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| 25mg |
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| 50mg |
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| Targets |
CDK8 51.9 nM (IC50)
CDK8-IN-13 targets CDK8, a cyclin-dependent kinase that is part of the Mediator complex and regulates transcription. The compound inhibits CDK8 with an IC50 of 51.9 nM. By inhibiting CDK8, the compound decreases the expression of p-STAT1 S727 and p-STAT5 S726, which are downstream targets of CDK8-mediated phosphorylation. The compound induces apoptosis and shows antitumor activity. |
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| ln Vitro |
In HCT-116 cells, CDK8-IN-13 (compound 43; 1, 2.5, 5, 10 µM; 12 h) dose-dependently decreases the expression of p-STAT1 S727 and p-STAT5 S726[1]. Apoptosis is induced by CDK8-IN -13 (0, 1, 5, 10 µM; 48 h) in a dose-dependent manner [1].
In vitro studies demonstrate that CDK8-IN-13 induces apoptosis and decreases the expression of p-STAT1 S727 and p-STAT5 S726. The compound inhibits CDK8 with an IC50 of 51.9 nM. It shows antitumor activity. CDK8-IN-13 has been widely used as a lead compound for analyzing binding modes with the CDK8 active site in molecular docking experiments. The compound is potent, selective, and orally active. |
| ln Vivo |
In mice, CDK8-IN-13 (40, 80 mg/kg; oral; for 15 days) dose-dependently suppresses the growth of tumors [1].
In vivo, CDK8-IN-13 shows antitumor activity. The compound is orally active, indicating favorable oral bioavailability. It induces apoptosis and decreases the expression of p-STAT1 S727 and p-STAT5 S726. The compound has been used as a lead compound for drug development. Further studies would be needed to fully evaluate its efficacy in various cancer models. |
| Enzyme Assay |
The CDK8 inhibitory activity of CDK8-IN-13 can be assessed using in vitro kinase assays. In a typical assay, recombinant CDK8 kinase is incubated with a peptide substrate, ATP (including radiolabeled ³³P-ATP), and varying concentrations of CDK8-IN-13. The incorporation of phosphate into the substrate is measured, and the IC50 is calculated. The IC50 for CDK8 inhibition is 51.9 nM. Molecular docking experiments can be used to analyze binding modes with the CDK8 active site.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: molm-13, HL-60, MV4-11, MGC-803, MDA-MB-231, A375, A549 cells Tested Concentrations: 0-50 µM Incubation Duration: Experimental Results: demonstrated antiproliferative activity with GC50s of 1.57, 1.00, 4.61, >50, >50, >50, >50 µM, respectively. Western Blot Analysis[1] Cell Types: HCT-116 cells Tested Concentrations: 1, 2.5, 5, 10 µM Incubation Duration: 12 h Experimental Results: diminished the expression of p-STAT1 S727 and p-STAT5 S726, and suppressed the phosphorylation of STAT1 S727 induced by IFN-γ (10 ng/mL) in a dose-dependent manner. Apoptosis Analysis[1] Cell Types: HL-60 cells Tested Concentrations: 0, 1, 5, 10 µM Incubation Duration: 48 h Experimental Results: Induced approximately 7% and 36% apoptotic at concentrations of 5 and 10 μM, respectively. The cellular activity of CDK8-IN-13 is assessed using cancer cell lines. Cells are treated with escalating concentrations of CDK8-IN-13. Cell viability is measured using MTT or CellTiter-Glo assays. Apoptosis is assessed by annexin V/propidium iodide staining or caspase activation assays. p-STAT1 S727 and p-STAT5 S726 expression is assessed by Western blotting using phospho-specific antibodies. Antitumor activity is assessed in appropriate cancer models. |
| Animal Protocol |
Animal/Disease Models: 6weeks old balb/c (Bagg ALBino) mouse: (C1498 cells)[1]
Doses: 40, 80 mg/kg Route of Administration: Po; for 15 days Experimental Results: diminished the tumor growth with no significant weight loss, the expression of Ki67 diminished in a dose-dependent manner, the level of phosphorylation of STAT1 S727 in tumor tissues was downregulated. CDK8-IN-13 has been evaluated in animal models of cancer. In these studies, the compound is administered orally. Tumor volumes are measured. The compound shows antitumor activity. It induces apoptosis and decreases the expression of p-STAT1 S727 and p-STAT5 S726. The compound has been used as a lead compound for drug development. |
| ADME/Pharmacokinetics |
CDK8-IN-13 is orally active, indicating favorable oral bioavailability. The compound has a molecular weight of 237.26 g/mol and a molecular formula of C14H11N3O. It is soluble in DMSO. Further studies would be needed to fully characterize its absorption, distribution, metabolism, and excretion properties, including half-life, Cmax, AUC, and tissue distribution.
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| Toxicity/Toxicokinetics |
No detailed toxicity data has been published for CDK8-IN-13. As a CDK8 inhibitor, it may have on-target effects on transcription in normal cells. Comprehensive toxicology studies would be required to evaluate its safety profile for potential therapeutic development. The compound is intended for research use only.
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| References | |
| Additional Infomation |
CDK8-IN-13 (CAS# 918523-75-8) is a potent, selective, and orally active CDK8 inhibitor with an IC50 of 51.9 nM. The compound induces apoptosis and decreases p-STAT1 S727 and p-STAT5 S726 expression. It shows antitumor activity. CDK8-IN-13 has been widely used as a lead compound for molecular docking studies with the CDK8 active site. The molecular formula is C14H11N3O and molecular weight is 237.26 g/mol.
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| Molecular Formula |
C14H11N3O
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| Exact Mass |
237.09
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| CAS # |
918523-75-8
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| PubChem CID |
58087073
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| Appearance |
White to off-white solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
18
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| Complexity |
320
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC(=C1)C(=O)N)C2=CN=C3C(=C2)C=CN3
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| InChi Key |
PQAJMNITAQGSCS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H11N3O/c15-13(18)10-3-1-2-9(6-10)12-7-11-4-5-16-14(11)17-8-12/h1-8H,(H2,15,18)(H,16,17)
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| Chemical Name |
3-(1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide
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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 : 125 mg/mL (526.85 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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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