Identification of long chain alkylidenemalonates as novel small molecule modulators of histone acetyltransferases.
Pentadecylidenemalonate 1b, a simplified analogue of anacardic acid, was identified as the first mixed activator/inhibitor of histone acetyltransferases (HATs). It potentiates PCAF HAT activity while inhibiting those of p300/CBP and recombinant CBP. The remarkable apoptotic effect together with the ability to selectively acetylate histone versus non-histone substrates appoint 1b as a lead for the development of anticancer drugs.
Sbardella
Gianluca
G
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy. gsbardella@unisa.it
Castellano
Sabrina
S
Vicidomini
Caterina
C
Rotili
Dante
D
Nebbioso
Angela
A
Miceli
Marco
M
Altucci
Lucia
L
Mai
Antonello
A
D000107:Acetylation; D000466:Alkadienes / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors*; D006801:Humans; D008314:Malonates / Q000737:chemistry*; D008956:Models, Chemical; D020298:U937 Cells; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors; D000099224:p300-CBP-Associated Factor
D000466:Alkadienes; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D051548:Histone Acetyltransferases; D008314:Malonates; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C000591545:pentadecylidenemalonate 1b