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Autotaxin inhibitors: a patent review

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Pages 1123-1132 | Published online: 06 May 2013

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Zehui Tan, Hongrui Lei, Ming Guo, Yuxiang Chen & Xin Zhai. (2021) An updated patent review of autotaxin inhibitors (2017–present). Expert Opinion on Therapeutic Patents 31:5, pages 421-434.
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Patrick Mathieu, Benoit J. Arsenault, Marie-Chloé Boulanger, Yohan Bossé & Marlys L. Koschinsky. (2017) Pathobiology of Lp(a) in calcific aortic valve disease. Expert Review of Cardiovascular Therapy 15:10, pages 797-807.
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Aikaterini Nikolaou, Maroula G. Kokotou, Dimitris Limnios, Anastasia Psarra & George Kokotos. (2017) Autotaxin inhibitors: a patent review (2012-2016). Expert Opinion on Therapeutic Patents 27:7, pages 815-829.
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Edris Ebrahimi, Melinda Wuest, Jatinder Kaur, Atul Bhardwaj, Narendar Reddy Gade & Frank Wuest. (2023) [18F]ONO-8430506: A novel radioligand for PET imaging of autotaxin (ATX). Bioorganic & Medicinal Chemistry Letters 90, pages 129345.
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Jinxuan Ren, Jiaqi Lin, Lina Yu & Min Yan. (2022) Lysophosphatidylcholine: Potential Target for the Treatment of Chronic Pain. International Journal of Molecular Sciences 23:15, pages 8274.
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Jacqueline A. G. M. Langedijk, Ulrich H. Beuers & Ronald P. J. Oude Elferink. (2021) Cholestasis-Associated Pruritus and Its Pruritogens. Frontiers in Medicine 8.
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Souvik Banerjee, Derek D. Norman, Shanshan Deng, Sayo O. Fakayode, Sue Chin Lee, Abby L. Parrill, Wei Li, Duane D. Miller & Gabor J. Tigyi. (2020) Molecular modelling guided design, synthesis and QSAR analysis of new small molecule non-lipid autotaxin inhibitors. Bioorganic Chemistry 103, pages 104188.
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Christiana Magkrioti, Eleanna Kaffe, Elli-Anna Stylianaki, Camelia Sidahmet, Georgia Melagraki, Antreas Afantitis, Alexios N. Matralis & Vassilis Aidinis. (2020) Structure-Based Discovery of Novel Chemical Classes of Autotaxin Inhibitors. International Journal of Molecular Sciences 21:19, pages 7002.
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Eva Knuplez & Gunther Marsche. (2020) An Updated Review of Pro- and Anti-Inflammatory Properties of Plasma Lysophosphatidylcholines in the Vascular System. International Journal of Molecular Sciences 21:12, pages 4501.
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Yuzo Iwaki, Akira Ohhata, Shingo Nakatani, Katsuya Hisaichi, Yasuyuki Okabe, Atsushi Hiramatsu, Toshihide Watanabe, Shingo Yamamoto, Taihei Nishiyama, Juta Kobayashi, Yasuo Hirooka, Hideki Moriguchi, Tatsuo Maeda, Makoto Katoh, Yuka Komichi, Hiroto Ota, Naoya Matsumura, Masahiro Okada, Tetsuya Sugiyama, Hiroshi Saga & Akira Imagawa. (2020) ONO-8430506: A Novel Autotaxin Inhibitor That Enhances the Antitumor Effect of Paclitaxel in a Breast Cancer Model. ACS Medicinal Chemistry Letters 11:6, pages 1335-1341.
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N. Desroy & B. Heckmann. 2020. Anti-fibrotic Drug Discovery. Anti-fibrotic Drug Discovery 117 144 .
Nan Jiang, Yuhong Zhou, Minglin Zhu, Junlong Zhang, Meng Cao, Hongrui Lei, Ming Guo, Ping Gong, Guangyue Su & Xin Zhai. (2020) Optimization and evaluation of novel tetrahydropyrido[4,3-d]pyrimidine derivatives as ATX inhibitors for cardiac and hepatic fibrosis. European Journal of Medicinal Chemistry 187, pages 111904.
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Dimitrios Triantafyllos Gerokonstantis, Aikaterini Nikolaou, Christiana Magkrioti, Antreas Afantitis, Vassilis Aidinis, George Kokotos & Panagiota Moutevelis-Minakakis. (2020) Synthesis of novel 2-pyrrolidinone and pyrrolidine derivatives and study of their inhibitory activity against autotaxin enzyme. Bioorganic & Medicinal Chemistry 28:2, pages 115216.
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Kraljić, Jelić, Žiher, Cvrtila, Dragojević, Sinković & Mesić. (2019) Benzoxaboroles—Novel Autotaxin Inhibitors. Molecules 24:19, pages 3419.
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Myeong Hwi Lee, Dae-Yon Lee, Anand Balupuri, Jong-Woo Jeong & Nam Sook Kang. (2019) Pharmacophoric Site Identification and Inhibitor Design for Autotaxin. Molecules 24:15, pages 2808.
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Alexios N. Matralis, Antreas Afantitis & Vassilis Aidinis. (2018) Development and therapeutic potential of autotaxin small molecule inhibitors: From bench to advanced clinical trials. Medicinal Research Reviews 39:3, pages 976-1013.
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Patrick Mathieu & Marie-Chloé Boulanger. (2019) Autotaxin and Lipoprotein Metabolism in Calcific Aortic Valve Disease. Frontiers in Cardiovascular Medicine 6.
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Jingchuan Xue, Yunjia Lai, Liang Chi, Pengcheng Tu, Jiapeng Leng, Chih-Wei Liu, Hongyu Ru & Kun Lu. (2019) Serum Metabolomics Reveals That Gut Microbiome Perturbation Mediates Metabolic Disruption Induced by Arsenic Exposure in Mice. Journal of Proteome Research 18:3, pages 1006-1018.
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Ioanna Ninou, Eleanna Kaffe, Stefan Müller, David C. Budd, Christopher S. Stevenson, Christoph Ullmer & Vassilis Aidinis. (2018) Pharmacologic targeting of the ATX/LPA axis attenuates bleomycin-induced pulmonary fibrosis. Pulmonary Pharmacology & Therapeutics 52, pages 32-40.
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Kaede Takahashi, Kaori Fukushima, Kosuke Tanaka, Kanako Minami, Kaichi Ishimoto, Shiho Otagaki, Nobuyuki Fukushima, Kanya Honoki & Toshifumi Tsujiuchi. (2018) Involvement of LPA signaling via LPA receptor-2 in the promotion of malignant properties in osteosarcoma cells. Experimental Cell Research 369:2, pages 316-324.
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Ioanna Ninou, Christiana Magkrioti & Vassilis Aidinis. (2018) Autotaxin in Pathophysiology and Pulmonary Fibrosis. Frontiers in Medicine 5.
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Tongfei Jing, Xiuqi Miao, Feng Jiang, Ming Guo, Lingyun Xing, Junlong Zhang, Daiying Zuo, Hongrui Lei & Xin Zhai. (2018) Discovery and optimization of tetrahydropyrido[4,3-d]pyrimidine derivatives as novel ATX and EGFR dual inhibitors. Bioorganic & Medicinal Chemistry 26:8, pages 1784-1796.
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Aikaterini Nikolaou, Ioanna Ninou, Maroula G. Kokotou, Eleanna Kaffe, Antreas Afantitis, Vassilis Aidinis & George Kokotos. (2018) Hydroxamic Acids Constitute a Novel Class of Autotaxin Inhibitors that Exhibit in Vivo Efficacy in a Pulmonary Fibrosis Model . Journal of Medicinal Chemistry 61:8, pages 3697-3711.
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Anand Balupuri, Myeong Hwi Lee, Sangeun Chae, Eunmi Jung, Woosub Yoon, Yunki Kim, So Jung Son, Jeonghee Ryu, Dae-Hyuck Kang, Young-Jae Yang, Ji-Na You, Hyunjin Kwon, Jong-Woo Jeong, Tae-Sung Koo, Dae-Yon Lee & Nam Sook Kang. (2018) Discovery and optimization of ATX inhibitors via modeling, synthesis and biological evaluation. European Journal of Medicinal Chemistry 148, pages 397-409.
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Kyung-Hee Kim, Jungnam Joo, Boram Park, Sang-Jae Park, Woo Jin Lee, Sung-Sik Han, Tae Hyun Kim, Eun Kyung Hong, Sang Myung Woo & Byong Chul Yoo. (2017) Reduced levels of N’-methyl-2-pyridone-5-carboxamide and lysophosphatidylcholine 16:0 in the serum of patients with intrahepatic cholangiocarcinoma, and the correlation with recurrence-free survival. Oncotarget 8:68, pages 112598-112609.
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Christian A. Kuttruff, Marco Ferrara, Tom Bretschneider, Stefan Hoerer, Sandra Handschuh, Bernd Nosse, Helmut Romig, Paul Nicklin & Gerald J. Roth. (2017) Discovery of BI-2545: A Novel Autotaxin Inhibitor That Significantly Reduces LPA Levels in Vivo. ACS Medicinal Chemistry Letters 8:12, pages 1252-1257.
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Agnès Joncour, Nicolas Desroy, Christopher Housseman, Xavier Bock, Natacha Bienvenu, Laëtitia Cherel, Virginie Labeguere, Christophe Peixoto, Denis Annoot, Luce Lepissier, Jörg Heiermann, Willem Jan Hengeveld, Gregor Pilzak, Alain Monjardet, Emanuelle Wakselman, Veronique Roncoroni, Sandrine Le Tallec, René Galien, Christelle David, Nele Vandervoort, Thierry Christophe, Katja Conrath, Mia Jans, Alexandre Wohlkonig, Sameh Soror, Jan Steyaert, Robert Touitou, Damien Fleury, Lionel Vercheval, Patrick Mollat, Nicolas Triballeau, Ellen van der Aar, Reginald Brys & Bertrand Heckmann. (2017) Discovery, Structure–Activity Relationship, and Binding Mode of an Imidazo[1,2- a ]pyridine Series of Autotaxin Inhibitors . Journal of Medicinal Chemistry 60:17, pages 7371-7392.
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Kaede Takahashi, Kaori Fukushima, Nobuyuki Fukushima, Kanya Honoki & Toshifumi Tsujiuchi. (2017) Enhanced cellular functions through induction of LPA2 by cisplatin in fibrosarcoma HT1080 cells. Molecular and Cellular Biochemistry 431:1-2, pages 29-35.
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Nicolas Desroy, Christopher Housseman, Xavier Bock, Agnès Joncour, Natacha Bienvenu, Laëtitia Cherel, Virginie Labeguere, Emilie Rondet, Christophe Peixoto, Jean-Marie Grassot, Olivier Picolet, Denis Annoot, Nicolas Triballeau, Alain Monjardet, Emanuelle Wakselman, Veronique Roncoroni, Sandrine Le Tallec, Roland Blanque, Celine Cottereaux, Nele Vandervoort, Thierry Christophe, Patrick Mollat, Marieke Lamers, Marielle Auberval, Boska Hrvacic, Jovica Ralic, Line Oste, Ellen van der Aar, Reginald Brys & Bertrand Heckmann. (2017) Discovery of 2-[[2-Ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1-yl]-8-methylimidazo[1,2- a ]pyridin-3-yl]methylamino]-4-(4-fluorophenyl)thiazole-5-carbonitrile (GLPG1690), a First-in-Class Autotaxin Inhibitor Undergoing Clinical Evaluation for the Treatment of Idiopathic Pulmonary Fibrosis . Journal of Medicinal Chemistry 60:9, pages 3580-3590.
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Michelle J. Farquhar, Isla S. Humphreys, Simon A. Rudge, Garrick K. Wilson, Bishnupriya Bhattacharya, Maria Ciaccia, Ke Hu, Qifeng Zhang, Laurent Mailly, Gary M. Reynolds, Margaret Ashcroft, Peter Balfe, Thomas F. Baumert, Stephanie Roessler, Michael J.O. Wakelam & Jane A. McKeating. (2017) Autotaxin-lysophosphatidic acid receptor signalling regulates hepatitis C virus replication. Journal of Hepatology 66:5, pages 919-929.
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Souvik Banerjee, Derek D. Norman, Sue Chin Lee, Abby L. Parrill, Truc Chi T. Pham, Daniel L. Baker, Gabor J. Tigyi & Duane D. Miller. (2017) Highly Potent Non-Carboxylic Acid Autotaxin Inhibitors Reduce Melanoma Metastasis and Chemotherapeutic Resistance of Breast Cancer Stem Cells. Journal of Medicinal Chemistry 60:4, pages 1309-1324.
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Tian-Shu Kang, Wanhe Wang, Hai-Jing Zhong, Jia-Xin Liang, Chung-Nga Ko, Jin-Jian Lu, Xiu-Ping Chen, Dik-Lung Ma & Chung-Hang Leung. (2017) A rhodium(III)-based inhibitor of autotaxin with antiproliferative activity. Biochimica et Biophysica Acta (BBA) - General Subjects 1861:2, pages 256-263.
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Miku Hirane, Shuhei Ishii, Ayaka Tomimatsu, Kaori Fukushima, Kaede Takahashi, Nobuyuki Fukushima, Kanya Honoki & Toshifumi Tsujiuchi. (2016) Different induction of LPA receptors by chemical liver carcinogens regulates cellular functions of liver epithelial WB-F344 cells. Molecular Carcinogenesis 55:11, pages 1573-1583.
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Vinod S Hegade, Ruth Bolier, Ronald PJ Oude Elferink, Ulrich Beuers, Stuart Kendrick & David EJ Jones. (2016) A systematic approach to the management of cholestatic pruritus in primary biliary cirrhosis. Frontline Gastroenterology 7:3, pages 158-166.
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Diana CastagnaDavid C. BuddSimon J. F. MacdonaldCraig JamiesonAllan J. B. Watson. (2016) Development of Autotaxin Inhibitors: An Overview of the Patent and Primary Literature. Journal of Medicinal Chemistry 59:12, pages 5604-5621.
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Sadaharu Tabuchi. (2015) The autotaxin-lysophosphatidic acid–lysophosphatidic acid receptor cascade: proposal of a novel potential therapeutic target for treating glioblastoma multiforme. Lipids in Health and Disease 14:1.
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Shiori Mori, Mutsumi Araki, Shuhei Ishii, Miku Hirane, Kaori Fukushima, Ayaka Tomimatsu, Kaede Takahashi, Nobuyuki Fukushima & Toshifumi Tsujiuchi. (2015) LPA signaling through LPA receptors regulates cellular functions of endothelial cells treated with anticancer drugs. Molecular and Cellular Biochemistry 408:1-2, pages 147-154.
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Julia M. Broström, Zhi-wei Ye, Anna Axmon, Margareta Littorin, Håkan Tinnerberg, Christian H. Lindh, Huiyuan Zheng, Aram Ghalali, Ulla Stenius, Bo A.G. Jönsson & Johan Högberg. (2015) Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms. Toxicology and Applied Pharmacology 287:3, pages 222-231.
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Matthew G K Benesch, Yi M Ko, Xiaoyun Tang, Jay Dewald, Ana Lopez-Campistrous, Yuan Y Zhao, Raymond Lai, Jonathan M Curtis, David N Brindley & Todd P W McMullen. (2015) Autotaxin is an inflammatory mediator and therapeutic target in thyroid cancer. Endocrine-Related Cancer 22:4, pages 593-607.
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Efrosini Barbayianni, Eleanna Kaffe, Vassilis Aidinis & George Kokotos. (2015) Autotaxin, a secreted lysophospholipase D, as a promising therapeutic target in chronic inflammation and cancer. Progress in Lipid Research 58, pages 76-96.
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Matthew G.K. Benesch, Yi M. Ko, Todd P.W. McMullen & David N. Brindley. (2014) Autotaxin in the crosshairs: Taking aim at cancer and other inflammatory conditions. FEBS Letters 588:16, pages 2712-2727.
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Sarah A. Scott, Thomas P. Mathews, Pavlina T. Ivanova, Craig W. Lindsley & H. Alex Brown. (2014) Chemical modulation of glycerolipid signaling and metabolic pathways. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1841:8, pages 1060-1084.
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Anastassis Perrakis & Wouter H. Moolenaar. (2014) Autotaxin: structure-function and signaling. Journal of Lipid Research 55:6, pages 1010-1018.
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Matthew G. K. Benesch, Xiaoyun Tang, Tatsuo Maeda, Akira Ohhata, Yuan Y. Zhao, Bernard P. C. Kok, Jay Dewald, Mary Hitt, Jonathan M. Curtis, Todd P. W. McMullen & David N. Brindley. (2014) Inhibition of autotaxin delays breast tumor growth and lung metastasis in mice. The FASEB Journal 28:6, pages 2655-2666.
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Izabela Wocławek-Potocka, Paulina Rawińska, Ilona Kowalczyk-Zieba, Dorota Boruszewska, Emilia Sinderewicz, Tomasz Waśniewski & Dariusz Jan Skarzynski. (2014) Lysophosphatidic Acid (LPA) Signaling in Human and Ruminant Reproductive Tract. Mediators of Inflammation 2014, pages 1-14.
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Christiana Magkrioti. (2013) Autotaxin and lysophosphatidic acid signalling in lung pathophysiology. World Journal of Respirology 3:3, pages 77.
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