Discovery of a 6-(pyridin-3-yl)benzo[d]thiazole template for optimization of hedgehog and PI3K/AKT/mTOR dual inhibitors. Issue 17 (1st September 2015)

• Record Type: Journal Article
• Authors: Yang, Zhaohui; Ma, Haikuo; Sun, Zhijian; Luo, Lusong; Tian, Sheng; Zheng, Jiyue; Zhang, Xiaohu
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 17(2015)
• Page Start: 3665
• Page End: 3670
• Publication Date: 2015-09-01
• Subjects: Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.06.049
• Languages: English
• ISSNs: 0960-894X

Abstract

<abstract xml:lang="en" abstract-type="graphical" id="ab005"> <title id="st005">Graphical abstract</title> <sec> <p id="sp0005">Vismodegib is the first FDA approved cancer therapy based on inhibition of aberrant hedgehog signaling. Like most cancer therapies, vismodegib suffered from resistance, even during clinical development. Numerous reports demonstrated that simultaneous blockage of hedgehog and PI3K/AKT/mTOR pathways resulted in significantly superior outcomes compared with single agent alone in a number of animal disease models. The dual hedgehog and PI3K/AKT/mTOR inhibition represented a promising approach not only to overcoming the resistance but also to delaying its onset. Here we report a series of compounds based on a 6-(pyridin-3-yl)benzo[<italic>d</italic>]thiazole template which have demonstrated significant inhibition of both hedgehog and PI3K/AKT/mTOR signaling pathways. This new scaffold can serve as a lead for further optimization. <fig id="f0025" position="anchor"><graphic position="anchor" xlink:href="ark:/27927/pgj28j8q5rd" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></fig></p> </sec> </abstract>