A novel series of potent and selective ketone histone deacetylase inhibitors with antitumor activity in vivo.
Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer therapy, and the first generation HDAC inhibitors are currently in the clinic. Entirely novel ketone HDAC inhibitors have been developed from the cyclic tetrapeptide apicidin. These compounds show class I subtype selectivity and levels of cellular activity comparable to clinical candidates. A representative example has demonstrated tumor growth inhibition in a human colon HCT-116 carcinoma xenograft model comparable to known inhibitors.
Jones
Philip
P
IRBM/Merck Research Laboratories, Via Pontina km 30,600, 00040 Pomezia, Italy. philip_jones@merck.com
Altamura
Sergio
S
De Francesco
Raffaele
R
Paz
Odalys Gonzalez
OG
Kinzel
Olaf
O
Mesiti
Giuseppe
G
Monteagudo
Edith
E
Pescatore
Giovanna
G
Rowley
Michael
M
Verdirame
Maria
M
Steinkühler
Christian
C
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000737:chemistry; D006801:Humans; D007659:Ketones / Q000494:pharmacology*; D015394:Molecular Structure
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D007659:Ketones; D006655:Histone Deacetylases