@article{APS9921,
author = {Qing-rou Li and Hui Zhao and Xue-sai Zhang and Henk Lang and Ker Yu},
title = {Novel-smoothened inhibitors for therapeutic targeting of naïve and drug-resistant hedgehog pathway-driven cancers},
journal = {Acta Pharmacologica Sinica},
volume = {40},
number = {2},
year = {2019},
keywords = {},
abstract = {The G protein-coupled receptor (GPCR) smoothened (SMO) is a key signaling component of the sonic hedgehog (Hh) pathway and a clinically validated target for cancer treatment. The FDA-approved SMO inhibitors GDC-0449/Vismodegib and LDE225/Sonidegib demonstrated clinical antitumor efficacy. Nevertheless, relatively high percentage of treated patients would eventually develop acquired cross resistance to both drugs. Here, based on published structure and activity of GDC-0449 inhibitor class, we replaced its amide core with benzimidazole which retained bulk of the SMO-targeting activity as measured in our Hh/SMO/Gli1-reporter system. Synthesis and screening of multiple series of benzimidazole derivatives identified HH-1, HH-13, and HH-20 with potent target suppression (IC50: },
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/9921}
}