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| 5mg |
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| 10mg |
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| Targets |
CDK8-IN-II targets cyclin-dependent kinase 8 (CDK8), a component of the mediator complex that regulates RNA polymerase II transcription. CDK8 is involved in the regulation of various signaling pathways, including Wnt/β-catenin, TGFβ, and Notch. Inhibition of CDK8 by CDK8-IN-II can modulate transcriptional programs involved in cancer and inflammation.
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| ln Vitro |
In vitro, CDK8-IN-II demonstrates potent inhibition of CDK8 with an IC50 of 0.2 nM. It shows high selectivity for CDK8 over other kinases. The compound effectively inhibits CDK8-mediated phosphorylation and transcriptional activity in cell-based assays. Detailed in vitro characterization including IC50 values and selectivity profile are available from published studies.
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| ln Vivo |
In vivo, CDK8-IN-II has been studied for its effects on CDK8-mediated transcriptional regulation in animal models of cancer and inflammatory diseases. As a potent CDK8 inhibitor, it may suppress tumor growth and modulate inflammatory responses. Specific in vivo data including dose-response relationships and efficacy in disease models are available from published studies.
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| Enzyme Assay |
In vitro kinase assays for CDK8 inhibition typically use recombinant CDK8 enzyme and a suitable substrate (e.g., a peptide or protein substrate). The enzyme is incubated with ATP and the substrate in the presence of varying concentrations of CDK8-IN-II. Kinase activity is measured by detecting phosphorylation of the substrate using radiometric (³²P-ATP) or luminescence-based methods. IC50 values are calculated from dose-response curves.
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| Cell Assay |
In vitro cellular assays for CDK8 inhibitors typically use cancer cell lines or cells expressing CDK8. Cells are treated with CDK8-IN-II at various concentrations, and CDK8-mediated phosphorylation of downstream targets is assessed by Western blotting. Cell proliferation is measured by MTT or CCK-8 assays. CDK8-dependent transcriptional activity is assessed using reporter gene assays or qRT-PCR.
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| Animal Protocol |
In vivo animal studies for CDK8 inhibitors typically use xenograft tumor models in immunocompromised mice or syngeneic models. Animals are administered CDK8-IN-II orally or intraperitoneally at various doses. Tumor growth is monitored by caliper measurement. CDK8 target engagement and pathway modulation are assessed in tumor tissue by Western blotting or qRT-PCR.
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| ADME/Pharmacokinetics |
CDK8-IN-II is a small-molecule kinase inhibitor with favorable physicochemical properties for oral administration. It has a molecular weight of 330.38 and a LogP of 2.9. The compound is soluble in DMSO and is expected to have good oral bioavailability. It is metabolized in the liver, and its metabolites are excreted via the kidneys and bile.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of CDK8-IN-II would typically include acute and repeated-dose toxicity in rodents, as well as genotoxicity and safety pharmacology assessments. As a kinase inhibitor, potential off-target effects on other kinases should be monitored. The compound is generally well-tolerated at therapeutic doses in preclinical models.
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| References | |
| Additional Infomation |
CDK8-IN-II (Cdk8-IN-4) is a potent inhibitor of CDK8 with an IC50 of 0.2 nM. It is disclosed in patent WO2014090692A1 as example compound 16. CDK8 is a transcriptional regulator implicated in various cancers and inflammatory diseases. The compound is available for research use only and is not approved for clinical use.
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| Molecular Formula |
C20H18N4O
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|---|---|
| Molecular Weight |
330.383123874664
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| Exact Mass |
330.148
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| CAS # |
1613638-82-6
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| PubChem CID |
75202254
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| Appearance |
White to light yellow solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
25
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| Complexity |
415
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| Defined Atom Stereocenter Count |
1
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| SMILES |
OC[C@@H](C1C=CC=CC=1)NC1C=NC=C(C=1)C1C=CC2=C(C=NN2)C=1
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| InChi Key |
VFKCKMKPKIUZOF-FQEVSTJZSA-N
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| InChi Code |
InChI=1S/C20H18N4O/c25-13-20(14-4-2-1-3-5-14)23-18-9-16(10-21-12-18)15-6-7-19-17(8-15)11-22-24-19/h1-12,20,23,25H,13H2,(H,22,24)/t20-/m0/s1
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| Chemical Name |
(2R)-2-[[5-(1H-indazol-5-yl)pyridin-3-yl]amino]-2-phenylethanol
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| Synonyms |
CDK8-IN-II CDK8 IN II CDK8INII
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ~100 mg/mL (~302.68 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.57 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 (7.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline 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 | 3.0268 mL | 15.1341 mL | 30.2682 mL | |
| 5 mM | 0.6054 mL | 3.0268 mL | 6.0536 mL | |
| 10 mM | 0.3027 mL | 1.5134 mL | 3.0268 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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