title: Identification of N-(quinolin-8-yl)benzenesulfonamides as agents capable of down-regulating NFkappaB activity within two separate high-throughput screens of NFkappaB activation.
abstract: We describe here a series of N-(quinolin-8-yl)benzenesulfonamides capable of suppressing the NFkappaB pathway identified from two high-throughput screens run at two centers of the NIH Molecular Libraries Initiative. These small molecules were confirmed in both primary and secondary assays of NFkappaB activation and expanded upon through analogue synthesis. The series exhibited potencies in the cell-based assays at as low as 0.6 microM, and several indications suggest that the targeted activity lies within a common region of the NFkappaB pathway.
authors.affiliation: Division of Clinical Pharmacology & Experimental Therapeutics, Department of Medicine, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Xie
authors.forename: ShiXian
authors.initials: S
authors.lastname: Deng
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Thomas
authors.forename: Yidong
authors.initials: Y
authors.lastname: Liu
authors.forename: Ya-Qin
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Alison
authors.initials: A
authors.lastname: Rinderspacher
authors.forename: Wenwei
authors.initials: W
authors.lastname: Huang
authors.forename: Gangli
authors.initials: G
authors.lastname: Gong
authors.forename: Michael
authors.initials: M
authors.lastname: Wyler
authors.forename: Efithia
authors.initials: E
authors.lastname: Cayanis
authors.forename: Nathalie
authors.initials: N
authors.lastname: Aulner
authors.forename: Udo
authors.initials: U
authors.lastname: Többen
authors.forename: Caty
authors.initials: C
authors.lastname: Chung
authors.forename: Sergey
authors.initials: S
authors.lastname: Pampou
authors.forename: Noel
authors.initials: N
authors.lastname: Southall
authors.forename: Dusica
authors.initials: D
authors.lastname: Vidović
authors.forename: Stephan
authors.initials: S
authors.lastname: Schürer
authors.forename: Lars
authors.initials: L
authors.lastname: Branden
authors.forename: R Eric
authors.initials: RE
authors.lastname: Davis
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: James
authors.initials: J
authors.lastname: Inglese
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Austin
authors.forename: Donald W
authors.initials: DW
authors.lastname: Landry
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Smith
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Auld
mesh_terms: D020650:Combinatorial Chemistry Techniques; D015536:Down-Regulation / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D016328:NF-kappa B; D011804:Quinolines; D013449:Sulfonamides; D000096926:Benzenesulfonamides