Physicochemical Properties
| CAS # | 2850253-95-9 |
| 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 | Compound 22 (CDK8-IN-9) (0-100 μM, 48 h) has the ability to dramatically decrease TCF/LEF transcriptional activity mediated by β-catenin and inhibit cell proliferation by targeting CDK8 to prevent the activation of the WNT/β-catenin pathway[1]. Rather than causing apoptosis, CDK8-IN-9 (compound 22) (0.5, 1 and 2 μM, 24 h) inhibits cell growth by inducing G2/M and S-phase cell cycle arrest[1]. |
| ln Vivo | At a dose of 80 mg/kg, CDK8-IN-9 (compound 22) dramatically lowers tumor volume and prevents mice from losing weight when they are infected with CT-26 murine colon cancer cells in Balb/c mice[1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: HCT-116, HT-29, SW-480, CT-26 and GES-1 cells Tested Concentrations: 0-100 μM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibited HCT-116, HT-29 , SW-480, CT-26 and GES-1 cells with the GI50 values of 4.9, 4.3, 2.1, 4.0 and 61.5 μM, respectively. Cell Cycle Analysis[1] Cell Types: HCT-116 cells Tested Concentrations: 0.5, 1, and 2 μM Incubation Duration: 24 hrs (hours) Experimental Results: Arrested cells in G2/M phase by 17%, 20.26% and 34.45% at concentrations of 0.5, 1, and 2 μM, respectively. demonstrated a decrease in the G0/G1 phase and a slight increase in the S phase. |
| Animal Protocol |
Animal/Disease Models: Sprague−Dawley rats[1] Doses: 10 mg/kg or 5 mg/kg Route of Administration: po for 10 mg/kg and iv for 5 mg/kg Experimental Results: The pharmacokinetic/PK parameters of CDK8-IN-9 (compound 22) Parameters t1/2 (h) Tmax (h) MRT (h) Cmax (μg/L) AUC0-∞ (μg/L·h) CL (L/h /kg) F (%) 10 mg/kg (po) 1.21 0.75 2.022 497.56 783.66 9.23 39.8 5 mg/kg (iv) 1.63 - 1.756 706.29 983.09 11.32 - |
| References |
[1]. Discovery of the Novel 1H-Pyrrolo[2,3-b]pyridine Derivative as a Potent Type II CDK8 Inhibitor against Colorectal Cancer. J. Med. Chem. |
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.) |