TG003 |
| Catalog No.GC10849 |
TG003 is a racemic compound of (Z)-TG003 and (E)-TG003. (Z)-TG003 is a potent inhibitor of Clk1/Sty; inhibits Clk1 and Clk4 with IC50 values of 20 and 15 nM, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
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 | |
| Chemical Name | (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 | ||
| Formula | C13H15NO2S | M.Wt | 249.33 |
| Solubility | ≥ 12.45mg/mL in DMSO | Storage | Store at -20° C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 35 reference(s) in Google Scholar.)
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