Inhibitors of human histone deacetylase: synthesis and enzyme and cellular activity of straight chain hydroxamates.
Inhibitors of histone deacetylase (HDAC) have been shown to induce terminal differentiation of human tumor cell lines and to have antitumor effects in vivo. We have prepared analogues of suberoylanilide hydroxamic acid (SAHA) and trichostatin A and have evaluated them in a human HDAC enzyme inhibition assay, a p21(waf1) (p21) promoter assay, and in monolayer growth inhibition assays. One compound, 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]-benzamide, was found to affect the growth of a panel of eight human tumor cell lines differentially.
Remiszewski
Stacy W
SW
Sambucetti
Lidia C
LC
Atadja
Peter
P
Bair
Kenneth W
KW
Cornell
Wendy D
WD
Green
Michael A
MA
Howell
Kobporn Lulu
KL
Jung
Manfred
M
Kwon
Paul
P
Trogani
Nancy
N
Walker
Heather
H
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006898:Hydroxylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D011401:Promoter Regions, Genetic; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C448624:4-(dimethylamino)-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide; D000970:Antineoplastic Agents; D001549:Benzamides; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D006898:Hydroxylamines