Discovery of 2-(4-methylfuran-2(5H)-ylidene)malononitrile and thieno[3,2-b]thiophene-2-carboxylic acid derivatives as G protein-coupled receptor 35 (GPR35) agonists.
作者： Huayun Deng , Haibei Hu , Mingqian He , Jieyu Hu , Weijun Niu
DOI: 10.1021/JM200999F
关键词: Carboxylic acid 、 Beta-Arrestins 、 Malononitrile 、 Agonist 、 G-Protein Coupled Receptor 35 、 Stereochemistry 、 GPR35 、 Structure–activity relationship 、 Chemistry 、 Zaprinast
摘要: Screening with dynamic mass redistribution (DMR) assays in a native cell line HT-29 led to identification of two novel series chemical compounds, 2-(4-methylfuran-2(5H)-ylidene)malononitrile and thieno[3,2-b]thiophene-2-carboxylic acid derivatives, as GPR35 agonists. Of these, 2-(3-cyano-5-(3,4-dichlorophenyl)-4,5-dimethylfuran-2(5H)-ylidene)malononitrile (YE120) 6-bromo-3-methylthieno[3,2-b]thiophene-2-carboxylic (YE210) were found be the most potent agonists an EC50 32.5 ± 1.7 nM 63.7 4.1 nM, respectively. Both exhibited better potency than that zaprinast, known agonist. DMR antagonist assays, knockdown interference RNA, receptor internalization Tango β-arrestin translocation confirmed agonist activity these ligands is specific GPR35. The present study provides starting point for further investigations biology pharmacology.
acs.org
sci-hub.se 参考文章(26)
Cristina Cosi, Guido Mannaioni, Andrea Cozzi, Vincenzo Carlà, Maria Sili, Leonardo Cavone, Dario Maratea, Flavio Moroni, G-protein coupled receptor 35 (GPR35) activation and inflammatory pain: Studies on the antinociceptive effects of kynurenic acid and zaprinast Neuropharmacology. ,vol. 60, pp. 1227- 1231 ,(2011) , 10.1016/J.NEUROPHARM.2010.11.014
Jinghong Wang, Nicole Simonavicius, Xiaosu Wu, Gayathri Swaminath, Jeff Reagan, Hui Tian, Lei Ling, Kynurenic Acid as a Ligand for Orphan G Protein-coupled Receptor GPR35 Journal of Biological Chemistry. ,vol. 281, pp. 22021- 22028 ,(2006) , 10.1074/JBC.M603503200
Kyung-Duk Min, Masanori Asakura, Yulin Liao, Kenji Nakamaru, Hidetoshi Okazaki, Tomoko Takahashi, Kazunori Fujimoto, Shin Ito, Ayako Takahashi, Hiroshi Asanuma, Satoru Yamazaki, Tetsuo Minamino, Shoji Sanada, Osamu Seguchi, Atsushi Nakano, Yosuke Ando, Toshiaki Otsuka, Hidehiko Furukawa, Tadashi Isomura, Seiji Takashima, Naoki Mochizuki, Masafumi Kitakaze, Identification of genes related to heart failure using global gene expression profiling of human failing myocardium. Biochemical and Biophysical Research Communications. ,vol. 393, pp. 55- 60 ,(2010) , 10.1016/J.BBRC.2010.01.076
Saori Oka, Ryo Ota, Mitsuru Shima, Atsushi Yamashita, Takayuki Sugiura, GPR35 is a novel lysophosphatidic acid receptor. Biochemical and Biophysical Research Communications. ,vol. 395, pp. 232- 237 ,(2010) , 10.1016/J.BBRC.2010.03.169
Ye Fang, Ann M. Ferrie, Norman H. Fontaine, Po Ki Yuen, Characteristics of dynamic mass redistribution of epidermal growth factor receptor signaling in living cells measured with label-free optical biosensors. Analytical Chemistry. ,vol. 77, pp. 5720- 5725 ,(2005) , 10.1021/AC050887N
Ralf Schröder, Nicole Janssen, Johannes Schmidt, Anna Kebig, Nicole Merten, Stephanie Hennen, Anke Müller, Stefanie Blättermann, Marion Mohr-Andrä, Sabine Zahn, Jörg Wenzel, Nicola J Smith, Jesús Gomeza, Christel Drewke, Graeme Milligan, Klaus Mohr, Evi Kostenis, Deconvolution of complex G protein-coupled receptor signaling in live cells using dynamic mass redistribution measurements Nature Biotechnology. ,vol. 28, pp. 943- 949 ,(2010) , 10.1038/NBT.1671
Richard B. Mailman, GPCR functional selectivity has therapeutic impact Trends in Pharmacological Sciences. ,vol. 28, pp. 390- 396 ,(2007) , 10.1016/J.TIPS.2007.06.002
Vasiliy Goral, Yan Jin, Haiyan Sun, Ann M. Ferrie, Qi Wu, Ye Fang, Agonist-Directed Desensitization of the β2-Adrenergic Receptor PLoS ONE. ,vol. 6, pp. e19282- ,(2011) , 10.1371/JOURNAL.PONE.0019282
Steven J Charlton, Agonist efficacy and receptor desensitization: from partial truths to a fuller picture. British Journal of Pharmacology. ,vol. 158, pp. 165- 168 ,(2009) , 10.1111/J.1476-5381.2009.00352.X
Yan V. Sun, Lawrence F. Bielak, Patricia A. Peyser, Stephen T. Turner, Patrick F. Sheedy, Eric Boerwinkle, Sharon L.R. Kardia, Application of machine learning algorithms to predict coronary artery calcification with a sibship-based design Genetic Epidemiology. ,vol. 32, pp. 350- 360 ,(2008) , 10.1002/GEPI.20309