| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
CLK1-IN-1 targets Cdc2-like kinase 1 (CLK1), a dual-specificity kinase that plays a critical role in the regulation of alternative splicing by phosphorylating serine/arginine-rich (SR) proteins. By inhibiting CLK1 with high potency (IC₅0 = 2 nM), the compound modulates RNA splicing and gene expression. CLK1 is involved in cell cycle progression and is a potential therapeutic target in cancer. The compound's high selectivity makes it a valuable tool for studying CLK1 biology.
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| ln Vitro |
The strongest inhibitory kinase is CLK1 (IC50: 2 nM). With the exception of CLK1, only two kinases have IC50 values less than 100 nM: CLK2 (IC50: 31 nM) and CLK4 (IC50: 8 nM). DYRK1A has the strongest off-target of all the kinases. It was also investigated whether CLK1-IN-1 could cause autophagy in human ovarian cancer cell lines, BNL CL.2 and SKOV-3. A clear dose dependence was observed in the impact of CLK1-IN-1 on yellow LC3 spots, with the maximum effect observed at a dose of 10 μM. Additionally, compared to cells treated with DMSO, the number of red LC3 puncta (mRFP signal 35 only) increased in cells treated with CLK1-IN-1, indicating the formation of autolysosomes. Crucially, CLK1-IN-1 promotes SQSTM1/p62 degradation and raises the ratio of red to yellow LC3 dots, both of which show that autophagic flux is induced by CLK1-IN-1 [1].
In vitro, CLK1-IN-1 is a potent and selective inhibitor of Cdc2-like kinase 1 (CLK1) with an IC₅0 of 2 nM. It is the most potently inhibited kinase among those tested, indicating high selectivity. By inhibiting CLK1, the compound modulates the phosphorylation of SR proteins, thereby affecting alternative splicing. Its potent and selective activity makes it a valuable tool for studying CLK1-dependent splicing events and their role in cellular function and disease. |
| ln Vivo |
When exposed to APAP, the liver is severely injured; however, when treated with CLK1-IN-1 (ip, 30 mg/kg), the liver is significantly protected. The two labeling enzymes were returned to normal levels after therapy with CLK1-IN-1, according to the results [1]. This was achieved by dramatically lowering blood ALT and AST levels.
In vivo studies of CLK1-IN-1 are limited, as it is primarily used as a research tool in cellular assays. However, given its potent and selective inhibition of CLK1 with an IC₅0 of 2 nM, the compound may have potential for in vivo efficacy studies in animal models of diseases where CLK1 plays a role, such as cancer. Further studies are needed to evaluate its pharmacokinetic properties, bioavailability, and efficacy in vivo. |
| Enzyme Assay |
For in vitro enzyme/receptor binding assays, CLK1-IN-1 can be evaluated using kinase activity assays that measure CLK1-mediated phosphorylation. The compound is incubated with recombinant CLK1 kinase and ATP at various concentrations. Kinase activity is quantified by measuring phosphorylation of peptide substrates using radiometric, fluorescence-based, or ELISA methods. IC₅0 values are determined from dose-response curves. Selectivity profiling against other kinases is performed to confirm specificity.
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| Cell Assay |
For in vitro cellular experiments, CLK1-IN-1 is tested in cell lines to evaluate its effects on CLK1 activity and alternative splicing. Cells are cultured in appropriate media and treated with various concentrations of the compound. CLK1 activity is assessed by measuring the phosphorylation of SR proteins using Western blotting. Changes in alternative splicing are analyzed by RT-PCR or RNA sequencing. Cell viability and proliferation are monitored using standard assays.
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| Animal Protocol |
For in vivo animal experiments, CLK1-IN-1 can be administered to animals via various routes, including oral gavage, intravenous injection, or intraperitoneal injection. The compound's efficacy can be evaluated in tumor models or other disease models where CLK1 plays a role. Typical dosing regimens may range from 1 to 50 mg/kg. Pharmacodynamic markers, such as SR protein phosphorylation and splicing changes, are measured in tissues. Tumor volume, body weight, and overall health are monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of CLK1-IN-1 are not extensively detailed in the provided references. As a small molecule with a molecular weight of 409.42, it may have reasonable oral bioavailability and tissue distribution. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies. The compound's metabolism and excretion pathways remain to be fully characterized.
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| Toxicity/Toxicokinetics |
Toxicological data for CLK1-IN-1 are limited, as it is primarily a research tool. As a CLK1 inhibitor, its toxicity would depend on the importance of CLK1 for normal cellular function. Comprehensive toxicology studies including acute and repeated-dose toxicity, genotoxicity, and cardiotoxicity assessments would be needed for further development. Appropriate safety precautions should be taken when handling this compound.
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| References | |
| Additional Infomation |
CLK1-IN-1 is a research compound used to study CLK1 biology and its role in RNA splicing and cancer. No clinical trials or regulatory approvals have been reported for this compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is a potent and selective CLK1 inhibitor with an IC₅0 of 2 nM.
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| Molecular Formula |
C24H16FN5O
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| Molecular Weight |
409.415147781372
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| Exact Mass |
409.133
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| CAS # |
2123491-32-5
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| PubChem CID |
129318964
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| Appearance |
White to off-white solid powder
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| LogP |
4.9
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
31
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| Complexity |
631
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC1C=CC(=CC=1)[C@H](C)N1C2C(=CN=C3C=CC(C4C=CC5=C(C=4)N=CO5)=CC=23)N=N1
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| InChi Key |
BHKVSOQUPYXVRZ-AWEZNQCLSA-N
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| InChi Code |
InChI=1S/C24H16FN5O/c1-14(15-2-6-18(25)7-3-15)30-24-19-10-16(4-8-20(19)26-12-22(24)28-29-30)17-5-9-23-21(11-17)27-13-31-23/h2-14H,1H3/t14-/m0/s1
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| Chemical Name |
5-[1-[(1S)-1-(4-fluorophenyl)ethyl]triazolo[4,5-c]quinolin-8-yl]-1,3-benzoxazole
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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 : ~25 mg/mL (~61.06 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4425 mL | 12.2124 mL | 24.4248 mL | |
| 5 mM | 0.4885 mL | 2.4425 mL | 4.8850 mL | |
| 10 mM | 0.2442 mL | 1.2212 mL | 2.4425 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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