Identification of N-(quinolin-8-yl)benzenesulfonamides as agents capable of down-regulating NFkappaB activity within two separate high-throughput screens of NFkappaB activation.
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.
Xie
Yuli
Y
Division of Clinical Pharmacology & Experimental Therapeutics, Department of Medicine, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
Deng
ShiXian
S
Thomas
Craig J
CJ
Liu
Yidong
Y
Zhang
Ya-Qin
YQ
Rinderspacher
Alison
A
Huang
Wenwei
W
Gong
Gangli
G
Wyler
Michael
M
Cayanis
Efithia
E
Aulner
Nathalie
N
Többen
Udo
U
Chung
Caty
C
Pampou
Sergey
S
Southall
Noel
N
Vidović
Dusica
D
Schürer
Stephan
S
Branden
Lars
L
Davis
R Eric
RE
Staudt
Louis M
LM
Inglese
James
J
Austin
Christopher P
CP
Landry
Donald W
DW
Smith
Deborah H
DH
Auld
Douglas S
DS
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
D016328:NF-kappa B; D011804:Quinolines; D013449:Sulfonamides; D000096926:Benzenesulfonamides