| Identification | Back Directory | [Name]
Senexin B | [CAS]
1449228-40-3 | [Synonyms]
Senexin B
SNX2-1-165
Senexin B (SNX2-1-165)
4-(2-(6-(4-methylpiperazine-1-carbonyl)naphthalen-2-yl)ethylamino)quinazoline-6-carbonitrile
6-Quinazolinecarbonitrile, 4-[[2-[6-[(4-methyl-1-piperazinyl)carbonyl]-2-naphthalenyl]ethyl]amino]- | [Molecular Formula]
C27H26N6O | [MDL Number]
MFCD31544331 | [MOL File]
1449228-40-3.mol | [Molecular Weight]
450.53 |
| Chemical Properties | Back Directory | [Boiling point ]
724.8±60.0 °C(Predicted) | [density ]
1.32±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
>22.6mg/mL in DMSO | [form ]
Powder | [pka]
6.74±0.10(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
Senexin B (SNX2-1-165; BCD-115) is a potent, highly water-soluble and bioavailable CDK8/19 inhibitor, with Kds of 140 nM for CDK8 and 80 nM for CDK19. | [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]. | [IC 50]
CDK19: 80 nM (Kd); CDK8: 140 nM (Kd) | [storage]
Store at -20°C | [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. DOI:10.18632/oncotarget.14894
[3] CDK8-CDK19 selective inhibitors and their use in anti-metastatic and chemopreventative methods for cancer. US 9321737 B2 |
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