70965-24-1Relevant articles and documents
Scaffold Hopping and Optimization of Maleimide Based Porcupine Inhibitors
Ho, Soo Yei,Alam, Jenefer,Jeyaraj, Duraiswamy Athisayamani,Wang, Weiling,Lin, Grace Ruiting,Ang, Shi Hua,Tan, Eldwin Sum Wai,Lee, May Ann,Ke, Zhiyuan,Madan, Babita,Virshup, David M.,Ding, Li Jun,Manoharan, Vithya,Chew, Yun Shan,Low, Choon Bing,Pendharkar, Vishal,Sangthongpitag, Kanda,Hill, Jeffrey,Keller, Thomas H.,Poulsen, Anders
, p. 6678 - 6692 (2017/08/18)
Porcupine is an O-acyltransferase that regulates Wnt secretion. Inhibiting porcupine may block the Wnt pathway which is often dysregulated in various cancers. Consequently porcupine inhibitors are thought to be promising oncology therapeutics. A high throughput screen against porcupine revealed several potent hits that were confirmed to be Wnt pathway inhibitors in secondary assays. We developed a pharmacophore model and used the putative bioactive conformation of a xanthine inhibitor for scaffold hopping. The resulting maleimide scaffold was optimized to subnanomolar potency while retaining good physical druglike properties. A preclinical development candidate was selected for which extensive in vitro and in vivo profiling is reported.
BIOMIMETIC, CHEMICAL, AND SPECTROSCOPIC EVALUATIONS FOR THE RADIOSENSITIZING POTENTIAL OF N1- AND N2-SUBSTITUTED DERIVATIVES OF 3-NITRO-1,2,4-TRIAZOLE TOWARD HYPOXIC CELLS IN THE RADIOTHERAPY: REMARKABLY DIFFERENT SUBSTITUTION EFFECT
Nagao, Yoshimitsu,Sano, Shigeki,Oxhiai, Masahito,Fujita, Eichi
, p. 3211 - 3232 (2007/10/02)
N1- and N2-derivatives of 3-nitro-1,2,4-triazole (3-NTR) were subjected to the non-biological evaluation methods involving biomimetic, chemical, and spectroscopic procedures for the radiosensitizing potential.Consequently, the N1-derivatives of 3-NTR were suggested to be more promising radiosensitizers to hypoxic cells in vivo than the N2-derivatives.
