title: Rational design, synthesis and characterization of potent, non-peptidic Smac mimics/XIAP inhibitors as proapoptotic agents for cancer therapy.
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.
authors.affiliation: Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, Milan, Italy. pierfausto.seneci@unimi.it
authors.forename: Pierfausto
authors.initials: P
authors.lastname: Seneci
authors.forename: Aldo
authors.initials: A
authors.lastname: Bianchi
authors.forename: Cristina
authors.initials: C
authors.lastname: Battaglia
authors.forename: Laura
authors.initials: L
authors.lastname: Belvisi
authors.forename: Martino
authors.initials: M
authors.lastname: Bolognesi
authors.forename: Andrea
authors.initials: A
authors.lastname: Caprini
authors.forename: Federica
authors.initials: F
authors.lastname: Cossu
authors.forename: Elena de
authors.initials: Ed
authors.lastname: Franco
authors.forename: Marilenia de
authors.initials: Md
authors.lastname: Matteo
authors.forename: Domenico
authors.initials: D
authors.lastname: Delia
authors.forename: Carmelo
authors.initials: C
authors.lastname: Drago
authors.forename: Amira
authors.initials: A
authors.lastname: Khaled
authors.forename: Daniele
authors.initials: D
authors.lastname: Lecis
authors.forename: Leonardo
authors.initials: L
authors.lastname: Manzoni
authors.forename: Moira
authors.initials: M
authors.lastname: Marizzoni
authors.forename: Eloise
authors.initials: E
authors.lastname: Mastrangelo
authors.forename: Mario
authors.initials: M
authors.lastname: Milani
authors.forename: Ilaria
authors.initials: I
authors.lastname: Motto
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Moroni
authors.forename: Donatella
authors.initials: D
authors.lastname: Potenza
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Rizzo
authors.forename: Federica
authors.initials: F
authors.lastname: Servida
authors.forename: Elisa
authors.initials: E
authors.lastname: Turlizzi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Varrone
authors.forename: Francesca
authors.initials: F
authors.lastname: Vasile
authors.forename: Carlo
authors.initials: C
authors.lastname: Scolastico
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D051017:Apoptosis Regulatory Proteins; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001643:Bridged Bicyclo Compounds; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C516925:bicyclo(5.3.0)decane