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MedKoo Cat#: 406434 | Name: TG003
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

TG003 is a potent, ATP-competitive inhibitor of Clk-family kinases (IC50 values are 20, 200 and 15 nM for mClk1, 2 and 4 respectively and >10 μ M for mClk3). . TG003 inhibited SF2/ASF-dependent splicing of beta-globin pre-mRNA in vitro by suppression of Clk-mediated phosphorylation. TG003 also suppressed serine/arginine-rich protein phosphorylation, dissociation of nuclear speckles, and Clk1/Sty-dependent alternative splicing in mammalian cells. Consistently, administration of TG003 rescued the embryonic defects induced by excessive Clk activity in Xenopus.

Chemical Structure

TG003
TG003
CAS#719277-26-6

Theoretical Analysis

MedKoo Cat#: 406434

Name: TG003

CAS#: 719277-26-6

Chemical Formula: C13H15NO2S

Exact Mass: 249.0824

Molecular Weight: 249.33

Elemental Analysis: C, 62.62; H, 6.06; N, 5.62; O, 12.83; S, 12.86

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 1,950.00 Ready to ship
1g USD 2,950.00 Ready to ship
2g USD 4,650.00 2 weeks
5g USD 6,950.00 2 weeks
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Related CAS #
300801-52-9 719277-26-6.
Synonym
TG003; TG-003; TG 003.
IUPAC/Chemical Name
(Z)-1-(3-ethyl-5-methoxybenzo[d]thiazol-2(3H)-ylidene)propan-2-one
InChi Key
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 Code
CC(/C=C1SC2=CC=C(OC)C=C2N\1CC)=O
Appearance
white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
        
Biological target:
TG003 is an inhibitor of Clk1/Sty; inhibits Clk1 and Clk4 with IC50 values of 20 and 15 nM, respectively.
In vitro activity:
The effect of TG003 on exon 9 inclusion was dose dependent (Fig. 5c, d). Interestingly, CLK1 and CLK4 were upregulated in the neural lineages compared to iPSCs (Fig. 5e), suggesting that increased activity of these genes might be associated with the misplicing of mutated exon 9. Thus, treatment of SS-NPCs with TG003 increased the amount of FL mRNA of ATR. In line with this observation, the phosphorylation of CHK1 protein in SS-NPCs induced by DNA replication stress was recovered by TG003 treatment (Fig. 5f). Finally, this study investigated whether TG003 could alleviate the abnormal mitosis observed in SS-NPCs. As a result, TG003 successfully increased the frequency of mitotic cells with mitotic spindles of normal morphology (Fig. 5g). Overall, TG003, a CLK1/4 inhibitor, could rescue the missplicing of ATR to alleviate the abnormal mitotic spindle formation in SS-NPCs. Reference: J Hum Genet. 2019; 64(5): 445–458. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075875/
In vivo activity:
Having established that TG003 has a strong effect on PC3 proliferation in vitro, this study tested the effectiveness of TG003 in vivo on PC3 xenografts. This study injected one million cells subcutaneously into the flanks of nude mice. When tumours reached 3 × 3 mm in diameter, a solution of TG003 calculated to give 50 µM final concentration in the mouse was injected intraperitoneally twice a week. After 29 days the untreated tumours reached the maximum permitted size of 12 mm and the experiment was terminated. The TG003 treatments clearly prevented the xenografts growing and the volumes of the tumours in treated animals did not increase (Fig. 5). Other than the clear inhibition of tumour growth, the injection of mice with TG003 bi-weekly did not cause any obvious adverse effects. Reference: Sci Rep. 2021; 11: 7963. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041776/
Solvent mg/mL mM
Solubility
DMSO 28.0 112.18
Ethanol 18.7 75.00
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 249.33 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Ichisima J, Suzuki NM, Samata B, Awaya T, Takahashi J, Hagiwara M, Nakahata T, Saito MK. Verification and rectification of cell type-specific splicing of a Seckel syndrome-associated ATR mutation using iPS cell model. J Hum Genet. 2019 May;64(5):445-458. doi: 10.1038/s10038-019-0574-8. Epub 2019 Mar 8. PMID: 30846821; PMCID: PMC8075875. 2. Uzor S, Zorzou P, Bowler E, Porazinski S, Wilson I, Ladomery M. Autoregulation of the human splice factor kinase CLK1 through exon skipping and intron retention. Gene. 2018 Sep 5;670:46-54. doi: 10.1016/j.gene.2018.05.095. Epub 2018 May 24. PMID: 29802995. 3. Uzor S, Porazinski SR, Li L, Clark B, Ajiro M, Iida K, Hagiwara M, Alqasem AA, Perks CM, Wilson ID, Oltean S, Ladomery MR. CDC2-like (CLK) protein kinase inhibition as a novel targeted therapeutic strategy in prostate cancer. Sci Rep. 2021 Apr 12;11(1):7963. doi: 10.1038/s41598-021-86908-6. PMID: 33846420; PMCID: PMC8041776. 4. Quaresma PG, Weissmann L, Zanotto TM, Santos AC, de Matos AH, Furigo IC, Simabuco FM, Donato J Jr, Bittencourt JC, Lopes-Cendes I, Prada PO. Cdc2-like kinase 2 in the hypothalamus is necessary to maintain energy homeostasis. Int J Obes (Lond). 2017 Feb;41(2):268-278. doi: 10.1038/ijo.2016.174. Epub 2016 Oct 13. PMID: 27733761.
In vitro protocol:
1. Ichisima J, Suzuki NM, Samata B, Awaya T, Takahashi J, Hagiwara M, Nakahata T, Saito MK. Verification and rectification of cell type-specific splicing of a Seckel syndrome-associated ATR mutation using iPS cell model. J Hum Genet. 2019 May;64(5):445-458. doi: 10.1038/s10038-019-0574-8. Epub 2019 Mar 8. PMID: 30846821; PMCID: PMC8075875. 2. Uzor S, Zorzou P, Bowler E, Porazinski S, Wilson I, Ladomery M. Autoregulation of the human splice factor kinase CLK1 through exon skipping and intron retention. Gene. 2018 Sep 5;670:46-54. doi: 10.1016/j.gene.2018.05.095. Epub 2018 May 24. PMID: 29802995.
In vivo protocol:
1. Uzor S, Porazinski SR, Li L, Clark B, Ajiro M, Iida K, Hagiwara M, Alqasem AA, Perks CM, Wilson ID, Oltean S, Ladomery MR. CDC2-like (CLK) protein kinase inhibition as a novel targeted therapeutic strategy in prostate cancer. Sci Rep. 2021 Apr 12;11(1):7963. doi: 10.1038/s41598-021-86908-6. PMID: 33846420; PMCID: PMC8041776. 2. Quaresma PG, Weissmann L, Zanotto TM, Santos AC, de Matos AH, Furigo IC, Simabuco FM, Donato J Jr, Bittencourt JC, Lopes-Cendes I, Prada PO. Cdc2-like kinase 2 in the hypothalamus is necessary to maintain energy homeostasis. Int J Obes (Lond). 2017 Feb;41(2):268-278. doi: 10.1038/ijo.2016.174. Epub 2016 Oct 13. PMID: 27733761.
1: Ţînţaş ML, Peauger L, Alix F, Papamicaël C, Besson T, Sopková-de Oliveira Santos J, Gembus V, Levacher V. Straightforward Access to a New Class of Dual DYRK1A/CLK1 Inhibitors Possessing a Simple Dihydroquinoline Core. Molecules. 2022 Dec 21;28(1):36. doi: 10.3390/molecules28010036. PMID: 36615235; PMCID: PMC9822041. 2: Lebecque B, Bourgne C, Munje C, Berger J, Tassin T, Cony-Makhoul P, Guerci- Bresler A, Johnson-Ansah H, Liu W, Saugues S, Tchirkov A, Vetrie D, Copland M, Berger MG. The Spliceosome: A New Therapeutic Target in Chronic Myeloid Leukaemia. Cancers (Basel). 2022 Sep 27;14(19):4695. doi: 10.3390/cancers14194695. PMID: 36230624; PMCID: PMC9563771. 3: Patel A, Dobbins T, Kong X, Patel R, Carter G, Harding L, Sparks RP, Patel NA, Cooper DR. Induction of beige-like adipocyte markers and functions in 3T3-L1 cells by Clk1 and PKCβII inhibitory molecules. J Cell Mol Med. 2022 Aug;26(15):4183-4194. doi: 10.1111/jcmm.17345. Epub 2022 Jul 8. PMID: 35801494; PMCID: PMC9344812. 4: Abe I, Tanaka T, Ohe K, Fujii H, Nagata M, Ochi K, Senda Y, Takeshita K, Koga M, Kudo T, Enjoji M, Yanase T, Kobayashi K. Inhibition of NR5A1 Phosphorylation Alleviates a Transcriptional Suppression Defect Caused by a Novel NR0B1 Mutation. J Endocr Soc. 2022 Apr 22;6(6):bvac068. doi: 10.1210/jendso/bvac068. PMID: 35592512; PMCID: PMC9113462. 5: Carrillo García C, Becker C, Forster M, Lohmann S, Freitag P, Laufer S, Sievers S, Fleischmann BK, Hesse M, Schade D. High-Throughput Screening Platform in Postnatal Heart Cells and Chemical Probe Toolbox to Assess Cardiomyocyte Proliferation. J Med Chem. 2022 Jan 27;65(2):1505-1524. doi: 10.1021/acs.jmedchem.1c01173. Epub 2021 Nov 24. PMID: 34818008. 6: Uzor S, Porazinski SR, Li L, Clark B, Ajiro M, Iida K, Hagiwara M, Alqasem AA, Perks CM, Wilson ID, Oltean S, Ladomery MR. CDC2-like (CLK) protein kinase inhibition as a novel targeted therapeutic strategy in prostate cancer. Sci Rep. 2021 Apr 12;11(1):7963. doi: 10.1038/s41598-021-86908-6. PMID: 33846420; PMCID: PMC8041776. 7: Shibata S, Ajiro M, Hagiwara M. Mechanism-Based Personalized Medicine for Cystic Fibrosis by Suppressing Pseudo Exon Inclusion. Cell Chem Biol. 2020 Dec 17;27(12):1472-1482.e6. doi: 10.1016/j.chembiol.2020.08.013. Epub 2020 Sep 8. PMID: 32905759. 8: Babu N, Pinto SM, Biswas M, Subbannayya T, Rajappa M, Mohan SV, Advani J, Rajagopalan P, Sathe G, Syed N, Radhakrishna VD, Muthusamy O, Navani S, Kumar RV, Gopisetty G, Rajkumar T, Radhakrishnan P, Thiyagarajan S, Pandey A, Gowda H, Majumder P, Chatterjee A. Phosphoproteomic analysis identifies CLK1 as a novel therapeutic target in gastric cancer. Gastric Cancer. 2020 Sep;23(5):796-810. doi: 10.1007/s10120-020-01062-8. Epub 2020 Apr 24. PMID: 32333232. 9: Zaslavsky K, Zhang WB, McCready FP, Rodrigues DC, Deneault E, Loo C, Zhao M, Ross PJ, El Hajjar J, Romm A, Thompson T, Piekna A, Wei W, Wang Z, Khattak S, Mufteev M, Pasceri P, Scherer SW, Salter MW, Ellis J. SHANK2 mutations associated with autism spectrum disorder cause hyperconnectivity of human neurons. Nat Neurosci. 2019 Apr;22(4):556-564. doi: 10.1038/s41593-019-0365-8. Epub 2019 Mar 25. PMID: 30911184; PMCID: PMC6475597. 10: Ichisima J, Suzuki NM, Samata B, Awaya T, Takahashi J, Hagiwara M, Nakahata T, Saito MK. Verification and rectification of cell type-specific splicing of a Seckel syndrome-associated ATR mutation using iPS cell model. J Hum Genet. 2019 May;64(5):445-458. doi: 10.1038/s10038-019-0574-8. Epub 2019 Mar 8. PMID: 30846821; PMCID: PMC8075875. 11: Kallen J, Bergsdorf C, Arnaud B, Bernhard M, Brichet M, Cobos-Correa A, Elhajouji A, Freuler F, Galimberti I, Guibourdenche C, Haenni S, Holzinger S, Hunziker J, Izaac A, Kaufmann M, Leder L, Martus HJ, von Matt P, Polyakov V, Roethlisberger P, Roma G, Stiefl N, Uteng M, Lerchner A. X-ray Structures and Feasibility Assessment of CLK2 Inhibitors for Phelan-McDermid Syndrome. ChemMedChem. 2018 Sep 19;13(18):1997-2007. doi: 10.1002/cmdc.201800344. Epub 2018 Aug 16. PMID: 29985556. 12: Uzor S, Zorzou P, Bowler E, Porazinski S, Wilson I, Ladomery M. Autoregulation of the human splice factor kinase CLK1 through exon skipping and intron retention. Gene. 2018 Sep 5;670:46-54. doi: 10.1016/j.gene.2018.05.095. Epub 2018 May 24. PMID: 29802995. 13: Bowler E, Porazinski S, Uzor S, Thibault P, Durand M, Lapointe E, Rouschop KMA, Hancock J, Wilson I, Ladomery M. Hypoxia leads to significant changes in alternative splicing and elevated expression of CLK splice factor kinases in PC3 prostate cancer cells. BMC Cancer. 2018 Apr 2;18(1):355. doi: 10.1186/s12885-018-4227-7. PMID: 29606096; PMCID: PMC5879922. 14: Sako Y, Ninomiya K, Okuno Y, Toyomoto M, Nishida A, Koike Y, Ohe K, Kii I, Yoshida S, Hashimoto N, Hosoya T, Matsuo M, Hagiwara M. 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. PMID: 28555643; PMCID: PMC5448077. 15: Quaresma PG, Weissmann L, Zanotto TM, Santos AC, de Matos AH, Furigo IC, Simabuco FM, Donato J Jr, Bittencourt JC, Lopes-Cendes I, Prada PO. Cdc2-like kinase 2 in the hypothalamus is necessary to maintain energy homeostasis. Int J Obes (Lond). 2017 Feb;41(2):268-278. doi: 10.1038/ijo.2016.174. Epub 2016 Oct 13. PMID: 27733761. 16: Nishida A, Oda A, Takeuchi A, Lee T, Awano H, Hashimoto N, Takeshima Y, Matsuo M. Staurosporine allows dystrophin expression by skipping of nonsense- encoding exon. Brain Dev. 2016 Sep;38(8):738-45. doi: 10.1016/j.braindev.2016.03.003. Epub 2016 Mar 25. PMID: 27021413. 17: Sakuma M, Iida K, Hagiwara M. Deciphering targeting rules of splicing modulator compounds: case of TG003. BMC Mol Biol. 2015 Sep 24;16:16. doi: 10.1186/s12867-015-0044-6. PMID: 26400733; PMCID: PMC4580995. 18: Foucourt A, Hédou D, Dubouilh-Benard C, Girard A, Taverne T, Casagrande AS, Désiré L, Leblond B, Besson T. Design and synthesis of thiazolo[5,4-f]quinazolines as DYRK1A inhibitors, part II. Molecules. 2014 Sep 26;19(10):15411-39. doi: 10.3390/molecules191015411. PMID: 25264830; PMCID: PMC6271009. 19: Marcel V, Fernandes K, Terrier O, Lane DP, Bourdon JC. Modulation of p53β and p53γ expression by regulating the alternative splicing of TP53 gene modifies cellular response. Cell Death Differ. 2014 Sep;21(9):1377-87. doi: 10.1038/cdd.2014.73. Epub 2014 Jun 13. PMID: 24926616; PMCID: PMC4131182. 20: Kim H, Choi K, Kang H, Lee SY, Chi SW, Lee MS, Song J, Im D, Choi Y, Cho S. Identification of a novel function of CX-4945 as a splicing regulator. PLoS One. 2014 Apr 17;9(4):e94978. doi: 10.1371/journal.pone.0094978. PMID: 24743259; PMCID: PMC3990583.