title: Discovery and structure-activity relationship of 2-phenyl-oxazole-4-carboxamide derivatives as potent apoptosis inducers.
abstract: As a continuation of our efforts to discover novel apoptosis inducers as anticancer agents using a cell-based caspase HTS assay, 2-phenyl-oxazole-4-carboxamide derivatives were identified. The structure-activity relationships of this class of molecules were explored. Compound 1k, with EC(50) of 270 nM and GI(50) of 229 nM in human colorectal DLD-1 cells, was selected and demonstrated the ability to cleave PARP and displayed DNA laddering, the hallmarks of apoptosis. Compound 1k showed 63% tumor growth inhibition in human colorectal DLD-1 xenograft mouse model at 50 mpk, bid.
authors.affiliation: Celera Genomics, South San Francisco, CA 94080, USA. vince.tai@gmail.com
authors.forename: Vincent W-F
authors.initials: VW
authors.lastname: Tai
authors.forename: David
authors.initials: D
authors.lastname: Sperandio
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Shelton
authors.forename: Joane
authors.initials: J
authors.lastname: Litvak
authors.forename: Keith
authors.initials: K
authors.lastname: Pararajasingham
authors.forename: Ben
authors.initials: B
authors.lastname: Cebon
authors.forename: Julia
authors.initials: J
authors.lastname: Lohman
authors.forename: John
authors.initials: J
authors.lastname: Eksterowicz
authors.forename: Seema
authors.initials: S
authors.lastname: Kantak
authors.forename: Peter
authors.initials: P
authors.lastname: Sabbatini
authors.forename: Cindy
authors.initials: C
authors.lastname: Brown
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zeitz
authors.forename: Chris
authors.initials: C
authors.lastname: Reed
authors.forename: Bill
authors.initials: B
authors.lastname: Maske
authors.forename: Doris
authors.initials: D
authors.lastname: Graupe
authors.forename: Alberto
authors.initials: A
authors.lastname: Estevez
authors.forename: Jason
authors.initials: J
authors.lastname: Oeh
authors.forename: Darren
authors.initials: D
authors.lastname: Wong
authors.forename: Yong
authors.initials: Y
authors.lastname: Ni
authors.forename: Paul
authors.initials: P
authors.lastname: Sprengeler
authors.forename: Robert
authors.initials: R
authors.lastname: Yee
authors.forename: Catherine
authors.initials: C
authors.lastname: Magill
authors.forename: Anthony
authors.initials: A
authors.lastname: Neri
authors.forename: Sui Xiong
authors.initials: SX
authors.lastname: Cai
authors.forename: John
authors.initials: J
authors.lastname: Drewe
authors.forename: Ling
authors.initials: L
authors.lastname: Qiu
authors.forename: John
authors.initials: J
authors.lastname: Herich
authors.forename: Ben
authors.initials: B
authors.lastname: Tseng
authors.forename: Shailaja
authors.initials: S
authors.lastname: Kasibhatla
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Spencer
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000577:Amides; D010080:Oxazoles