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    Senexin A
    Senexin A

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V2743
    CAS #: 1366002-50-7Purity ≥98%

    Description: Senexin A is a novel, potent, selective and ATP site competitive inhibitor of CDK8 and CDK19 with Kd values of 0.83 μM and 0.31 μM for CDK8 and CDK19, respectively. Conventional chemotherapy not only kills tumor cells but also changes gene expression in treatment-damaged tissues, inducing production of multiple tumor-supporting secreted factors. This secretory phenotype was found to be mediated in part by a damage-inducible cell-cycle inhibitor p21 (CDKN1A). Senexin A inhibits damage-induced transcription downstream of p21. Senexin A suppresses damage-induced tumor-promoting paracrine activities of tumor cells and normal fibroblasts and reverses the increase in tumor engraftment and serum mitogenic activity in mice pretreated with a chemotherapeutic drug. Senexin A also increases the efficacy of chemotherapy against xenografts formed by tumor cell/fibroblast mixtures. Microarray data analysis revealed striking correlations between CDK8 expression and poor survival in breast and ovarian cancers. CDK8 inhibition by Senexin A offers a promising approach to increasing the efficacy of cancer chemotherapy.

    References:  2012 Aug 21;109(34):13799-804. 


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    Molecular Weight (MW) 274.32
    Formula C17H14N4
    CAS No. 1366002-50-7
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: >50 mg/mL
    Water: < 1mg/mL
    Ethanol: >50 mg/mL
    Chemical Name 4-[(2-Phenylethyl)amino]-6-quinazolinecarbonitril
    Synonyms Senexin A
    SMILES Code N#CC1=CC2=C(NCCC3=CC=CC=C3)N=CN=C2C=C1


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    In Vitro

    In vitro activity:  Senexin A is a novel, potent, selective and ATP site competitive inhibitor of CDK8 and CDK19 with Kd values of 0.83 μM and 0.31 μM for CDK8 and CDK19, respectively. Conventional chemotherapy not only kills tumor cells but also changes gene expression in treatment-damaged tissues, inducing production of multiple tumor-supporting secreted factors. This secretory phenotype was found to be mediated in part by a damage-inducible cell-cycle inhibitor p21 (CDKN1A). Senexin A inhibits damage-induced transcription downstream of p21. Senexin A suppresses damage-induced tumor-promoting paracrine activities of tumor cells and normal fibroblasts and reverses the increase in tumor engraftment and serum mitogenic activity in mice pretreated with a chemotherapeutic drug. Senexin A also increases the efficacy of chemotherapy against xenografts formed by tumor cell/fibroblast mixtures. Microarray data analysis revealed striking correlations between CDK8 expression and poor survival in breast and ovarian cancers. CDK8 inhibition by Senexin A offers a promising approach to increasing the efficacy of cancer chemotherapy.


    Kinase Assay: 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 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. 


    Cell Assay: 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.

    In VivoSenexin A shows no detectable toxicity and no significant effects on body weight, organ weights, or blood cell counts in C57BL/6 mice during the treatment. This effect of doxorubicin treatment is completely abolished, however, when doxorubicin injection is followed by administration of Senexin A. Senexin A treatment strongly improves the response of A549/MEF tumors to doxorubicin[
    Animal model C57BL/6 mice
    Formulation & Dosage Dissolved in 80% propylene glycol; 20 mg/kg; i.p. injection
    References  2012 Aug 21;109(34):13799-804. 


    These protocols are for reference only. InvivoChem does not independently validate these methods.

    Senexin A


    Effects of Senexin A on the induction of transcription by IPTG-inducible p21.

     Senexin A


    Identification of CDK8 as a mediator of p21-induced transcription and target of SNX2-class compounds.

     Senexin A


    Effects of p21 and CDK8 inhibitor on paracrine tumor-promoting activities.

     Senexin A


    Effects of CDK8 inhibitor and clinical correlations of CDK8 expression in vivo.




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