Senexin B (Synonyms: SNX2-1-165) |
| Catalog No.GC19326 |
Senexin B is a potent, highly water-soluble and bioavailable CDK8/19 inhibitor, with Kds of 140 nM for CDK8 and 80 nM for CDK19.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1449228-40-3
Sample solution is provided at 25 µL, 10mM.
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Senexin B is a potent, highly water-soluble and bioavailable CDK8/19 inhibitor, with Kds of 140 nM for CDK8 and 80 nM for CDK19.
Senexin B inhibits CDK8/19 in low nanomolar range[1]. Senexin B is a newly optimized derivative of Senexin A. It has the same high selectivity for CDK8/19 and is more potent than Senexin A. Senexin B strongly reduces the emergence of estrogen independent cells. Senexin B shows synergy with fulvestrant in MCF7, T47D-ER/Luc and BT474[2].
Pretreatment of tumor-free mice with Senexin B significantly inhibits the growth of triple-negative breast cancer (TNBC) cells inoculated into mice subsequently to Senexin B administration, indicating a general chemopreventive effect on the normal tissue "soil". Senexin B potentiates the tumor-suppressive effect of doxorubicin on established TNBC xenografts; this effect is associated with the suppression of NFκB-mediated transcriptional induction of tumor-promoting cytokines. Senexin B inhibits invasive growth into the muscle layer in an orthotopic xenograft model of MDA-MB-468 TNBC cells. In a spleen-to-liver colon cancer metastasis model of syngeneic mouse CT26 tumors, Senexin B treatment of mice have the same effect as CDK8 knockdown in tumor cells: suppression of metastatic growth in the liver without a significant effect on primary tumor growth in the spleen[1]. Senexin B suppresses tumor growth and augmentes the effects of fulvestrant in ER-positive breast cancer xenografts[2].
References:
[1]. Porter D, et al. Abstract PR08: Targeting tumor microenvironment with selective small-molecule inhibitors of CDK8/19. Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr PR08. doi:10.1158/1538-7445.CHTME14-PR08
[2]. McDermott MS, et al. Inhibition of CDK8 mediator kinase suppresses estrogen dependent transcription and the growth of estrogen receptor positive breast cancer. Oncotarget. 2017 Feb 21;8(8):12558-12575.
[3]. CDK8-CDK19 selective inhibitors and their use in anti-metastatic and chemopreventative methods for cancer. US 9321737 B2
Animal experiment: | Mice: Once tumors reach 100-200 mm3 volume, 4 groups of mice are treated with vehicle, Senexin B dimaleate (100 mg/kg; twice daily, oral gavage in 6.25% 2-Hydroxypropyl-β-cyclodextrin, 1% Dextrose buffer) alone or in combination with fulvestrant (5 mg/mouse; s.c; once/week). Tumor volumes are measured twice weekly with calipers and volumes are calculated. After 40 days mice are euthanized, tumors are excised and weighed[2]. |
References: [1]. Porter D, et al. Abstract PR08: Targeting tumor microenvironment with selective small-molecule inhibitors of CDK8/19. Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr PR08. doi:10.1158/1538-7445.CHTME14-PR08 | |
| Cas No. | 1449228-40-3 | SDF | |
| Synonyms | SNX2-1-165 | ||
| Canonical SMILES | N#CC1=CC2=C(NCCC3=CC=C4C=C(C(N5CCN(C)CC5)=O)C=CC4=C3)N=CN=C2C=C1 | ||
| Formula | C27H26N6O | M.Wt | 450.53 |
| Solubility | DMSO : 6 mg/mL (13.32 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2196 mL | 11.098 mL | 22.1961 mL |
| 5 mM | 0.4439 mL | 2.2196 mL | 4.4392 mL |
| 10 mM | 0.222 mL | 1.1098 mL | 2.2196 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 19 reference(s) in Google Scholar.)
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