404951-55-9Relevant academic research and scientific papers
Structure-Based Design of Potent Nicotinamide Phosphoribosyltransferase Inhibitors with Promising in Vitro and in Vivo Antitumor Activities
Bai, Jinhong,Liao, Chenzhong,Liu, Yanghan,Qin, Xiaochu,Chen, Jiaxuan,Qiu, Yatao,Qin, Dongguang,Li, Zheng,Tu, Zheng-Chao,Jiang, Sheng
, p. 5766 - 5779 (2016)
Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) has the potential to directly limit NAD production in cancer cells and is an effective strategy for cancer treatment. Using a structure-based strategy, we have designed a new class of potent small-molecule inhibitors of NAMPT. Several designed compounds showed promising antiproliferative activities in vitro. (E)-N-(5-((4-(((2-(1H-Indol-3-yl)ethyl)(isopropyl)amino)methyl)phenyl)amino)pentyl)-3-(pyridin-3-yl)acrylamide, 30, bearing an indole moiety, has an IC50 of 25.3 nM for binding to the NAMPT protein and demonstrated promising inhibitory activities in the nanomolar range against several cancer cell lines (MCF-7 GI50 = 0.13 nM; MDA-MB-231 GI50 = 0.15 nM). Triple-negative breast cancer is the most malignant subtype of breast cancer with no effective targeted treatments currently available. Significant antitumor efficacy of compound 30 was achieved (TGI was 73.8%) in an orthotopic MDA-MB-231 triple-negative breast cancer xenograft tumor model. This paper reports promising lead molecules for the inhibition of NAMPT which could serve as a basis for further investigation.
SELECTIVE HISTONE DEACETYLASE (HDAC) DEGRADERS AND METHODS OF USE THEREOF
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Paragraph 0120-0122, (2021/05/15)
The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions mediated by aberrant histone deacetylase (HCADC) (e.g., HDAC3) activity.
SELECTIVE DUAL HISTONE DEACETYLASE 6/8 (HDAC6/8) DEGRADERS AND METHODS OF USE THEREOF
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Paragraph 00120-00122, (2021/05/15)
The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions mediated by aberrant histone deacetylases 6 and 8 (HDAC6/8) activity.
METHOD OF USE OF DEACETYLASE INHIBITORS
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Page/Page column 24-25, (2008/06/13)
The present invention provides methods of treating and/or preventing pathologic cardiac hypertrophy and heart failure comprising administering hydroxamate compounds which are deacetylase inhibitors.
INHIBITORS OF HISTONE DEACETYLASE
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Page/Page column 49-50, (2010/02/14)
The invention relates to a series of compounds useful for inhibiting histone deacetylase (HDAC) enzymatic activity. The invention also provides a method for inhibiting histone descetylase in a cell using said compounds as well as a method for treating cell proliferative diseases and conditions using said HDAC inhibitors. Further, the invention provides pharmaceutical compositions comprising the HDAC inhibiting compounds and a pharmaceutically acceptable carrier.
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.
