Alpha-keto amides as inhibitors of histone deacetylase.
Alpha-keto ester and amides were found to be potent inhibitors of histone deacetylase. Nanomolar inhibitors against the isolated enzyme and sub-micromolar inhibitors of cellular proliferation were obtained. The alpha-keto amide 30 also exhibited significant anti-tumor effects in an in vivo tumor model.
Wada
Carol K
CK
Cancer Research, Abbott Laboratories, Department R47J, Bldg. AP10, 100 Abbott Park Road, Abbott Park, IL 60064, USA. carol.wada@abbott.com
Frey
Robin R
RR
Ji
Zhiqin
Z
Curtin
Michael L
ML
Garland
Robert B
RB
Holms
James H
JH
Li
Junling
J
Pease
Lori J
LJ
Guo
Jun
J
Glaser
Keith B
KB
Marcotte
Patrick A
PA
Richardson
Paul L
PL
Murphy
Shannon S
SS
Bouska
Jennifer J
JJ
Tapang
Paul
P
Magoc
Terrance J
TJ
Albert
Daniel H
DH
Davidsen
Steven K
SK
Michaelides
Michael R
MR
D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051379:Mice; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000577:Amides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases