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| 100mg | ||
| 250mg | ||
| 500mg | ||
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| ln Vitro |
CDK8-IN-11(compound 29, 200 nM) hydrochloride exhibits 73.6% inhibitory activity against CDK8 [1]. The CDK8-IN-11 hydrochloride (0-50 μM, 48 h) suppresses the growth of HCT-116, HHT-29, SW480, CT-26, and GES-1 cells [1]. In HCT-116 cells, CDK8-mediated phosphorylation of STAT1 at Ser727 is inhibited by CDK8-IN-11(0-4 μM, 48 h) hydrochloride[1]. In HCT-116 cells, CDK8-IN-11 hydrochloride (0–4 μM, 24 h) inhibits conventional WNT/β-catenin signaling pathways and deregulates β-catenin-mediated transcription[1]. In HCT-116 cells, CDK8-IN-11(0.5-2 μM, 48 h) hydrochloride enhances the number of G1 phase cells[1]. Hydrochloride CDK8-IN-11(0–4 μM) reverses HCT-116 cells' resistance to sorafenib[1].
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| ln Vivo |
In CT-26 xenograft mice, CDK8-IN-11 (compound 29, 10 and 40 mg/kg, po) hydrochloride suppresses the formation of tumors[1]. Within seven days, CDK8-IN-11 hydrochloride (1000 mg/kg, oral gavage, ICR mice) exhibits no overt aberrant behavior[1]. Rats treated with 10 mg/kg po or 2 mg/kg iv with CDK8-IN-11 hydrochloride exhibit considerable permeability, as measured by an apparent permeability coefficient of 1.8 × 10−6 cm/s[1].
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: HCT-116, HHT-29, SW480, CT-26, GES-1 cells Tested Concentrations: 0.08, 0.4, 2, 10, and 50 μM Incubation Duration: 48 h Experimental Results: Inhibited cell proliferation with IC50 values of 1.2, 0.7, 2.4, 5.5, 62.7 nM respectively. Western Blot Analysis[1] Cell Types: HCT-116 cell Tested Concentrations: 0, 1, 2, 4 μM Incubation Duration: 48 h Experimental Results: Inhibited the phosphorylation of STAT1 at Ser727 without affecting the JAK-regulated phosphorylation at Tyr701. Cell Cycle Analysis[1] Cell Types: HCT-116 cell Tested Concentrations: 0.5-2 μM Incubation Duration: 48 h Experimental Results: Increased the number of cells in the G1 phase with an obvious diminished percentage of cells in the G2/M and S phase in HCT-116 cells. |
| Animal Protocol |
Animal/Disease Models: CT-26 xenograft mice[1]
Doses: 10 and 40 mg/kg Route of Administration: Oral adminstration (po) Experimental Results: decreased the tumor volume, decreased β-catenin and c-Myc level in tumor. Animal/Disease Models: decreased the tumor volume, decreased β-catenin and c-Myc level in tumor. Doses: 10 mg/kg (po), 2 mg/kg (iv) Route of Administration: Oral adminstration (po) or intravenous (iv) injection ( iv) Experimental Results: pharmacokinetic/PK profile of CDK8-IN-11 (compound 29). dose (mg/kg) T1/2 (h) Tmax (h) Cmax (ng/mL) F (%) 10 (po) 1.1 0.8 453 31.7 2 (iv) 0.5 318 |
| References |
[1]. Yao Yao Yan, et al. Design and Synthesis of a 2-Amino-pyridine Derivative as a Potent CDK8 Inhibitor for Anti-colorectal Cancer Therapy. J Med Chem. 2022 Sep 20.
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| Molecular Formula |
C19H16CLF3N4O2
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|---|---|
| Molecular Weight |
424.80
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| Related CAS # |
CDK8-IN-11;2839338-28-0
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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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3540 mL | 11.7702 mL | 23.5405 mL | |
| 5 mM | 0.4708 mL | 2.3540 mL | 4.7081 mL | |
| 10 mM | 0.2354 mL | 1.1770 mL | 2.3540 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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