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1 mg

Ref. SYN-1081-M001

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Neuf 112.00 H.T.


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Détails Produit

Product description: Chemical. CAS: 1057249-41-8. Formula: C18H15ClN6OS2. MW: 430.9. Aurora kinases constitute a family of serine-threonine kinases that are strongly associated with cancer. Aurora A and B are essential in mitosis. Perturbation of their activity leads to multiple defects in mitosis including aberrant centrosome duplication, misalignment of chromosomes, inhibition of cytokinesis, and disruption of the spindle checkpoint. The role of Aurora C is unclear; however, Aurora C can complement Aurora B kinase activity in mitosis. SNS-314 is an ATP-competitive, selective, and potent nanomolar inhibitor of aurora kinases in vitro. A cocrystal structure of SNS-314 with Aurora A confirms that SNS-314 engages the purine-binding pocket of Aurora. SNS-314 inhibits cellular proliferation in the HCT116 colorectal carcinoma cell line with an EC50 of ~5nM. Analysis of DNA content and indirect immunofluoresence demonstrates that SNS-314 induces defects in cytokinesis and spindle checkpoint that are consistent with Aurora kinase inhibition. Phosphorylation of Histone H3 on serine 10, a known Aurora B cellular target, is inhibited with an EC50 of ~9nM following treatment of cells with SNS-314. Administration of SNS-314 to HCT116 tumor bearing mice potently suppresses tumor growth. Analysis of SNS-314 treated tumors confirms that the anti-tumor activity is consistent with Aurora kinase inhibition. SNS-314 is a potent small-molecule inhibitor of Aurora kinase that is being developed as a novel anti-cancer therapeutic agent.

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