title: Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin.
abstract: A series of hybrid compounds of bestatin (1) and actinonin (3), which promote degradation of cellular inhibitor of apoptosis protein 1 (cIAP1), were designed and synthesized. Structure-activity relationship studies indicated that absolute configuration, hydrophobicity at the alpha-position of the internal amide carbonyl group, and the presence of a small substituent at the alpha-position of the ester group are important factors for the expression of potent cIAP1 degradation-promoting activity. HAB-5A (30b) showed the most potent activity (IC(50)=0.53 microM) among the compounds prepared.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Tokyo 113-0032, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
authors.forename: Masashi
authors.initials: M
authors.lastname: Tetsuhashi
authors.forename: Keiko
authors.initials: K
authors.lastname: Sekine
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyachi
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Naito
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoyama
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D007930:Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013329:Structure-Activity Relationship
chemical_list: D006877:Hydroxamic Acids; D051034:Inhibitor of Apoptosis Proteins; D007930:Leucine; C012211:ubenimex; C010531:actinonin