共查询到20条相似文献,搜索用时 15 毫秒
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Zufeng Guo Zhiqiang Cheng Jingxin Wang Wukun Liu Hanjing Peng Yuefan Wang A. V. Subba Rao Ruo‐jing Li Xue Ying Preethi Korangath Maria V. Liberti Yingjun Li Yongmei Xie Sam Y. Hong Cordelia Schiene‐Fischer Gunter Fischer Jason W. Locasale Saraswati Sukumar Heng Zhu Jun O. Liu 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(48):17318-17322
Glucose transporters play an essential role in cancer cell proliferation and survival and have been pursued as promising cancer drug targets. Using microarrays of a library of new macrocycles known as rapafucins, which were inspired by the natural product rapamycin, we screened for new inhibitors of GLUT1. We identified multiple hits from the rapafucin 3D microarray and confirmed one hit as a bona fide GLUT1 ligand, which we named rapaglutin A (RgA). We demonstrate that RgA is a potent inhibitor of GLUT1 as well as GLUT3 and GLUT4, with an IC50 value of low nanomolar for GLUT1. RgA was found to inhibit glucose uptake, leading to a decrease in cellular ATP synthesis, activation of AMP‐dependent kinase, inhibition of mTOR signaling, and induction of cell‐cycle arrest and apoptosis in cancer cells. Moreover, RgA was capable of inhibiting tumor xenografts in vivo without obvious side effects. RgA could thus be a new chemical tool to study GLUT function and a promising lead for developing anticancer drugs. 相似文献
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Judith Staerk Costas A. Lyssiotis Lea A. Medeiro Michael Bollong Ruth K. Foreman Shoutian Zhu Michael Garcia Qing Gao Laure C. Bouchez Luke L. Lairson Bradley D. Charette Lubica Supekova Jeffrey Janes Achim Brinker Charles Y. Cho Rudolf Jaenisch Peter G. Schultz 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2011,123(25):5852-5854
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Vclav Nmec Michaela Hylsov Luk Maier Jana Flegel Sonja Sievers Slava Ziegler Martin Schrder Benedict‐Tilman Berger Apirat Chaikuad Barbora Val
íkov Stjepan Uldrijan Stanislav Drpela Karel Sou
ek Herbert Waldmann Stefan Knapp Kamil Paruch 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(4):1074-1078
Reported is the identification of the furo[3,2‐b]pyridine core as a novel scaffold for potent and highly selective inhibitors of cdc‐like kinases (CLKs) and efficient modulators of the Hedgehog signaling pathway. Initially, a diverse target compound set was prepared by synthetic sequences based on chemoselective metal‐mediated couplings, including assembly of the furo[3,2‐b]pyridine scaffold by copper‐mediated oxidative cyclization. Optimization of the subseries containing 3,5‐disubstituted furo[3,2‐b]pyridines afforded potent, cell‐active, and highly selective inhibitors of CLKs. Profiling of the kinase‐inactive subset of 3,5,7‐trisubstituted furo[3,2‐b]pyridines revealed sub‐micromolar modulators of the Hedgehog pathway. 相似文献