toyomoto M, et al. Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors. Mol Pain, 2014, 10: 17.
| Cell experiment [1]: | |
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Cell lines |
HeLa cells |
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Preparation method |
Soluble in DMSO >12.5mg/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 |
2μl of 10 mM TG003 dissolved in Me2SO, final concentration at 10μM, 3 days |
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Applications |
TG003 had a potent inhibitory effect on the activity of Clk1(Cdc2 like kinase1). TG003 inhibited SF2(Splicing factor2) -dependent splicing of β-globin pre-mRNA in vitro by suppression of Clk-mediated phosphorylation. This drug also suppressed serine/arginine-rich protein phosphorylation, dissociation of nuclear speckles, and Clk1-dependent alternative splicing in cells. |
| Animal experiment [2]: | |
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Animal models |
Seven-week-old, male Jcl:TCR mice |
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Dosage form |
30mg/kg TG003 suspended in 5% DMSO, 5% Solutol, 9% Tween-80, and 81% saline，subcutaneously injection |
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Application |
TG003, an inhibitor of CLK1 in mice, could act as a splice-modifying compound for exon-skipping therapy. TG003 promoted skipping of dystrophin exon 31 with the c.4303G > T mutation. |
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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]. Muraki M, Ohkawara B, et al. Manipulation of alternative splicing by a newly developed inhibitor of Clks. J Biol Chem, 2004, 279(23): 24246-24254. [2]. Sako Y1, Ninomiya K1, et al, Development of an orally available inhibitor of CLK1 for skipping a mutated dystrophin exon in Duchenne muscular dystrophy. Sci Rep. 2017 May 30;7:46126. doi: 10.1038/srep46126. |
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| Cas No. | 300801-52-9 | SDF | |
| 别名 | 1-(3-乙基-5-甲氧基-2(3H)-苯并噻唑亚基)-2-丙酮 | ||
| 化学名 | (1Z)-1-(3-ethyl-5-methoxy-1,3-benzothiazol-2-ylidene)propan-2-one | ||
| Canonical SMILES | CCN1C2=C(C=CC(=C2)OC)SC1=CC(=O)C | ||
| 分子式 | C13H15NO2S | 分子量 | 249.33 |
| 溶解度 | ≥ 12.45mg/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 | 4.0107 mL | 20.0537 mL | 40.1075 mL |
| 5 mM | 0.8021 mL | 4.0107 mL | 8.0215 mL |
| 10 mM | 0.4011 mL | 2.0054 mL | 4.0107 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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet