885012-40-8Relevant academic research and scientific papers
Development of novel dual binders as potent, selective, and orally bioavailable tankyrase inhibitors
Hua, Zihao,Bregman, Howard,Buchanan, John L.,Chakka, Nagasree,Guzman-Perez, Angel,Gunaydin, Hakan,Huang, Xin,Gu, Yan,Berry, Virginia,Liu, Jingzhou,Teffera, Yohannes,Huang, Liyue,Egge, Bryan,Emkey, Renee,Mullady, Erin L.,Schneider, Steve,Andrews, Paul S.,Acquaviva, Lisa,Dovey, Jennifer,Mishra, Ankita,Newcomb, John,Saffran, Douglas,Serafino, Randy,Strathdee, Craig A.,Turci, Susan M.,Stanton, Mary,Wilson, Cindy,Dimauro, Erin F.
, p. 10003 - 10015 (2014/01/17)
Tankyrases (TNKS1 and TNKS2) are proteins in the poly ADP-ribose polymerase (PARP) family. They have been shown to directly bind to axin proteins, which negatively regulate the Wnt pathway by promoting β-catenin degradation. Inhibition of tankyrases may offer a novel approach to the treatment of APC-mutant colorectal cancer. Hit compound 8 was identified as an inhibitor of tankyrases through a combination of substructure searching of the Amgen compound collection based on a minimal binding pharmacophore hypothesis and high-throughput screening. Herein we report the structure- and property-based optimization of compound 8 leading to the identification of more potent and selective tankyrase inhibitors 22 and 49 with improved pharmacokinetic properties in rodents, which are well suited as tool compounds for further in vivo validation studies.
Orally bioavailable potent soluble epoxide hydrolase inhibitors
Sung, Hee Hwang,Tsai, Hsing-Ju,Liu, Jun-Yan,Morisseau, Christophe,Hammock, Bruce D.
, p. 3825 - 3840 (2008/02/13)
A series of N,N′-disubstituted ureas having a conformationally restricted cis- or trans-1,4-cyclohexane α to the urea were prepared and tested as soluble epoxide hydrolase (sEH) inhibitors. This series of compounds showed low nanomolar to picomolar activi
IMPROVED INHIBITORS FOR THE SOLUBLE EPOXIDE HYDROLASE
-
Page/Page column 72, (2010/11/08)
Inhibitors of the soluble epoxide hydrolase (sEH) are provided that incorporate multiple pharmacophores and are useful in the treatment of diseases
