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CDK&Aurora kinase

TG003 (300801-52-9)

TG003 is a potent, specific, reversible, and ATP competitive inhibitor of Cdc2 like kinase(Clk).

Not Intended for Therapeutic Use. For research use only.

CAS: 300801-52-9 Category

TG003 (300801-52-9) Description

TG003  is potent, specific, reversible, and ATP-competitive inhibitor of Cdc2-like kinase (Clk). Ki = 10 nM for mClk1/Sty; IC50 = 15 nM, 20 nM, 200 nM, and > 10 mM for mClk4, mClk1, mClk2, and mClk3, respectively.

TG003 regulates alternative splicing and reduces the phosphorylation of SF2/ASF1.

TG003 has been used to develop assays for screening substances that affect mRNA splicing

Cdc2-like kinase (Clk), among a number of other kinases, phosphorylates serine/arginine-rich proteins which play a role in alternative splicing of pre-mRNA. The Clk family consists of four members, which include Clk1/Sty and Clk2-4. TG003 is a novel benzothiazole compound that demonstrates potent inhibition of Clk1/Sty and Clk4 with IC50 values of 20 and 15 nM, respectively.1 TG003 exhibits considerably weaker inhibition of Clk2 and Clk3 (IC50 = 200 nM and >10 μM, respectively).1 Through suppression of Clk-mediated phosphorylation, TG003 inhibits SF2/ASF-dependent splicing of β-globin pre-mRNA at 1 μM in vitro.1 At 10 μM, TG003 rescues the embryonic defects induced by excessive Clk activity in Xenopus.

TG003 (300801-52-9) Specifications

Product Name TG003
Synonyms TG003; 300801-52-9; TG 003; Cdc2-Like Kinase Inhibitor, TG003; TG-003

 

Chemical Name (1Z)-1-(3-Ethyl-5-methoxy-1,3-benzothiazol-2-ylidene)propan-2-one
Drug Class Cdc2-Like Kinase Inhibitor;Clk inhibitor
Purity >98%
CAS Number 300801-52-9
Molecular Formula C13H15NO2S
Molecular Weight 249.328 g/mol
Monoisotopic Mass 249.082 g/mol
MDL number MFCD00624584
InChIKey BGVLELSCIHASRV-QPEQYQDCSA-N
InChi Code InChI=1S/C13H15NO2S/c1-4-14-11-8-10(16-3)5-6-12(11)17-13(14)7-9(2)15/h5-8H,4H2,1-3H3/b13-7-
SMILES CC(/C=C1SC2=CC=C(OC)C=C2N\1CC)=O
Form white solid powder
Color white to beige
Solubility  Soluble in DMSO, not in water
Storage Temp.  0 – 4 C for short term (days to weeks), or -20 C for long term (months).
Shelf life >2 years if stored properly
Handling Dry, dark and at 0 – 4 C for short term (days to weeks) or -20 C for long term (months to years).
Application TG003 has been used to develop assays for screening substances that affect mRNA splicing

 


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RIDADR NONH for all modes of transport

References:

  1. Li P, Carter G, Romero J, Gower KM, Watson J, Patel NA, Cooper DR. Clk/STY (cdc2-like kinase 1) and Akt regulate alternative splicing and adipogenesis in 3T3-L1 pre-adipocytes. PLoS One. 2013;8(1):e53268. doi: 10.1371/journal.pone.0053268. Epub 2013 Jan 4. PubMed PMID: 23308182; PubMed Central PMCID: PMC3537621.
  2. Ninomiya K, Kataoka N, Hagiwara M. Stress-responsive maturation of Clk1/4 pre-mRNAs promotes phosphorylation of SR splicing factor. J Cell Biol. 2011 Oct 3;195(1):27-40. doi: 10.1083/jcb.201107093. Epub 2011 Sep 26. PubMed PMID: 21949414; PubMed Central PMCID: PMC3187705.
  3. Nishida A, Kataoka N, Takeshima Y, Yagi M, Awano H, Ota M, Itoh K, Hagiwara M, Matsuo M. Chemical treatment enhances skipping of a mutated exon in the dystrophin gene. Nat Commun. 2011;2:308. doi: 10.1038/ncomms1306. PubMed PMID: 21556062; PubMed Central PMCID: PMC3113229.
  4. Rosenthal AS, Tanega C, Shen M, Mott BT, Bougie JM, Nguyen DT, Misteli T, Auld DS, Maloney DJ, Thomas CJ. Potent and selective small molecule inhibitors of specific isoforms of Cdc2-like kinases (Clk) and dual specificity tyrosine-phosphorylation-regulated kinases (Dyrk). Bioorg Med Chem Lett. 2011 May 15;21(10):3152-8. doi: 10.1016/j.bmcl.2011.02.114. Epub 2011 Mar 4. PubMed PMID: 21450467; PubMed Central PMCID: PMC3085634.
  5. James BP, Staatz WD, Wilkinson ST, Meuillet E, Powis G. Superoxide dismutase is regulated by LAMMER kinase in Drosophila and human cells. Free Radic Biol Med. 2009 Mar 15;46(6):821-7. doi: 10.1016/j.freeradbiomed.2008.12.012. Epub 2008 Dec 24. PubMed PMID: 19135146; PubMed Central PMCID: PMC2699669.
  6. Yomoda J, Muraki M, Kataoka N, Hosoya T, Suzuki M, Hagiwara M, Kimura H. Combination of Clk family kinase and SRp75 modulates alternative splicing of Adenovirus E1A. Genes Cells. 2008 Mar;13(3):233-44. doi: 10.1111/j.1365-2443.2008.01163.x. PubMed PMID: 18298798.
  7. Muraki M, Ohkawara B, Hosoya T, Onogi H, Koizumi J, Koizumi T, Sumi K, Yomoda J, Murray MV, Kimura H, Furuichi K, Shibuya H, Krainer AR, Suzuki M, Hagiwara M. Manipulation of alternative splicing by a newly developed inhibitor of Clks. J Biol Chem. 2004 Jun 4;279(23):24246-54. Epub 2004 Mar 8. PubMed PMID: 15010457.