| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
The primary targets of KH-CB19 are CLK1 (cdc2-like kinase 1) and CLK4 (cdc2-like kinase 4). It is a potent CLK inhibitor with CLK1 IC50 of 19.7 nM and CLK3 IC50 of 530 nM. KH-CB19 is a potent, non-ATP mimetic binding and reversible inhibitor of Clk1 and Dyk1A with excellent selectivity over Clk3 and against 71-kinases. CLK kinases are involved in the regulation of alternative splicing and gene expression. By inhibiting CLK1 and CLK4, KH-CB19 can modulate splicing and gene expression programs, potentially affecting cancer cell survival and viral replication.
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| ln Vitro |
Human microvascular endothelial cells treated with KH-CB19 (10 μM; 1 h) exhibit the inhibitory action of CLK on SR protein phosphorylation [1]. In A549 cells, KH-CB19 (50 μM; 6 hours) suppresses CLK4 destruction [2].
KH-CB19 is a potent CLK inhibitor with CLK1 IC50 of 19.7 nM and CLK3 IC50 of 530 nM. It shows antiviral activity and inhibits influenza virus replication with an IC50 of 13.6 µM. The compound suppresses serine/arginine-rich protein phosphorylation by CLKs under proinflammatory conditions. Its excellent selectivity over Clk3 and against 71-kinases suggests a favorable specificity profile. The compound's antiviral activity indicates potential applications in treating viral infections, particularly influenza. |
| ln Vivo |
No specific in vivo activity data is publicly available for KH-CB19. As a CLK inhibitor, it would be expected to have effects on splicing and gene expression in vivo. The compound's antiviral activity suggests potential efficacy in animal models of influenza infection. Its potential applications in cancer and transcription-dependent diseases would require evaluation in appropriate in vivo models. However, specific in vivo studies have not been detailed in the available literature.
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| Enzyme Assay |
No specific non-cell assay protocol is available for KH-CB19. For CLK inhibitors, standard cell-free assays use recombinant CLK enzymes and peptide substrates. The compound is incubated with the enzyme and substrate, and kinase activity is measured by phosphorylation of the substrate using radioactive ATP or fluorescent detection methods. These assays provide quantitative data on the compound's potency (IC50) against various CLK isoforms and selectivity over other kinases.
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| Cell Assay |
Western blot analysis[1]
Cell Types: Human microvascular endothelial cells (HMEC-1) Tested Concentrations: 10 μM Incubation Duration: 1 hour Experimental Results: Phosphorylation of SRp75, SRp55 and SRp20 was diminished compared to non-TNF-α stimulated controls. The TNF-α-induced increase in phosphorylation was diminished for all analyzed SR proteins compared with TNF-α-stimulated controls. No specific cell-based assay protocol is available for KH-CB19. For CLK inhibitors, standard cellular assays involve treatment of cells with the compound and measurement of CLK target phosphorylation by western blot. Splicing assays can be performed to assess the compound's effects on alternative splicing of CLK-regulated genes. For antiviral studies, influenza virus-infected cells are treated with KH-CB19, and viral replication is measured by plaque assay or qPCR. Cell viability assays can be performed to assess cytotoxicity. |
| Animal Protocol |
No specific animal protocol is available for KH-CB19. For antiviral studies, standard in vivo models include influenza virus infection in mice. KH-CB19 is administered (route and dose to be determined) prior to or following viral infection. Viral titers, lung pathology, and survival are assessed. For cancer studies, xenograft models using cancer cell lines sensitive to CLK inhibition could be employed. The compound's effects on tumor growth and survival would be evaluated.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is publicly available for KH-CB19. The compound has a molecular weight of 338.19 and formula C15H13Cl2N3O2. The SMILES notation is CCOC(=O)c1c(\C(=C/N)C#N)c2ccc(Cl)c(Cl)c2n1C. As a small molecule with moderate lipophilicity, it would be expected to have reasonable cell permeability and oral bioavailability. Comprehensive pharmacokinetic studies would be required for therapeutic development.
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| Toxicity/Toxicokinetics |
No detailed toxicology data is publicly available for KH-CB19. As a research compound, standard preclinical toxicology would be required for therapeutic development. The compound's excellent selectivity over Clk3 and against 71-kinases suggests a favorable specificity profile that may contribute to a manageable safety profile. However, potential effects on other kinases or off-target proteins would need to be assessed. The compound is for research use only.
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| References | |
| Additional Infomation |
KH-CB19 has the molecular formula C15H13Cl2N3O2 and molecular weight 338.19. The SMILES notation is CCOC(=O)c1c(\C(=C/N)C#N)c2ccc(Cl)c(Cl)c2n1C. It is an N-methylindolyl-enaminonitrile compound and a potent CLK inhibitor with CLK1 IC50 of 19.7 nM and CLK3 IC50 of 530 nM. It shows antiviral activity and inhibits influenza virus replication with an IC50 of 13.6 µM. No clinical trial status has been identified; it remains a research tool for studying CLK biology, cancer, and viral infections.
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| Molecular Formula |
C15H13CL2N3O2
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|---|---|
| Molecular Weight |
338.19
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| Exact Mass |
337.038
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| CAS # |
1354037-26-5
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| Related CAS # |
KH-CB20;1354448-60-4
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| PubChem CID |
44237094
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| Appearance |
White to light yellow solid powder
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| LogP |
4.185
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
22
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| Complexity |
516
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC(=O)C1=C(C2=C(N1C)C(=C(C=C2)Cl)Cl)/C(=C\N)/C#N
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| InChi Key |
CXJCGSPAPOTTSF-VURMDHGXSA-N
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| InChi Code |
InChI=1S/C15H13Cl2N3O2/c1-3-22-15(21)14-11(8(6-18)7-19)9-4-5-10(16)12(17)13(9)20(14)2/h4-6H,3,18H2,1-2H3/b8-6-
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| Chemical Name |
ethyl 3-[(E)-2-amino-1-cyanoethenyl]-6,7-dichloro-1-methylindole-2-carboxylate
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| Synonyms |
KHCB19; KH CB19; KH-CB19
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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 : ≥ 50 mg/mL (~147.85 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.39 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 | 2.9569 mL | 14.7846 mL | 29.5692 mL | |
| 5 mM | 0.5914 mL | 2.9569 mL | 5.9138 mL | |
| 10 mM | 0.2957 mL | 1.4785 mL | 2.9569 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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