title: Design, synthesis, and characterization of new embelin derivatives as potent inhibitors of X-linked inhibitor of apoptosis protein.
abstract: X-Linked inhibitor of apoptosis protein (XIAP) is a promising molecular target for the design of new anticancer drugs aiming at promoting apoptosis in cancer cells. We have previously identified embelin as an inhibitor of XIAP through computational structure-based database screening. Herein, we report the design, synthesis, and evaluation of new embelin analogues as inhibitors of XIAP. Our efforts led to the identification of new and more potent inhibitors. For example, compound 6g has a Ki value of 180 nM binding to XIAP BIR3, in a competitive binding assay and represents a promising lead compound for further optimization.
authors.affiliation: Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Chen
authors.forename: Zaneta
authors.initials: Z
authors.lastname: Nikolovska-Coleska
authors.forename: Guoping
authors.initials: G
authors.lastname: Wang
authors.forename: Su
authors.initials: S
authors.lastname: Qiu
authors.forename: Shaomeng
authors.initials: S
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D003198:Computer Simulation; D016208:Databases, Factual; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D013329:Structure-Activity Relationship; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D051636:X-Linked Inhibitor of Apoptosis Protein; C010945:embelin