Senexin A

Catalog No.S8520 Batch:S852001

Technical Data

Formula	C₁₇H₁₄N₄
Molecular Weight	274.32	CAS No.	1366002-50-7
Solubility (25°C)*	In vitro	DMSO	54 mg/mL (196.85 mM)
		Ethanol	54 mg/mL (196.85 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

Senexin A is a potent and selective inhibitor of CDK8 and its nearest relative, CDK19 with Kd values of 0.83 μM and 0.31 μM for CDK8 and CDK19 ATP site binding, respectively.

Targets

CDK19 ^[1] (Cell-free assay)	CDK8 ^[1] (Cell-free assay)
0.31 μM(Kd)	0.83 μM(Kd)

In vitro

p21 is shown to activate NF-κB–dependent transcription, and Senexin A inhibits p21-stimulated activity of the consensus NF-κB–dependent promoter. Senexin A has no effect on p21 induction by IPTG, on cell growth with or without p21, or on p21-induced senescent phenotype. Senexin A does not affect the inhibition of gene expression by p21 and does not interfere with p21-mediated inhibition of large sets of genes belonging to Gene Ontology (GO) categories of mitosis and DNA replication. Senexin A inhibits only p21-induced transcription but not other biological effects of p21. Senexin A inhibits CDK8 and CDK19 ATP site binding with Kd50 of 0.83 μM and 0.31 μM, respectively and CDK8 kinase activity with IC50 of 0.28 μM. Senexin A inhibits β-catenin–dependent transcription in HCT116 colon carcinoma cells. It does not inhibit ROCK and did not share cortistatin A's strong antiendothelial cell activity^[1].

In vivo

The CDK8/19 inhibitor Senexin A reverses chemotherapy-induced paracrine tumor-promoting activities in vivo and does not inhibit reporter cell growth and showed no detectable toxicity in a mouse study^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines MEF Concentrations 1 μM Incubation Time 24 h Method For conditioned media mitogenic assays, MEF, untreated or treated for 24 h with 200 nM doxorubicin, alone or in combination with 1 μM Senexin A, were washed and cultured for 48 h without drugs to collect conditioned media. The media were added to A549 cells, plated on 12-well plates at 10⁴ cells per well; cells were counted after 48 h using the trypan blue exclusion assay. Experiments were performed in triplicate, and cells counted in at least three optical fields per experiment.
Animal Study:^{^[1]}	Animal Models C57BL/6 mice Dosages 20 mg/kg Administration i.p.

Cell Assay:^{^[1]}

Cell lines
MEF
Concentrations
1 μM
Incubation Time
24 h
Method
For conditioned media mitogenic assays, MEF, untreated or treated for 24 h with 200 nM doxorubicin, alone or in combination with 1 μM Senexin A, were washed and cultured for 48 h without drugs to collect conditioned media. The media were added to A549 cells, plated on 12-well plates at 10⁴ cells per well; cells were counted after 48 h using the trypan blue exclusion assay. Experiments were performed in triplicate, and cells counted in at least three optical fields per experiment.

Animal Study:^{^[1]}

Animal Models
C57BL/6 mice
Dosages
20 mg/kg
Administration
i.p.

References

[1] Porter DC, et al. Proc Natl Acad Sci U S A. 2012, 109(34):13799-804.

Selleck's Senexin A has been cited by 2 publications

P-TEFb promotes cell survival upon p53 activation by suppressing intrinsic apoptosis pathway [ Nucleic Acids Res, 2023, gkad001]	PubMed: 36727434
Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer [ Breast Cancer Res, 2022, 24(1):41]	PubMed: 35715861

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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