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Chemistry, Medicinal
Toshiya Ito, Kazutomo Kinoshita, Masaki Tomizawa, Shojiro Shinohara, Hiroki Nishii, Masayuki Matsushita, Kazuo Hattori, Yasunori Kohchi, Masami Kohchi, Tadakatsu Hayase, Fumio Watanabe, Kiyoshi Hasegawa, Hiroshi Tanaka, Shino Kuramoto, Kenji Takanashi, Nobuhiro Oikawa
Summary: In this study, chemical modification was employed to improve TRK inhibition and a potent inhibitor was identified.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Hongchao Zheng, Jichen Zhao, Bing Li, Weihe Zhang, Michael A. Stashko, Katherine A. Minson, Madeline G. Huey, Yubai Zhou, Henry Shelton Earp, Dmitri Kireev, Douglas K. Graham, Deborah DeRyckere, Stephen Frye, Xiaodong Wang
Summary: Inhibition of MER receptor tyrosine kinase (MERTK) contributes to tumor cell killing and stimulation of the immune response. UNC5293 is a highly selective MERTK inhibitor with potent and selective inhibition in cell-based assays, excellent mouse PK properties, and activity in leukemia cells in a murine model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Changwei Chen, Xin Chai, Xueping Hu, Shengying Lou, Dan Li, Tingjun Hou, Sunliang Cui
Summary: A new core structure for androgen receptor antagonists was designed and synthesized, which showed antiandrogen resistance activity at a non-traditional targeting site and effectively inhibited tumor growth in an animal study. This study provides new possibilities for the development of prostate cancer therapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Chengbin Yang, Yi Chen, Tianze Wu, Yunjian Gao, Xiaofeng Liu, Yongtai Yang, Yun Ling, Yu Jia, Mingli Deng, Jianxin Wang, Yaming Zhou
Summary: The PI3K-Akt-mTOR pathway is highly activated in human hematological malignancies and has shown promise as a potential target for acute myeloid leukemia (AML) therapy. In this study, we synthesized a series of 7-azaindazole derivatives as potent dual inhibitors of PI3K/mTOR, with compound FD274 showing excellent inhibitory activity. In vitro and in vivo studies demonstrated the potential of FD274 as a targeted anti-AML drug candidate.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Benjamin R. Bellenie, Edward Hall, Ian Bruce, Matthew Spendiff, Andrew Culshaw, Sarah McDonald, Ameet Ambarkhane, Colin Chinn, Matthew Thomas, Elisabeth Rosner, Marguerite Bracher, Paul Nicklin, Stephen Marshall, Julie Coote, Eva Cullen, Clemence Tessier, Kuno Wuersch, Ajay Lal, Gillian Wallis, Gregory J. Hollingworth, James Neef
Summary: A new physiologically relevant in vitro human whole blood neutrophil assay was used to identify and prioritize a series of selective PI3K inhibitors. Compound 33 showed good efficacy in vivo studies but encountered unexpected inflammatory cell infiltrates in cardiovascular tissue during toxicological studies, preventing further compound development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Wataru Kawahata, Tokiko Asami, Takao Kiyoi, Takayuki Irie, Shigeki Kashimoto, Hatsuo Furuichi, Masaaki Sawa
Summary: The study identified a series of novel noncovalent BTK inhibitors, among which 13f (AS-1763) as a next-generation noncovalent BTK inhibitor, showed good oral availability, potency, and selectivity, with significant efficacy in in vivo tumor xenograft models, and has advanced to phase 1 clinical trials.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yuhei Horai, Naoki Suda, Shinsuke Uchihashi, Mayako Katakuse, Tomomi Shigeno, Takashige Hirano, Junichi Takahara, Tomoyuki Fujita, Yohei Mukoyama, Yuji Haga
Summary: The discovery of a novel BRD4 inhibitor for melanoma therapy is outlined in this study. Through modifications of existing molecules and the introduction of new structures, a compound with potent inhibitory activity and favorable pharmacokinetic properties was successfully developed. This compound demonstrated significant antitumor efficacy in a mouse melanoma model, indicating its potential as a therapeutic agent for melanoma treatment.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Xishan Wu, Hui Shen, Yan Zhang, Chao Wang, Qiu Li, Cheng Zhang, Xiaoxi Zhuang, Chenchang Li, Yudan Shi, Yanli Xing, Qiuping Xiang, Jinxin Xu, Donghai Wu, Jinsong Liu, Yong Xu
Summary: The study reports a novel inverse agonist as a therapeutic target for ROR gamma, showing potent inhibition activity and selectivity, as well as good suppression in prostate cancer cell lines, along with good pharmacokinetic properties.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Pengxing He, Jing Jing, Linna Du, Xuyang Zhang, Yufei Ren, Han Yang, Bin Yu, Hongmin Liu
Summary: YS-363 is a novel EGFR inhibitor that demonstrates potent reversible inhibition and excellent activities against cell proliferation, migration, cell cycle and apoptosis. It is a promising selective inhibitor that can potentially be developed as a more effective anti-lung cancer agent targeting EGFR.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Chemistry, Medicinal
Shingpan Chan, Yunong Zhang, Jie Wang, Qiuchun Yu, Xia Peng, Jian Zou, Licheng Zhou, Li Tan, Yunxin Duan, Yang Zhou, Hoon Hur, Jing Ai, Zhen Wang, Xiaomei Ren, Zhang Zhang, Ke Ding
Summary: The study describes the discovery of 3-aminopyrazole derivatives as potent and selective AXL kinase inhibitors. One representative compound, 6li, showed strong inhibitory activity against AXL enzymatic activity and demonstrated significant antitumor efficacy in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Lukas Waterloo, Harald Huebner, Fabrizio Fierro, Tara Pfeiffer, Regine Brox, Stefan Loeber, Dorothee Weikert, Masha Y. Niv, Peter Gmeiner
Summary: TAS2R14 is a bitter taste receptor found in multiple locations, including the tongue and human airway smooth muscle. Activation of TAS2R14 can lead to bronchodilation, making it a potential target for treating asthma or chronic obstructive pulmonary disease. By modifying the structure of flufenamic acid, a study identified a group of effective and potent TAS2R14 agonists called 2-aminopyridines with a tetrazole unit. The most potent ligand, 28.1, showed a six-fold higher potency than flufenamic acid and demonstrated selectivity over other human taste receptors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Tingting Jin, Lei Xu, Peipei Wang, Xiaobei Hu, Runyuan Zhang, Zhiqi Wu, Wenxin Du, Weijuan Kan, Kun Li, Chang Wang, Yubo Zhou, Jia Li, Tao Liu
Summary: In this study, a strategy involving trifluoromethyl substitution was used to develop an orally bioavailable CHK1 inhibitor, compound 6c, which exhibited higher plasma exposure and good kinase selectivity in mice. Compound 6c demonstrated significant antiproliferative effects in various cell lines and inhibited tumor growth in mouse models. Additionally, it showed a synergistic effect when combined with gemcitabine in certain xenograft mouse models.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Hefeng Zhang, Xia Peng, Yang Dai, Jingwei Shao, Yinchun Ji, Yiming Sun, Bo Liu, Xu Cheng, Jing Ai, Wenhu Duan
Summary: Compound 13c is a highly potent and orally bioavailable Axl inhibitor, showing inhibition of both Axl superfamily kinases and the oncogenic kinase Met. It exhibits significant antitumor efficacy in Axl-driven and Met-driven tumor models, making it a promising therapeutic candidate for cancer treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Lukas Waterloo, Harald Hubner, Fabrizio Fierro, Tara Pfeiffer, Regine Brox, Stefan Loeber, Dorothee Weikert, Masha Y. Niv, Peter Gmeiner
Summary: The TAS2R14 receptor, found in the tongue, human airway smooth muscle, and other tissues, is a potential target for asthma and chronic obstructive pulmonary disease treatment. By modifying the structure of flufenamic acid, we developed a set of promising TAS2R14 agonists, particularly ligand 28.1, which showed higher potency and selectivity compared to flufenamic acid and other taste receptors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Martin A. . Lowe, Alvaro Cardenas, Jean-Pierre Valentin, Zhaoning Zhu, Jan Abendroth, Jose L. Castro, Reiner Class, Annie Delaunois, Renaud Fleurance, Helga Gerets, Vitalina Gryshkova, Lloyd King, Donald D. Lorimer, Malcolm MacCoss, Julian H. Rowley, Marie-Luce Rosseels, Leandro Royer, Richard D. Taylor, Melanie Wong, Oliver Zaccheo, Vishal P. Chavan, Gokul A. . Ghule, Bapusaheb K. Tapkir, Jeremy N. Burrows, Maelle Duffey, Matthias Rottmann, Sergio Wittlin, Inigo Angulo-Barturen, Maria Belen Jimenez-Diaz, Josefine Striepen, Kate J. Fairhurst, Tomas Yeo, David A. . Fidock, Alan F. Cowman, Paola Favuzza, Benigno Crespo-Fernandez, Francisco Javier Gamo, Daniel E. Goldberg, Dominique Soldati-Favre, Benoit Laleu, Teresa de Haro
Summary: This study optimized Plasmepsin X (PMX) and identified potent PMX inhibitors with potential efficacy in treating malaria.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
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Chemistry, Medicinal
Lewis Gazzard, Karen Williams, Huifen Chen, Lorraine Axford, Elizabeth Blackwood, Brenda Burton, Kerry Chapman, Peter Crackett, Joy Drobnick, Charles Ellwood, Jennifer Epler, Michael Flagella, Emanuela Gancia, Matthew Gill, Simon Goodacre, Jason Halladay, Joanne Hewitt, Hazel Hunt, Samuel Kintz, Joseph Lyssikatos, Calum Macleod, Sarah Major, Guillaume Medard, Raman Narukulla, Judi Ramiscal, Stephen Schmidt, Eileen Seward, Christian Wiesmann, Ping Wu, Sharon Yee, Ivana Yen, Shiva Malek
JOURNAL OF MEDICINAL CHEMISTRY
(2015)
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Multidisciplinary Sciences
Anita Schlierf, Eva Altmann, Jean Quancard, Anne B. Jefferson, Rene Assenberg, Martin Renatus, Matthew Jones, Ulrich Hassiepen, Michael Schaefer, Michael Kiffe, Andreas Weiss, Christian Wiesmann, Richard Sedrani, Jorg Eder, Bruno Martoglio
NATURE COMMUNICATIONS
(2016)
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Chemistry, Medicinal
Kenji Namoto, Finton Sirockin, Holger Sellner, Christian Wiesmann, Frederic Villard, Robert J. Moreau, Eric Valeur, Stephanie C. Paulding, Simone Schleeger, Kathrin Schipp, Joachim Loup, Lori Andrews, Ryann Swale, Michael Robinson, Christopher J. Farady
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Review
Biotechnology & Applied Microbiology
Jean-Paul Renaud, Ashwin Chari, Claudio Ciferri, Wen-ti Liu, Herve-William Remigy, Holger Stark, Christian Wiesmann
NATURE REVIEWS DRUG DISCOVERY
(2018)
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Chemistry, Medicinal
Steven T. Staben, Nicole Blaquiere, Vickie Tsui, Aleksandr Kolesnikov, Steven Do, Erin K. Bradley, Jenna Dotson, Richard Goldsmith, Timothy P. Heffron, John Lesnick, Cristina Lewis, Jeremy Murray, Jim Nonomiya, Alan G. Olivero, Jodie Pang, Lionel Rouge, Laurent Salphati, BinQing Wei, Christian Wiesmann, Ping Wu
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2013)
Article
Chemistry, Medicinal
Kirk D. Robarge, Wendy Lee, Charles Eigenbrot, Mark Ultsch, Christian Wiesmann, Robert Heald, Steve Price, Joanne Hewitt, Philip Jackson, Pascal Savy, Brenda Burton, Edna F. Choo, Jodie Pang, Jason Boggs, April Yang, Xioaye Yang, Matthew Baumgardner
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2014)
Article
Chemistry, Medicinal
Lewis Gazzard, Brent Appleton, Kerry Chapman, Huifen Chen, Kevin Clark, Joy Drobnick, Simon Goodacre, Jason Halladay, Joseph Lyssikatos, Stephen Schmidt, Steve Sideris, Christian Wiesmann, Karen Williams, Ping Wu, Ivana Yen, Shiva Malek
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2014)
Article
Biochemistry & Molecular Biology
Xiaolei Ma, Pierre A. Barthelemy, Lionel Rouge, Christian Wiesmann, Sachdev S. Sidhu
JOURNAL OF MOLECULAR BIOLOGY
(2013)
Article
Biochemistry & Molecular Biology
Andreas Ernst, Brent A. Appleton, Ylva Ivarsson, Yingnan Zhang, David Gfeller, Christian Wiesmann, Sachdev S. Sidhu
JOURNAL OF MOLECULAR BIOLOGY
(2014)
Article
Multidisciplinary Sciences
Georgia Hatzivassiliou, Jacob R. Haling, Huifen Chen, Kyung Song, Steve Price, Robert Heald, Joanne F. M. Hewitt, Mark Zak, Ariana Peck, Christine Orr, Mark Merchant, Klaus P. Hoeflich, Jocelyn Chan, Shiuh-Ming Luoh, Daniel J. Anderson, Mary J. C. Ludlam, Christian Wiesmann, Mark Ultsch, Lori S. Friedman, Shiva Malek, Marcia Belvin
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Biotechnology & Applied Microbiology
Joerg Eder, Richard Sedrani, Christian Wiesmann
NATURE REVIEWS DRUG DISCOVERY
(2014)
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Multidisciplinary Sciences
Nikolaus Schiering, Allan D'Arcy, Frederic Villard, Paul Ramage, Claude Logel, Frederic Cumin, Gary M. Ksander, Christian Wiesmann, Rajeshri G. Karki, Muneto Mogi
SCIENTIFIC REPORTS
(2016)
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Immunology
John M. Lindner, Vanessa Cornacchione, Atul Sathe, Celine Be, Honnappa Srinivas, Elodie Riquet, Xavier-Charles Leber, Andreas Hein, Matthias B. Wrobel, Meike Scharenberg, Thomas Pietzonka, Christian Wiesmann, Johanna Abend, Elisabetta Traggiai
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Multidisciplinary Sciences
Anna Schubart, Karen Anderson, Nello Mainolfi, Holger Sellner, Takeru Ehara, Christopher M. Adams, Aengus Mac Sweeney, Sha-Mei Liao, Maura Crowley, Amanda Littlewood-Evans, Sophie Sarret, Grazyna Wieczorek, Ludovic Perrot, Valerie Dubost, Thierry Flandre, Yuzhou Zhang, Richard J. H. Smith, Antonio M. Risitano, Rajeshri G. Karki, Chun Zhang, Eric Valeur, Finton Sirockin, Bernd Gerhartz, Paulus Erbel, Nicola Hughes, Thomas M. Smith, Frederic Cumin, Upendra A. Argikar, Boerje Haraldsson, Muneto Mogi, Richard Sedrani, Christian Wiesmann, Bruce Jaffee, Juergen Maibaum, Stefanie Flohr, Richard Harrison, Joerg Eder
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
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Biochemistry & Molecular Biology
Keith Jendza, Mitsunori Kato, Michael Salcius, Honnappa Srinivas, Andrea De Erkenez, Anh Nguyen, Doug McLaughlin, Celine Be, Christian Wiesmann, Jason Murphy, Philippe Bolduc, Muneto Mogi, Jose Duca, Abdel Namil, Michael Capparelli, Veronique Darsigny, Erik Meredith, Ritesh Tichkule, Luciana Ferrara, Jessica Heyder, Fang Liu, Patricia A. Horton, Michael J. Romanowski, Markus Schirle, Nello Mainolfi, Karen Anderson, Gregory A. Michaud
NATURE CHEMICAL BIOLOGY
(2019)