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| Cas No.: | 1449228-40-3 |
| Chemical Name: | 4-((2-(6-(4-Methylpiperazine-1-carbonyl)naphthalen-2-yl)ethyl)amino)quinazoline-6-carbonitrile |
| Synonyms: | SNX2-1-165 |
| SMILES: | O=C(N1CCN(C)CC1)C2=CC(C=CC(CCNC3=C(C=C(C#N)C=C4)C4=NC=N3)=C5)=C5C=C2 |
| Formula: | C27H26N6O |
| M.Wt: | 450.53 |
| Purity: | >98% |
| Sotrage: | 2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO |
| Description: | 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. |
| Target: | CDK19:80 nM (Kd) CDK8:140 nM (Kd) |
| In Vivo: | 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]. |
| In Vitro: | 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]. |
| Animal Administration: | 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 [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 |
MSDS
COA
| LOT NO. | DOWNLOAD |
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| 2018-0101 |
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| 2018-0101 |
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