Rational design, synthesis and characterization of potent, non-peptidic Smac mimics/XIAP inhibitors as proapoptotic agents for cancer therapy

Pierfausto Seneci, Aldo Bianchi, Cristina Battaglia, Laura Belvisi, Martino Bolognesi, Andrea Caprini, Federica Cossu, Elena de Franco, Marilenia de Matteo, Domenico Delia, Carmelo Drago, Amira Khaled, Daniele Lecis, Leonardo Manzoni, Moira Marizzoni, Eloise Mastrangelo, Mario Milani, Ilaria Motto, Elisabetta Moroni, Donatella PotenzaVincenzo Rizzo, Federica Servida, Elisa Turlizzi, Maurizio Varrone, Francesca Vasile, Carlo Scolastico

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)5834-5856
Number of pages23
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number16
DOIs
Publication statusPublished - Aug 15 2009

Keywords

  • Apoptosis
  • Crystallography
  • Medicinal chemistry
  • NMR
  • Oncology
  • Rational drug design
  • Smac
  • XIAP

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Fingerprint

Dive into the research topics of 'Rational design, synthesis and characterization of potent, non-peptidic Smac mimics/XIAP inhibitors as proapoptotic agents for cancer therapy'. Together they form a unique fingerprint.

Cite this