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  • Title: Antitumor activity of NVP-AUY922, a novel heat shock protein 90 inhibitor, in human gastric cancer cells is mediated through proteasomal degradation of client proteins.
    Author: Lee KH, Lee JH, Han SW, Im SA, Kim TY, Oh DY, Bang YJ.
    Journal: Cancer Sci; 2011 Jul; 102(7):1388-95. PubMed ID: 21453385.
    Abstract:
    Heat shock protein 90 (HSP90) is a molecular chaperone required for the stability of key regulators of cell survival and is an emerging target of cancer therapy. NVP-AUY922, a novel and potent inhibitor of HSP90, was evaluated against gastric cancer cell lines. NVP-AUY922 significantly inhibited the proliferation of all tested gastric cancer cell lines with 50% inhibitory concentration in the range of 2-40 nM and potently induced the degradation of growth factor receptors and other client proteins including HER-2, Akt and thymidylate synthase. HSP70 was induced by NVP-AUY922 and its binding with client proteins led to their proteasomal degradation. Moreover, the combination of NVP-AUY922 with cytotoxic chemotherapeutic agents such as 5-fluorouracil and oxaliplatin created a synergistic effect. Taken together, these preclinical data demonstrate the potent activity of NVP-AUY922 against gastric cancer cells and offer a rationale for clinical development of the agent alone or in combination with other chemotherapeutic drugs to effectively treat gastric cancer.
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