CUDC-101, a multitargeted inhibitor of histone deacetylase and human epidermal growth factor receptor 2, exerts potent anticancer activity

Lai CJ;Bao R;Tao X;Wang J;Atoyan R;Qu H;Wang DG;Yin L;Samson M;Forrester J;Zifcak B;Xu GX;DellaRocca S;Zhai HX;Cai X;Munger WE;Keegan M;Pepicelli CV;Qian C “Cancer research” 2010

Receptor tyrosine kinase inhibitors recently become important therapeuticsfor your a number of cancers. However, mainly because of the heterogeneous and dynamic nature of tumors, the advantages of these agents is oftentimes hindered by poor response rates and acquired drug resistance. To overpower these limitations, weresulted in a novel small molecule, CUDC-101, which simultaneously inhibits histone deacetylase along with the receptor kinases epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in cancer cells. Simply because of its integrated histone deacetylase inhibition, CUDC-101 synergistically blocked key regulators of EGFR/HER2 signaling pathways, also attenuating multiple compensatory pathways,for instance AKT, HER3, and MET, which enable cancer cells to emerge from the consequences of conventional EGFR/HER2 inhibitors. CUDC-101 displayed potent antiproliferative and proapoptotic activities against cultured and implanted tumor cells that happen to be sensitive orproof against several approved single-targeted drugs. Our resultsdemonstrate that CUDC-101provides the possible ways to dramatically increase the remedy for heterogeneous and drug-resistant tumors that can not be controlled with single-target agents. Further,they furnish a frameworkto build individual small molecules that simultaneously antagonize multiple biochemically distinct oncogenic targets, suggesting a comprehensive paradigm to surpass conventional, single-target cancer therapeutics.


CUDC-101, epidermal growth factor receptor (EGFR)

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