强效非肽类Smac模拟物/XIAP抑制剂作为癌症治疗促凋亡药物的合理设计、合成及表征
Rational design, synthesis and characterization of potent, non-peptidic Smac mimics/XIAP inhibitors as proapoptotic agents for cancer therapy.
作者信息
Seneci Pierfausto, Bianchi Aldo, Battaglia Cristina, Belvisi Laura, Bolognesi Martino, Caprini Andrea, Cossu Federica, Franco Elena de, Matteo Marilenia de, Delia Domenico, Drago Carmelo, Khaled Amira, Lecis Daniele, Manzoni Leonardo, Marizzoni Moira, Mastrangelo Eloise, Milani Mario, Motto Ilaria, Moroni Elisabetta, Potenza Donatella, Rizzo Vincenzo, Servida Federica, Turlizzi Elisa, Varrone Maurizio, Vasile Francesca, Scolastico Carlo
机构信息
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, Milan, Italy.
出版信息
Bioorg Med Chem. 2009 Aug 15;17(16):5834-56. doi: 10.1016/j.bmc.2009.07.009. Epub 2009 Jul 10.
Novel proapoptotic Smac mimics/IAPs inhibitors have been designed, synthesized and characterized. Computational models and structural studies (crystallography, NMR) have elucidated the SAR of this class of inhibitors, and have permitted further optimization of their properties. In vitro characterization (XIAP BIR3 and linker-BIR2-BIR3 binding, cytotox assays, early ADMET profiling) of the compounds has been performed, identifying one lead for further in vitro and in vivo evaluation.
新型促凋亡Smac模拟物/IAPs抑制剂已被设计、合成和表征。计算模型和结构研究（晶体学、核磁共振）阐明了这类抑制剂的构效关系，并使其性质得到进一步优化。已对这些化合物进行了体外表征（XIAP BIR3和接头-BIR2-BIR3结合、细胞毒性测定、早期药物代谢动力学/药物毒性预测分析），确定了一个先导化合物用于进一步的体外和体内评估。
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