619325-13-2Relevant academic research and scientific papers
N-Hydroxy-3-phenyl-2-propenamides as novel inhibitors of human histone deacetylase with in vivo antitumor activity: Discovery of (2E)-N-hydroxy-3-[4-[[(2-hydroxyethyl)[2-(1H-indol-3-yl)ethyl] amino]methyl]-phenyl]-2-propenamide (NVP-LAQ824)
Remiszewski, Stacy W.,Sambucetti, Lidia C.,Bair, Kenneth W.,Bontempo, John,Cesarz, David,Chandramouli, Nagarajan,Chen, Ru,Cheung, Min,Cornell-Kennon, Susan,Dean, Karl,Diamantidis, George,France, Dennis,Green, Michael A.,Howell, Kobporn Lulu,Kashi, Rina,Kwon, Paul,Lassota, Peter,Martin, Mary S.,Mou, Yin,Perez, Lawrence B.,Sharma, Sushil,Smith, Troy,Sorensen, Eric,Taplin, Francis,Trogani, Nancy,Versace, Richard,Walker, Heather,Weltchek-Engler, Susan,Wood, Alexander,Wu, Arthur,Atadja, Peter
, p. 4609 - 4624 (2007/10/03)
A series of N-hydroxy-3-phenyl-2-propenamides were prepared as novel inhibitors of human histone deacetylase (HDAC). These compounds were potent enzyme inhibitors, having IC50s 50 750 nM were tested for maximum tolerated dose (MTD) and for efficacy in the HCT116 human colon tumor xenograft assay. Four compounds having an MTD ≥ 100 mg/kg were selected for dose-response studies in the HCT116 xenograft model. One compound, 9 (NVP-LAQ824), had significant dose-related activity in the HCT116 colon and A549 lung tumor models, high MTD, and low gross toxicity. On the basis, in part, of these properties, 9 has entered human clinical trials in 2002.
