title: Identification of a phenylacylsulfonamide series of dual Bcl-2/Bcl-xL antagonists.
abstract: A series of phenylacylsulfonamides has been prepared as antagonists of Bcl-2/Bcl-xL. In addition to potent binding affinities for both Bcl-2 and Bcl-xL, these compounds were shown to induce classical markers of apoptosis in isolated mitochondria. Overall weak cellular potency was improved by the incorporation of polar functionality resulting in compounds with moderate antiproliferative activity.
authors.affiliation: Bristol-Myers Squibb Research, PO Box 4000, Princeton, NJ 08543, USA. heidi.perez@bms.com
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Perez
authors.forename: Patrizia
authors.initials: P
authors.lastname: Banfi
authors.forename: Jay
authors.initials: J
authors.lastname: Bertrand
authors.forename: Zhen-Wei
authors.initials: ZW
authors.lastname: Cai
authors.forename: James W
authors.initials: JW
authors.lastname: Grebinski
authors.forename: Kyoung
authors.initials: K
authors.lastname: Kim
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lippy
authors.forename: Michele
authors.initials: M
authors.lastname: Modugno
authors.forename: Joseph
authors.initials: J
authors.lastname: Naglich
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schmidt
authors.forename: Andrew
authors.initials: A
authors.lastname: Tebben
authors.forename: Paola
authors.initials: P
authors.lastname: Vianello
authors.forename: Donna D
authors.initials: DD
authors.lastname: Wei
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.forename: Arturo
authors.initials: A
authors.lastname: Galvani
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Lombardo
authors.forename: Robert M
authors.initials: RM
authors.lastname: Borzilleri
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008958:Models, Molecular; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D013449:Sulfonamides; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D045304:Cytochromes c