Physicochemical Properties
| Molecular Formula | C19H20N4O3 |
| Molecular Weight | 352.39 |
| CAS # | 2988020-03-5 |
| Appearance | Typically exists as solids 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
| Targets | CDK8 57 nM (IC50) |
| ln Vitro | CDK8-IN-15 has the highest anti-CDK8 activity, with an IC50 value of 57.3 nM, and has a positive effect on TNF-α-induced psoriasis in the HaCat cell model, with an IC50 value of 4.6 μM [1]. CDK8-IN-15 (5 μM, 4 h) inhibits CDK8 enzymatic activity and enhances the thermal stability of endogenous and exogenous CDK8 in HEK293T-CDK8 cells [1]. CDK8-IN-15 (0,1,2,4 μM, 75h) significantly reduces the levels of CXCL1, CXCL2, and IL-8 after treating HEK293 cells [1]. |
| ln Vivo | CDK8-IN-15 (2 MG/KG, iv and 10 mg/kg, po) has high Caco-2 permeability in rats and has no significant inhibitory effect on the five cytochrome p450 isozymes [1]. CDK8-IN-15 does not cause significant tissue damage in ICE mice [1]. CDK8-IN-15 (5/10/20 MG/KG, po) may enhance IL-10 production and Foxp3 expression in IMQ-induced psoriasis model mice by targeting CDK8, thereby alleviating psoriasis [1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: HaCat Tested Concentrations: 0, 1 μM, 2 μM, 4 μM Incubation Duration: 75 h Experimental Results: Down-regulated the levels of IL-8 and IL-6 in a dose-dependent manner with values of 0, 1 μM, 2 μM, 4 μM . Western Blot Analysis[1] Cell Types: HEK293T-CDK8 Tested Concentrations: 5 μM Incubation Duration: 4 h Experimental Results: Enhanced the thermal stability of endogenous and exogenous CDK8. Western Blot Analysis[1] Cell Types: HEK 293 Tested Concentrations: 1 μM Incubation Duration: 0, 1, 2, 4, 8, 12 h. Experimental Results: Had a great NF-κB transcriptional activity inhibitory effect with an IC50 value of 1 μM. |
| Animal Protocol |
Animal/Disease Models: Rats[1] Doses: 2 mg/kg, iv and 10 mg/kg, po Route of Administration: iv and po, a single administration Experimental Results: Showed high Caco-2 permeability in rats Animal/Disease Models: Imiquimod-induced psoriasis model of mice[1] Doses: 5, 10, 20 mg/kg Route of Administration: 5 % imiquimod cream and 5, 10, 20 mg/kg daily, p.o. Experimental Results: Alleviated the symptoms of imiquimod-induced psoriasis and increase the productions of TNF-α and IL-6 in imiquimod-induced psoriasis model of mice Animal/Disease Models: ICR mice[1]. Doses: 1000 mg/kg Route of Administration: i.g., a single administration Experimental Results: Didn’t cause a significant tissue damage on ICR mice |
| References |
[1]. Yan YY, et al.The discovery of a novel pyrrolo[2,3-b]pyridine as a selective CDK8 inhibitor offers a new approach against psoriasis[J]. 2024 May 6;175, 0753-3322. |
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 | 2.8378 mL | 14.1888 mL | 28.3776 mL | |
| 5 mM | 0.5676 mL | 2.8378 mL | 5.6755 mL | |
| 10 mM | 0.2838 mL | 1.4189 mL | 2.8378 mL |