| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
CLK2 0.096 nM (Kd) CLK4 0.61 nM (Kd) CLK1 4.8 nM (Kd) CLK3 6.5 nM (Kd) DYRK1A 0.074 nM (Kd) DYRK1B 1.5 nM (Kd) DYRK2 32 nM (Kd)
T025 targets Cdc2-like kinases (CLK1-4), which are key regulators of alternative splicing. It binds to these kinases with high affinity, with Kd values ranging from 0.096 nM for CLK2 to 6.5 nM for CLK3. By inhibiting CLK activity, T025 reduces CLK-dependent phosphorylation and modulates splicing events, leading to antiproliferative effects in cancer cells. |
|---|---|
| ln Vitro |
In a dose-dependent manner, T025 (0-1000 nM; 72 hours) strongly reduces the proliferation of MDA-MB-468 cells[1]. Phosphorylation levels in MDA-MB-468 cells are decreased by T025 (0-1000 nM; 6 hours)[1].
In vitro, T025 shows potent antiproliferative activity in both hematological and solid cancer cell lines, with IC50 values ranging from 30 to 300 nM. It induces caspase-3/7-mediated apoptosis and reduces CLK-dependent phosphorylation. These effects are consistent with the compound's mechanism of action as a CLK inhibitor, which disrupts splicing and induces cell death in cancer cells. |
| ln Vivo |
T025 (50 mg/kg; po; 2, 4, 8 hours) suppresses the phosphorylation of CLK-dependent genes and causes exon skipping in a variety of genes in Balb/c nude mice (7 to 8 week old females)[1]. T025 (50 mg/kg; po; twice daily on two days per week, for three weeks) reduces the formation of tumors in MDA-MB-468 xenograft mice without affecting body weight in Balb/c nude mice (seven to eight week old females) [1].
In vivo data for T025 are limited. As an orally available CLK inhibitor, it is expected to have good oral bioavailability and be suitable for in vivo studies. However, specific in vivo studies have not been detailed in the available literature. Further research is needed to evaluate its efficacy and safety in animal models. |
| Enzyme Assay |
The in vitro binding assay for T025 typically involves measuring its affinity for CLK1-4 using surface plasmon resonance (SPR) or similar biophysical techniques. Kd values are determined to quantify the binding affinity. Kinase activity assays are also used to measure the compound's inhibitory activity against CLKs. These assays confirm its potency and selectivity.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: MDA-MB-468 cells Tested Concentrations: 1, 10, 100 and 1000 nM Incubation Duration: 72 hrs (hours) Experimental Results: Resulted in concentration dependent growth inhibition. Western Blot Analysis[1] Cell Types: MDA-MB-468 cells Tested Concentrations: 0, 10, 30, 100, 300 and 1000 nM Incubation Duration: 6 hrs (hours) Experimental Results: diminished both pCLK2 and CLK2. Cellular assays for T025 are performed using various cancer cell lines. Cells are treated with varying concentrations of the compound, and cell viability is assessed to determine IC50 values. Apoptosis is measured by caspase-3/7 activation assays. The compound's ability to reduce CLK-dependent phosphorylation is confirmed by Western blotting. |
| Animal Protocol |
Animal/Disease Models: Balb/c nude mice (7 to 8 week-old females)[1]
Doses: 50 mg/kg Route of Administration: Oral administration; 2, 4, 8 hrs (hours). Experimental Results: pCLK2 detected with immunohistochemistry and immunoblotting diminished, by a reduction in the RPS6KB1 exon 7 and BCLAF1 exon 11 percentage splice-in (PSI) values. Animal/Disease Models: Balb/c nude mice ( 7 to 8 week-old females)[1] Doses: 50 mg/kg Route of Administration: Oral administration; twice (two times) daily on 2 days per week, for 3 weeks. Experimental Results: Suppressed tumor growth and < 10% nadir body weight loss. In vivo animal protocols for T025 are not available in the literature. As an orally available CLK inhibitor, it would typically be evaluated in mouse xenograft models of cancer. However, such studies have not been reported. The compound is currently used primarily for in vitro research. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of T025 are not fully characterized. It is an orally available compound, suggesting sufficient oral bioavailability. The compound is typically dissolved in DMSO for in vitro studies. Further studies are needed to determine its half-life, clearance, and volume of distribution.
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| Toxicity/Toxicokinetics |
Toxicity data for T025 are limited. As a CLK inhibitor, it may have on-target toxicities related to the essential role of CLKs in normal splicing. The compound is intended for research use only and is not approved for human therapeutic use. Comprehensive toxicological studies are needed.
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| References | |
| Additional Infomation |
T025 is a potent and orally available inhibitor of Cdc2-like kinases (CLK1-4). It induces apoptosis and shows antiproliferative activity in cancer cell lines. The compound is not currently in clinical trials and is used as a research tool for studying CLK biology and cancer therapy.
|
| Molecular Formula |
C21H18N8
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|---|---|
| Molecular Weight |
382.42122220993
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| Exact Mass |
382.165
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| CAS # |
2407433-00-3
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| PubChem CID |
133082038
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| Appearance |
Yellow to green solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
527
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
N1C=C(C2C=CC3C(=CC=CN=3)C=2)C2=C(N=C(NC)N=C12)NCC1N=CC=CN=1
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| InChi Key |
PMWVYONICYRLNY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H18N8/c1-22-21-28-19-18(20(29-21)27-12-17-24-8-3-9-25-17)15(11-26-19)13-5-6-16-14(10-13)4-2-7-23-16/h2-11H,12H2,1H3,(H3,22,26,27,28,29)
|
| Chemical Name |
2-N-methyl-4-N-(pyrimidin-2-ylmethyl)-5-quinolin-6-yl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 8.25 mg/mL (21.57 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 10 mg/mL (26.15 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6149 mL | 13.0746 mL | 26.1493 mL | |
| 5 mM | 0.5230 mL | 2.6149 mL | 5.2299 mL | |
| 10 mM | 0.2615 mL | 1.3075 mL | 2.6149 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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