Physicochemical Properties
| Molecular Formula | C19H16CLF3N4O2 |
| Molecular Weight | 424.80 |
| Related CAS # | CDK8-IN-11;2839338-28-0 |
| Appearance | Typically exists as solid at room temperature |
| 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) |
Biological Activity
| 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]. |
| 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]. |
| 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]. 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. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |