| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
DB18 targets CDC2-like kinases (CLKs), a family of serine/threonine kinases that play critical roles in the regulation of RNA splicing. The CLK family includes CLK1, CLK2, CLK3, and CLK4, which phosphorylate serine/arginine-rich (SR) proteins. SR proteins are essential splicing factors that regulate alternative splicing of pre-mRNA. By phosphorylating SR proteins, CLKs modulate their activity, localization, and interactions with other splicing factors, thereby controlling the generation of different mRNA isoforms from a single gene. DB18 is a selective inhibitor of CLK1, CLK2, and CLK4 with IC50 values in the range of 10-30 nM. By inhibiting these kinases, DB18 disrupts RNA splicing and gene expression, leading to anti-tumor activity.
|
|---|---|
| ln Vitro |
In vitro, DB18 is a potent and selective inhibitor of CDC2-like kinases CLK1, CLK2, and CLK4 with IC50 values in the range of 10-30 nM. The compound's activity can be measured in kinase assays using recombinant CLK enzymes and appropriate peptide substrates. DB18 has anti-tumor activity, which can be assessed in cell-based assays measuring cancer cell proliferation, survival, and apoptosis. By inhibiting CLKs, DB18 disrupts RNA splicing and alters the expression of genes involved in cancer cell growth and survival. However, specific quantitative data for cell-based activity beyond the IC50 values have not been extensively reported in the available literature.
|
| ln Vivo |
In vivo activity data for DB18 are not available in the current scientific literature. As a selective CLK inhibitor with anti-tumor activity in vitro, the compound would be expected to have antitumor activity in vivo. However, specific animal model studies, dosing regimens, and quantitative outcomes have not been reported. The compound's selectivity for CLK1, CLK2, and CLK4 suggests that it may have potential for in vivo applications in cancer research. Further in vivo studies would be required to characterize its efficacy, safety, and pharmacokinetic properties in animal models of cancer.
|
| Enzyme Assay |
In vitro enzyme assay protocols for DB18 would typically involve measuring its inhibition of CLK1, CLK2, and CLK4 kinase activities. A standard protocol would involve incubating recombinant CLK enzymes with varying concentrations of DB18 (typically 0.1 nM to 10 μM), ATP, and a peptide substrate (e.g., an SR protein-derived peptide or a generic kinase substrate) in kinase assay buffer at 30°C for a defined period. The extent of substrate phosphorylation is measured using methods such as 33P-ATP incorporation, TR-FRET, or luminescent kinase assays (e.g., ADP-Glo). IC50 values are determined from concentration-response curves for each CLK isoform. Selectivity profiling can be performed by testing the compound against a panel of kinases to assess its specificity.
|
| Cell Assay |
In vitro cell-based assay protocols for DB18 would typically involve assessing its effects on cancer cell proliferation, survival, and RNA splicing. A standard protocol would involve seeding cancer cell lines in multi-well plates and treating them with varying concentrations of DB18 (typically 0.1 nM to 10 μM) for 24-72 hours. Cell proliferation is assessed using MTT, CellTiter-Glo, or colony formation assays. RNA splicing can be assessed by RT-PCR or RNA-seq to analyze changes in alternative splicing patterns. Apoptosis can be assessed by Annexin V staining or caspase activity assays. Appropriate controls include vehicle-treated cells and cells treated with a known CLK inhibitor for comparison.
|
| Animal Protocol |
In vivo animal experimental protocols for DB18 have not been reported in the available literature. Based on its in vitro anti-tumor activity, potential studies might involve using mouse xenograft models of cancer. A hypothetical protocol would involve implanting cancer cells subcutaneously in immunodeficient mice, allowing tumors to reach a certain size, and then administering DB18 via oral gavage or intraperitoneal injection at doses determined from preliminary pharmacokinetic and tolerability studies. Treatment would typically be administered daily for 2-4 weeks. Endpoints would include tumor volume measurement, tumor weight at necropsy, assessment of CLK inhibition and RNA splicing changes in tumor tissues, and evaluation of apoptosis.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of DB18 have not been characterized in published studies. The compound has a molecular weight of 487.90 and a molecular formula of C24H18ClN7O3. Specific PK parameters such as half-life, Cmax, AUC, bioavailability, volume of distribution, and clearance have not been reported. The compound's metabolism, protein binding, and routes of elimination remain to be characterized. Further pharmacokinetic studies would be required to understand its absorption, distribution, metabolism, and excretion profile. The compound is intended for research use only and is not intended for human use.
|
| References | |
| Additional Infomation |
DB18 is a research-grade compound that functions as a potent and selective inhibitor of CDC2-like kinases (CLKs), with IC50 values in the range of 10-30 nM for CLK1, CLK2, and CLK4. The compound has anti-tumor activity and is used in cancer research to study the role of CLK kinases in RNA splicing and gene expression. It has not entered clinical trials and is not approved for any therapeutic indication. Its mechanism of action involves inhibition of CLK kinases, disrupting RNA splicing and gene expression. The compound is available exclusively for research purposes and is not intended for diagnostic, therapeutic, or human applications.
|
| Molecular Formula |
C24H18CLN7O3
|
|---|---|
| Molecular Weight |
487.897822856903
|
| CAS # |
2587177-94-2
|
| Appearance |
Light yellow to yellow solid powder
|
| SMILES |
ClC1=CC=CC(=C1)NC1=NC=C2C=CC=C(C2=N1)OCC1=CN(C2C=CC(C)=CC=2[N+](=O)[O-])N=N1
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO :~50 mg/mL (~102.48 mM; with sonication (<60°C))
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.12 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one),clear solution; with ultrasonication.
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 and add it to 400 μL PEG300 and mix well. Then add 50 μL Tween-80 to the above system and mix well. Then continue to add 450 μL of physiological saline to make up 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 (5.12 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one),clear solution; with ultrasonication. 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 and add it to 900 μL corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0496 mL | 10.2480 mL | 20.4960 mL | |
| 5 mM | 0.4099 mL | 2.0496 mL | 4.0992 mL | |
| 10 mM | 0.2050 mL | 1.0248 mL | 2.0496 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
