Article
Immunology
Anne Lesage, Francois Marceau, Christoph Gibson, Brigitte Loenders, Werner Katzer, Horst-Dieter Ambrosi, Jorn Saupe, Alexander Faussner, Evangelia Pardali, Jochen Knolle
Summary: PHA-022121 is a novel small molecule antagonist of the human bradykinin B-2 receptor that shows high affinity, high antagonist potency, and high selectivity, making it a potential treatment and prevention option for hereditary angioedema attacks.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Jonas Ghouse, Gustav Ahlberg, Laura Andreasen, Karina Banasi, Soren Brunak, Michael Schwinn, Ina Holst Larsen, Oscar Petersen, Erik Sorensen, Henrik Ullum, Eva Rye Rasmussen, Niclas Eriksson, Paer Hallberg, Mia Wadelius, Henning Bundgaard, Morten S. Olesen
Summary: A genetic locus at chromosome 14q32.2 was found to be associated with ACE inhibitor-related angioedema in individuals of European descent. Carriers of the risk allele had significantly lower blood pressure, suggesting a potential mechanism linking genetic variants near the bradykinin receptor B2 gene with angioedema risk.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Article
Neurosciences
Sergio R. Rodriguez-Masso, Michelle A. Erickson, William A. Banks, Henning Ulrich, Antonio Henrique Martins
Summary: Bradykinin is effective in disrupting BBB, but limited by its short half-life and undesirable biological activity. Further research with stable analogs like NG291 show promising results in increasing BBB permeability without significant neurotoxicity.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Guohui Yang, Pengfei Yao, Shengli Ma, Chi Zhang
Summary: In rats with spinal cord ischemic injury, levels of bradykinin and B2 receptors were decreased. Bradykinin treatment significantly improved motor function, reduced inflammatory mediators, and activated B2 receptors, suggesting a potential mechanism for improving hind limb recovery.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Chemistry, Medicinal
Renato Ferreira de Freitas, Yanli Liu, Magdalena M. Szewczyk, Naimee Mehta, Fengling Li, David McLeod, Carlos Zepeda-Velazquez, David Dilworth, Ronan P. Hanley, Elisa Gibson, Peter J. Brown, Rima Al-Awar, Lindsey James, Cheryl H. Arrowsmith, Dalia Barsyte-Lovejoy, Jinrong Min, Masoud Vedadi, Matthieu Schapira, Abdellah Allali-Hassani
Summary: This study identified the first antagonist that blocks the interaction between NSD2 and H3K36me2, providing a potential new approach for targeting NSD2 and further understanding its cellular function.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Oncology
Byung-Gyu Kim, Ehsan Malek, Sung Hee Choi, James J. Ignatz-Hoover, James J. Driscoll
Summary: The TGF-beta signaling pathway plays a crucial role in physiological cellular processes and is dysregulated in pathologies such as cancer. It can function as either a tumor promoter or a tumor suppressor, affecting processes such as cell proliferation, migration, invasion, metastasis, and immunosurveillance. Various therapeutic strategies targeting TGF-beta signaling have shown promise in preclinical studies and clinical trials, but challenges remain in balancing its tumor-promoting and tumor-suppressing activities for effective cancer treatment.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Chemistry, Medicinal
Sebastian Dekkers, Birgit Caspar, Joelle Goulding, Nicholas D. Kindon, Laura E. Kilpatrick, Leigh A. Stoddart, Stephen J. Briddon, Barrie Kellam, Stephen J. Hill, Michael J. Stocks
Summary: In this study, fluorescent probes based on previously reported small-molecule antagonists were designed and synthesized using classic medicinal chemistry approaches to investigate the pharmacology and cellular distribution of the CXCR4 receptor. Three distinct chemical classes of fluorescent probes were developed and shown to specifically bind to the CXCR4 receptor in a fluorescence-based NanoBRET binding assay (pKD ranging 6.6-7.1). These probes were also used in competition binding experiments and confocal microscopy to further explore the pharmacology and cellular distribution of CXCR4.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Helene Bachelard, Francois Marceau
Summary: Noscapine and raloxifene were claimed to be bradykinin B2 receptor antagonists, but our study showed that they do not possess this inhibitory effect. This suggests that previous reports might contain misleading information.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yiou Wang, Bingxue Zhang, Yibing Huang, Wenjun Yao, Fei Tao, Yuxin Chen
Summary: The novel BK receptor inhibitors J051-71 and J051-105 were found to reduce the viability of liver cancer cells and inhibit colony formation, possibly by inhibiting the ERK pathway. These inhibitors also reversed the cell proliferation induced by BK by downregulating B1 receptor expression, suggesting a potential target for HCC therapy.
Review
Chemistry, Medicinal
Francois Marceau, Helene Bachelard
Summary: Bradykinin (BK) plays various roles in the body, and the clinical applications of B2R antagonists are still under investigation. The classical smooth muscle contractility assay is crucial for studying drug potency. The use of the isolated human umbilical vein in experiments allows for verification of different types of drugs' effects on B2R.
Article
Urology & Nephrology
Jorge L. Gamboa, Cindy A. Mambungu, Adrienne R. Clagett, Hui Nian, Chang Yu, T. Alp Ikizler, Nancy J. Brown
Summary: Intradialytic hypotension is a common complication in patients undergoing maintenance hemodialysis and is associated with increased morbidity and mortality. This study examines the potential of using a bradykinin B-2 receptor blocker to prevent intradialytic hypotension.
Article
Endocrinology & Metabolism
Elizabeth K. M. Johnstone, Mohammed Akli Ayoub, Rebecca J. Hertzman, Heng B. See, Rekhati S. Abhayawardana, Ruth M. Seeber, Kevin D. G. Pfleger
Summary: This study investigated the heteromerization of AT(2) and B-2 receptors in HEK293FT cells. The results demonstrated the functional interaction between these receptors and the differences in signaling, providing important evidence for studying GPCR pharmacology and signaling diversity.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Pharmacology & Pharmacy
Xiaohong Cen, Baoqu Wang, Yuqing Liang, Yanlin Chen, Yu Xiao, Shaohua Du, Kutty Selva Nandakumar, Hang Yin, Shuwen Liu, Kui Cheng
Summary: This study revealed the clinical relevance of TLR3 upregulation in human atherosclerosis and its contribution to the disease processes. Inhibition of TLR3 led to reduced foam cell formation and atherosclerotic burden, suggesting TLR3 as a potential novel target for atherosclerosis therapy.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Biochemistry & Molecular Biology
Willem F. J. Karstens, Wiro M. B. P. Menge, Gijs Martens, Sanne J. N. Op Het Veld, Jacobus Th. H. van Eupen, Marco Demon, Tanja A. E. van Achterberg, Monica J. Arisse-Thijssen, Ellen W. H. Santegoeds-Lenssen, Miranda M. C. van der Lee, Ruud Ubink, Roel J. Arends, Aloys Sesink, Marion Blomenrohr, C. Marco Timmers
Summary: This paper describes the discovery of a novel small molecule TSH-R antagonist, SYD5115 (67), with nanomolar potency. SYD5115 also blocks the synthesis of thyroid hormone T4 induced by stimulating antibodies after a single oral dose. During optimization, issues such as low metabolic stability and potential mutagenicity of the initial compounds had to be addressed.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Endocrinology & Metabolism
George J. Kahaly, Lisa Steiner, Miranda M. C. van der Lee, Tanja A. E. van Achterberg, Roel J. Arends, Willem F. J. Karstens, Tobias Weirauch, Jil Henseling, Lara Frommer, Jan Wolf, Augustine George
Summary: The novel low-molecular-weight compound SYD5115 showed significant and dose-dependent inhibition of TSH-R activation induced by M22 or TSAb-positive sera in vitro. The inhibitory activity of SYD5115 was observed in CHO cells and primary human orbital fibroblasts, demonstrating its potential as a therapeutic agent for Graves' hyperthyroidism and Graves' orbitopathy.
Article
Rheumatology
Maria Juarez, Holger Bang, Friederike Hammar, Ulf Reimer, Bernard Dyke, Ilfita Sahbudin, Christopher D. Buckley, Benjamin Fisher, Andrew Filer, Karim Raza
ANNALS OF THE RHEUMATIC DISEASES
(2016)
Article
Immunology
Ludwig Schlemm, Rene Markus Giess, Ludwig Rasche, Catherina Pfuhl, Katharina Wakonig, Janina Ruth Behrens, Carmen Scheibenbogen, Judith Bellmann-Strobl, Friedemann Paul, Ulf Reimer, Klemens Ruprecht
JOURNAL OF NEUROIMMUNOLOGY
(2016)
Article
Biochemical Research Methods
Daniel P. Zolg, Mathias Wilhelm, Karsten Schnatbaum, Johannes Zerweck, Tobias Knaute, Bernard Delanghe, Derek J. Bailey, Siegfried Gessulat, Hans-Christian Ehrlich, Maximilian Weininger, Peng Yu, Judith Schlegl, Karl Kramer, Tobias Schmidt, Ulrike Kusebauch, Eric W. Deutsch, Ruedi Aebersold, Robert L. Moritz, Holger Wenschuh, Thomas Moehring, Stephan Aiche, Andreas Huhmer, Ulf Reimer, Bernhard Kuster
Article
Biochemical Research Methods
Daniel Paul Zolg, Mathias Wilhelm, Peng Yu, Tobias Knaute, Johannes Zerweck, Holger Wenschuh, Ulf Reimer, Karsten Schnatbaum, Bernhard Kuster
Article
Parasitology
P. Maksimov, W. Basso, J. Zerweck, M. Schutkowski, U. Reimer, A. Maksimov, F. J. Conraths, G. Schares
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2018)
Article
Biochemical Research Methods
Chien-Yun Lee, Dongxue Wang, Mathias Wilhelm, Daniel P. Zolg, Tobias Schmidt, Karsten Schnatbaum, Ulf Reimer, Fredrik Ponten, Mathias Uhlen, Hannes Hahne, Bernhard Kuster
MOLECULAR & CELLULAR PROTEOMICS
(2018)
Article
Biochemical Research Methods
Daniel Paul Zolg, Mathias Wilhelm, Tobias Schmidt, Guillaume Medard, Johannes Zerweck, Tobias Knaute, Holger Wenschuh, Ulf Reimer, Karsten Schnatbaum, Bernhard Kuster
MOLECULAR & CELLULAR PROTEOMICS
(2018)
Article
Multidisciplinary Sciences
Madlen Loebel, Maren Eckey, Franziska Sotzny, Elisabeth Hahn, Sandra Bauer, Patricia Grabowski, Johannes Zerweck, Pavlo Holenya, Leif G. Hanitsch, Kirsten Wittke, Peter Borchmann, Jens-Ulrich Rueffer, Falk Hiepe, Klemens Ruprecht, Uta Behrends, Carola Meindl, Hans-Dieter Volk, Ulf Reimer, Carmen Scheibenbogen
Article
Biochemical Research Methods
Siegfried Gessulat, Tobias Schmidt, Daniel Paul Zolg, Patroklos Samaras, Karsten Schnatbaum, Johannes Zerweck, Tobias Knaute, Julia Rechenberger, Bernard Delanghe, Andreas Huhmer, Ulf Reimer, Hans-Christian Ehrlich, Stephan Aiche, Bernhard Kuster, Mathias Wilhelm
Article
Immunology
Yuka Nadai, Kathrin Held, Sarah Joseph, Mohamed I. M. Ahmed, Verena S. Hoffmann, David Peterhoff, Marco Missange, Asli Bauer, Agricola Joachim, Ulf Reimer, Johannes Zerweck, Sheena McCormack, Alethea Cope, Roger Tatoud, Robin J. Shattock, Merlin Lee Robb, Eric G. Sandstroem, Michael Hoelscher, Leonard Maboko, Muhammad Bakari, Arne Kroidl, Ralf Wagner, Jonathan Weber, Georgios Pollakis, Christof Geldmacher
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Biochemical Research Methods
Karsten Schnatbaum, Victor Solis-Mezarino, Daniil Pokrovsky, Frederike Schaefer, Dennis Nagl, Lars Hornberger, Johannes Zerweck, Tobias Knaute, Julia Avramova-Nehmer, Mike Schutkowski, Veit Hornung, Holger Wenschuh, Moritz Carl Voelker-Albert, Axel Imhof, Ulf Reimer
Article
Multidisciplinary Sciences
Julian Braun, Lucie Loyal, Marco Frentsch, Daniel Wendisch, Philipp Georg, Florian Kurth, Stefan Hippenstiel, Manuela Dingeldey, Beate Kruse, Florent Fauchere, Emre Baysal, Maike Mangold, Larissa Henze, Roland Lauster, Marcus A. Mall, Kirsten Beyer, Jobst Roehmel, Sebastian Voigt, Juergen Schmitz, Stefan Miltenyi, Ilja Demuth, Marcel A. Mueller, Andreas Hocke, Martin Witzenrath, Norbert Suttorp, Florian Kern, Ulf Reimer, Holger Wenschuh, Christian Drosten, Victor M. Corman, Claudia Giesecke-Thiel, Leif Erik Sander, Andreas Thiel
Article
Multidisciplinary Sciences
Oliver Klein, Akvile Haeckel, Ulf Reimer, Grit Nebrich, Eyk Schellenberger
SCIENTIFIC REPORTS
(2020)
Article
Multidisciplinary Sciences
Lucie Loyal, Julian Braun, Larissa Henze, Beate Kruse, Manuela Dingeldey, Ulf Reimer, Florian Kern, Tatjana Schwarz, Maike Mangold, Clara Unger, Friederike Dorfler, Shirin Kadler, Jennifer Rosowski, Kubrah Gurcan, Zehra Uyar-Aydin, Marco Frentsch, Florian Kurth, Karsten Schnatbaum, Maren Eckey, Stefan Hippenstiel, Andreas Hocke, Marcel A. Muller, Birgit Sawitzki, Stefan Miltenyi, Friedemann Paul, Marcus A. Mall, Holger Wenschuh, Sebastian Voigt, Christian Drosten, Roland Lauster, Nils Lachman, Leif-Erik Sander, Victor M. Corman, Jobst Rohmel, Lil Meyer-Arndt, Andreas Thiel, Claudia Giesecke-Thiel
Summary: The study demonstrates that preexisting spike-cross-reactive T cells play a functional role in the immune response to SARS-CoV-2 infection and vaccination. Cross-reactive immunity may explain the rapid induction of immunity after primary SARS-CoV-2 immunization and the high rate of asymptomatic or mild COVID-19 cases.
Article
Multidisciplinary Sciences
Gunnar Dittmar, Daniel Perez Hernandez, Elisabeth Kowenz-Leutz, Marieluise Kirchner, Gunther Kahlert, Radoslaw Wesolowski, Katharina Baum, Maria Knoblich, Maria Hofstaetter, Arnaud Muller, Jana Wolf, Ulf Reimer, Achim Leutz