(E/Z)-TG003

製品コードS7320 バッチS732001

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₃H₁₅NO₂S

分子量

249.33

CAS No.

300801-52-9

Solubility (25°C)*

体外

DMSO (warmed with 50ºC water bath)

50 mg/mL (200.53 mM)

Ethanol

50 mg/mL (200.53 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	3.000mg/ml (12.03mM)	Taking the 1 mL working solution as an example, add 50 μL of 60 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	3.000mg/ml (12.03mM)	Taking the 1 mL working solution as an example, add 50 μL of 60 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	(E/Z)-TG003 is a potent and ATP-competitive Cdc2-like kinase (Clk) inhibitor with IC50 of 20 nM, 200 nM, and 15 nM for Clk1, Clk2, and Clk4, respectively. No inhibitory effect on Clk3, SRPK1, SRPK2, or PKC.
in vitro	TG003 inhibits SF2/ASF-dependent splicing of human β-globin in vitro by suppression of Clk1/Sty-mediated phosphorylation. TG003 inhibits Clk1/Sty kinase activity in mammalian cells, while has no toxic effect on growth of HeLa and COS-7 cells at 10 μM concentration. ^[1] TG003 blocks IL-1β RNA production by platelets by inhibiting splicing of IL-1β heteronuclear RNA. ^[2] During 3T3-L1 adipocyte differentiation, TG003 also blocks alternative splicing of PKCβII and expression of PPARγ1 and PPARγ2. ^[3]
in vivo	TG003 (10 μM) rescues the embryonic defects induced by excessive Clk activity in Xenopus. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	In Vitro Kinase Assay
キナーゼアッセイ	Kinase activity of Clks and SRPKs is assayed in a reaction mixture, containing 200 mM Tris-HCl (pH 7.5), 12.5 mM MgCl₂, 8 mM dithiothreitol, 4 mM EGTA, 1–20 μM ATP, 1 μCi of [γ-³²P]ATP, 1 μg of synthetic peptide of SF2/ASF RS domain (NH2-RSPSYGRSRSRSRSRSRSRSRSNSRSRSY-OH), and 0.1–1 μg of purified kinases in a final volume of 40 μL. cAMP-dependent protein kinase activity is assayed in a reaction mixture containing 80 mM Tris-HCl (pH 7.5), 12.5 mM MgCl₂, 8 mM dithiothreitol, 4 mM EGTA, 10 μM ATP, 1 μCi of [γ-³²P]ATP, 5 μg of histone H1, and 1 μg of catalytic subunit of rat cAMP-dependent protein kinase purified. Protein kinase C activity is assayed in a reaction mixture containing 200 mM Tris-HCl (pH 7.5), 12.5 mM MgCl₂, 1 mM CaCl₂, 80 μg/mL phosphatidylserine, 8 μg/mL diolein, 10 μM ATP, 1 μCi of [γ-³²P]ATP, 5 μg of histone H1, and 2 μL of partially purified rat protein kinase C. The final concentration of Me₂SO is adjusted to 1% regardless of inhibitor concentration. The reaction mixture is incubated at 30 or 25 °C for mammalian or Xenopus recombinant proteins, respectively, for 10 min, and a half-portion is spotted on P81 phosphocellulose membrane. The kinase assay conditions, including the incubation period and concentration of kinases and substrates, are optimized to maintain the linearity during incubation. The membrane is washed with 5% phosphoric acid solution (SF2/ASF RS domain) or 5% trichloroacetic solution (histone H1) at least over 15 min. The radioactivity is measured using a liquid scintillation counter. The net radioactivity is deduced by subtracting the background count from the reaction mixture without kinase, and the data are expressed as the percentage to the control sample containing the solvent.
細胞アッセイ	細胞株	HeLa cells and COS-7 cells
	濃度	~10 μM
	反応時間	3 days
	実験の流れ	2 × 10⁵ HeLa cells or 1.5 × 10⁵ COS-7 cells resuspended in 2 mL of medium are plated on 6-well dishes, and 2 μL of 10 mM TG003 dissolved in Me₂SO (final concentration at 10 μM), or 2 μL of Me₂SO, is added to some wells. Cells are trypsinized, and the density is counted every 24 h for 3 days. Cells are then fixed with 1 mL of ice-cold 70% ethanol, washed with PBS, incubated in 1 ml of PBS containing 1 μg/mL DNase-free RNase A and 50 μg/mL propidium iodide for 20 min at 37 °C, and proceeded to cell cycle analysis by FACSCalibur.
動物実験	動物モデル	Xenopus laevis embryos
	投薬量	~10 μM
	投与方法	--

参考

https://pubmed.ncbi.nlm.nih.gov/15010457/
https://pubmed.ncbi.nlm.nih.gov/21430222/
https://pubmed.ncbi.nlm.nih.gov/23308182/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Combined therapy with DR5-targeting antibody-drug conjugate and CDK inhibitors as a strategy for advanced colorectal cancer [ Cell Rep Med, 2025, S2666-3791(25)00231-9]	PubMed: 40449480
A common cellular response to broad splicing perturbations is characterized by metabolic transcript downregulation driven by the Mdm2-p53 axis [ Dis Model Mech, 2024, 17(2)dmm050356]	PubMed: 38426258
The Spliceosome: A New Therapeutic Target in Chronic Myeloid Leukaemia [ Cancers (Basel), 2022, 14(19)4695]	PubMed: 36230624
Proteasome Inhibitor-Induced Modulation Reveals the Spliceosome as a Specific Therapeutic Vulnerability in Multiple Myeloma [ Nat Commun, 2020, 22;11(1):1931]	PubMed: 32321912
Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2 [ Mol Cell, 2020, 80(6):1104-1122.e9]	PubMed: 33259812
Phosphoproteomic analysis identifies CLK1 as a novel therapeutic target in gastric cancer. [ Gastric Cancer, 2020, 24]	PubMed: 32333232
Integrated phosphoproteomics and transcriptional classifiers reveal hidden RAS signaling dynamics in multiple myeloma. [ Blood Adv, 2019, 3(21):3214-3227]	PubMed: 31698452
Chemically defined and growth-factor-free culture system for the expansion and derivation of human pluripotent stem cells. [ Nat Biomed Eng, 2018, 2(3):173-182]	PubMed: 31015717
Identification of nonsense-mediated mRNA decay pathway as a critical regulator of p53 isoform β [ Sci Rep, 2017, 7(1):17535]	PubMed: 29235495

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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