| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Senexin B selectively targets CDK8 and CDK19. It exhibits Kd values of 140 nM for CDK8 and 80 nM for CDK19. Its IC50 values range from 24 to 50 nM. By inhibiting these kinases, it modulates transcriptional regulation and shows anti-cancer activity.
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|---|---|
| ln Vitro |
In vitro, Senexin B is a potent inhibitor of CDK8/19 with IC50 values ranging from 24 to 50 nM. It exhibits Kd values of 140 nM for CDK8 and 80 nM for CDK19. It inhibits cell growth in estrogen-containing media in breast cancer cells (MCF-7, BT474, and T47D-ER/Luc) in a concentration-dependent manner (1.25-5 μM). It strongly reduces the emergence of estrogen-independent cells.
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| ln Vivo |
In vivo, Senexin B significantly slows tumor growth and inhibits tumor progression in triple-negative breast cancer (TNBC) xenograft models. Its oral bioavailability makes it suitable for in vivo studies.
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| Enzyme Assay |
In vitro enzyme assays for Senexin B involve measuring the inhibition of purified CDK8 and CDK19 kinase activity. The enzymes are incubated with a peptide substrate and ATP in the presence of varying concentrations of the compound. The phosphorylation of the substrate is measured using radioactivity or fluorescence-based methods to determine the IC50 or Kd.
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| Cell Assay |
In vitro cellular assays for Senexin B are performed using breast cancer cell lines, such as MCF-7, BT474, and T47D-ER/Luc. Cells are treated with the compound for several days, and cell viability is measured using CellTiter-Glo or MTT assays. The compound's effect on cell cycle progression and apoptosis is also assessed.
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| Animal Protocol |
In vivo animal studies for Senexin B are conducted in mouse xenograft models using triple-negative breast cancer (TNBC) cell lines. Tumor-bearing mice are treated with the compound orally, and tumor growth is measured. The compound's ability to inhibit tumor growth and its effects on CDK8/19 signaling in tumor tissue are assessed.
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| ADME/Pharmacokinetics |
Senexin B is an orally available compound. Its PK properties have been characterized in preclinical species, supporting its use in in vivo efficacy studies. Its oral bioavailability allows for convenient dosing in animal models.
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| Toxicity/Toxicokinetics |
Toxicological data for Senexin B are not detailed in publicly available sources. As an anti-cancer agent in development, its safety profile would be evaluated in standard toxicology studies.
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| References |
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| Additional Infomation |
BCD 115, a cyclin-dependent kinase 8/19 inhibitor, is an orally bioavailable inhibitor of cyclin-dependent kinases 8 and 19 (CDK8/19) with potential antitumor and chemoprotective activities. After oral administration, BCD 115 binds to CDK8/19 and inhibits its activity, thereby preventing the activation of CDK8/19-mediated oncogenic signaling pathways, blocking the selective transcription of certain pro-tumorigenic genes, and inhibiting the proliferation of CDK8/19-overexpressing tumor cells. CDKs are serine/threonine kinases involved in cell cycle regulation and may be overexpressed in some cancer cell types. CDK8 plays a crucial role in transcriptional regulation and is an important oncogenic driver in various cancer cell types.
Senexin B is also known as SNX2-1-165 and BCD-115. It is a potent and selective CDK8/19 inhibitor. It is being developed for the treatment of cancer. It is not an approved drug. |
| Molecular Formula |
C27H26N6O
|
|---|---|
| Molecular Weight |
450.535
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| Exact Mass |
450.216
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| CAS # |
1449228-40-3
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| PubChem CID |
71661259
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| Appearance |
White to off-white solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
743
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1CCN(C(=O)C2C=C3C=CC(CC/N=C4\NC=NC5=CC=C(C#N)C=C\45)=CC3=CC=2)CC1
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| InChi Key |
VNADJTWHOAMTLY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H26N6O/c1-32-10-12-33(13-11-32)27(34)23-6-5-21-14-19(2-4-22(21)16-23)8-9-29-26-24-15-20(17-28)3-7-25(24)30-18-31-26/h2-7,14-16,18H,8-13H2,1H3,(H,29,30,31)
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| Chemical Name |
4-[2-[6-(4-methylpiperazine-1-carbonyl)naphthalen-2-yl]ethylamino]quinazoline-6-carbonitrile
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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) |
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
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2196 mL | 11.0978 mL | 22.1956 mL | |
| 5 mM | 0.4439 mL | 2.2196 mL | 4.4391 mL | |
| 10 mM | 0.2220 mL | 1.1098 mL | 2.2196 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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