Discovery of a 6-(pyridin-3-yl)benzo[d]thiazole template for optimization of hedgehog and PI3K/AKT/mTOR dual inhibitors

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 r...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2015-09, Vol.25 (17), p.3665-3670
Hauptverfasser:	Yang, Zhaohui, Ma, Haikuo, Sun, Zhijian, Luo, Lusong, Tian, Sheng, Zheng, Jiyue, Zhang, Xiaohu
Format:	Artikel
Sprache:	eng
Schlagworte:	Anilides - chemistry Anilides - pharmacology Animals Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Cancer therapy Drug Design Drug Discovery Drug Screening Assays, Antitumor - methods GPCR Hedgehog pathway Hedgehog Proteins - antagonists & inhibitors Humans Kinase Mice Molecular Targeted Therapy - methods NIH 3T3 Cells - drug effects Phosphatidylinositol 3-Kinases - antagonists & inhibitors PI3K/AKT/mTOR pathway Polypharmacology Proto-Oncogene Proteins c-akt - antagonists & inhibitors Pyridines - chemistry Pyridines - pharmacology Structure-Activity Relationship Thiazoles - chemistry TOR Serine-Threonine Kinases - antagonists & inhibitors
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