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Waterloo, Canada

Qin L.,China University of Technology | Yang F.,China University of Technology | Zhou C.,Amersino Biodevelop Inc. | Chen Y.,China University of Technology | And 4 more authors.
Journal of the American Chemical Society | Year: 2014

The aberrant interaction between p53 and Mdm2/MdmX is an attractive target for cancer drug discovery because the overexpression of Mdm2 and/or MdmX ultimately impairs the function of p53 in approximately half of all human cancers. Recent studies have shown that inhibition of both Mdm2 and MdmX is more efficient than that of a single target in promoting cellular apoptosis in cancers. In this study, we demonstrate that a dual small-molecule antagonist of Mdm2/MdmX can efficiently reactivate the p53 pathway in model cancer cells overexpressing MdmX and/or Mdm2. The dual antagonist was rationally designed based on segmental mutational analysis of the N-terminal domain of MdmX and the crystal structure of the N-terminal domain of Mdm2 in complex with nutlin-3a (an Mdm2-specific inhibitor). The current work establishes a small molecule therapeutic candidate that targets cancers overexpressing Mdm2 and/or MdmX. © 2014 American Chemical Society. Source

Li H.,Jinan University | Ma Y.,Jinan University | Chen Y.,Jinan University | Sang Y.,Jinan University | And 7 more authors.
Angewandte Chemie - International Edition | Year: 2010

(Figure Presented) A polypeptide containing an albuminbinding domain (ABD), an amino acid sequence linker, and glucagon-like peptide-1 (GLP-1), a potential antidiabetic agent, is designed to slowly release GLP-1 through sequential cleavage by native plasma proteases (see picture). The halflife of the polypeptide in the bloodstream is extended by its association with human serum albumin (HSA). © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

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