Article
Pharmacology & Pharmacy
Huamei Forsman, Yanling Wu, Jonas Martensson, Lena Bjorkman, Kenneth L. Granberg, Claes Dahlgren, Martina Sundqvist
Summary: Formyl peptide receptor 1 (FPR1) is a G protein-coupled receptor that recognizes short N-formylated peptides. The recently discovered FPR1 antagonist AZ2158 is a potent inhibitor of neutrophil chemotaxis and can act on both balanced and biased FPR1 agonists. This compound shows promise for further study of FPR1-mediated activities.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tiziana Pecchillo Cimmino, Ester Pagano, Mariano Stornaiuolo, Gabriella Esposito, Rosario Ammendola, Fabio Cattaneo
Summary: Glucose and glutamine are important for the metabolic reprogramming of cancer cells. FPR2, a membrane receptor, plays a role in regulating multiple metabolic pathways in cancer cells.
Review
Biochemistry & Molecular Biology
Jie Fang, Rui Sheng, Zheng-Hong Qin
Summary: This review highlights the role of Nox-derived ROS in regulating various signals in the central nervous system, with different Nox homologues leading to different signaling cascades. The varied roles of NOX enzyme homologues in different signaling pathways and conditions underscore the need for selective Nox inhibitors in treating CNS diseases.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Multidisciplinary Sciences
Woon Yong Kwon, Gil Joon Suh, Yoon Sun Jung, Seung Min Park, Subi Oh, Sung Hee Kim, A. Rum Lee, Jeong Yeon Kim, Hayoung Kim, Kyung Ah Kim, Young Kim, Byoung Choul Kim, Taegyun Kim, Kyung Su Kim, Kiyoshi Itagaki, Carl J. Hauser
Summary: The study revealed a strong association between circulating ND6 levels in patients with septic shock and the development of secondary infection, as well as increased mortality rates. Suppression of PMN chemotaxis may play a key role in the increased susceptibility to secondary infection in these patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Tiziana Pecchillo Cimmino, Ester Pagano, Mariano Stornaiuolo, Gabriella Esposito, Rosario Ammendola, Fabio Cattaneo
Summary: Stimulation of FPR2 activates metabolic pathways in cancer cells, including glucose metabolism and lactate production. This study suggests that targeting FPR2 signaling could be a new therapeutic approach for cancer treatment.
Review
Biology
Valentina Maria Caso, Valentina Manzo, Tiziana Pecchillo Cimmino, Valeria Conti, Pio Caso, Gabriella Esposito, Vincenzo Russo, Amelia Filippelli, Rosario Ammendola, Fabio Cattaneo
Summary: This article explores the important role of Formyl-Peptide Receptors (FPRs) in cardiovascular pathologies and their regulation of oxidative stress. Different members of the FPR family modulate NADPH oxidase through various mechanisms and trigger cellular signaling. Furthermore, some FPR agonists may induce inflammatory responses while others activate anti-inflammatory pathways.
Article
Cell Biology
Simon Lind, Claes Dahlgren, Rikard Holmdahl, Peter Olofsson, Huamei Forsman
Summary: The study reveals that RE-04-001 specifically targets and activates FPR1 at very low concentrations, leading to biased signaling towards the PLC-PIP2-Ca(2+) pathway and ERK1/2 activation while avoiding beta-arrestin recruitment. Compared to the peptide agonist fMLF, RE-04-001 displays a more resistant response and a functional selective effect on human neutrophils, making it a potential tool for further studies and drug development targeting FPR1.
JOURNAL OF LEUKOCYTE BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Geng Chen, Xiankun Wang, Qiwen Liao, Yunjun Ge, Haizhan Jiao, Qiang Chen, Yezhou Liu, Wenping Lyu, Lizhe Zhu, Gydo C. P. van Zundert, Michael J. Robertson, Georgios Skiniotis, Yang Du, Hongli Hu, Richard D. Ye
Summary: The formyl peptide receptor 1 (FPR1) plays a critical role in detecting short peptides characteristic of protein synthesis in bacteria and mitochondria, and is important in phagocyte migration and activation during bacterial infection, tissue injury and inflammation. This study reveals the structural basis of FPR1 recognition of bacteria-derived chemotactic peptides, providing insights for developing FPR1-targeting agents.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Stephenson B. Owusu, Elodie Hudik, Celine Ferard, Sophie Dupre-Crochet, Eric C. D. K. Addison, Kwasi Preko, Tania Bizouarn, Chantal Houee-Levin, Laura Baciou
Summary: Simulating oxidative stress with gamma irradiation leads to shortened half-lives of neutrophils but pre-activates surviving cells to produce superoxide anions. Incomplete assembly of the NADPH oxidase complex after irradiation significantly enhances neutrophil reactivity.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Irina Tikhonova, Alsu Dyukina, Elvira Shaykhutdinova, Valentina Safronova
Summary: The signaling of membrane receptors is modified in obesity characterized by low-grade inflammation. The obesity-resistant state of organisms is poorly understood. We analyzed the generation of reactive oxygen species (ROS) initiated though membrane formyl peptide receptors (Fpr1, Fpr2) in bone-marrow granulocytes of obesity-resistant mice (ORM).
Article
Biochemistry & Molecular Biology
Hannah Mason, Ganesha Rai, Arina Kozyr, Nathaniel De Jonge, Emily Gliniewicz, Lars J. Berg, Gal Wald, Cayce Dorrier, Mark J. Henderson, Alexey Zakharov, Tristan Dyson, John Audley, Anthony M. Pettinato, Elias Carvalho Padilha, Pranav Shah, Xin Xu, Thomas L. Leto, Anton Simeonov, Kol A. Zarember, Dorian B. McGavern, John I. Gallin
Summary: NADPH oxidases (NOX's) and the reactive oxygen species (ROS) they produce are involved in various physiological processes, but excessive ROS production is associated with several diseases. In this study, a small molecule inhibitor, NCATS-SM7270, was developed and shown to specifically inhibit NOX2 activity in human and mouse granulocytes. The role of different NOX isoforms in mild traumatic brain injury (mTBI) was investigated, and it was found that NOX2 deficiency provided protection against mTBI pathology, while NOX4 deficiency exacerbated the injury. Treatment of mice with NCATS-SM7270 after mTBI reduced cortical cell death in a dose-dependent manner, and also partially reversed cortical damage in NOX4-deficient mice. These findings highlight the potential of NCATS-SM7270 as a specific inhibitor of NOX2 in protecting against NOX2-dependent cell death in mTBI.
Article
Microbiology
Hasnaa Maksouri, Dounia Darif, Jerome Estaquier, Myriam Riyad, Christophe Desterke, Meryem Lemrani, Pham My-Chan Dang, Khadija Akarid
Summary: This study evaluated the impact of Moroccan strains of L. major and L. tropica on PMNs. The results showed that L. tropica inhibited O-2(-) production, while L. major did not. Additionally, Leishmania soluble antigens from both species inhibited O-2(-) induction.
Article
Cell Biology
Yuliya Filina, Aida Gabdoulkhakova, Albert Rizvanov, Valentina Safronova
Summary: Phagocytes' functional activity and inflammation's development and resolution are determined by formylpeptide receptors (FPRs) signaling. Research has shown that different types of formylpeptide receptors, FPR1 and FPR2, activate distinct patterns of MAP kinase activity, with JNK involved in both Fpr1 and Fpr2 mediated activation of ROS production, while p38 MAPK and ERK are only involved in Fpr1 induced ROS generation.
CELLULAR SIGNALLING
(2022)
Article
Biochemistry & Molecular Biology
Paola Cuomo, Chiara Medaglia, Ivana Allocca, Angela Michela Immacolata Montone, Fabrizia Guerra, Serena Cabaro, Ernesto Mollo, Daniela Eletto, Marina Papaianni, Rosanna Capparelli
Summary: The study demonstrates that Caulerpin, a bis-indole alkaloid isolated from algae, can serve as a molecular antagonist of FPRs, reducing immune response against Hp culture filtrate by reverting FPR2-related signaling cascade and counteracting inflammatory reactions triggered by Hp peptide Hp(2-20). The findings suggest Caulerpin as a promising therapeutic or adjuvant agent for attenuating inflammation caused by Hp infection and its adverse clinical outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Momoko Akiyama, Ryosuke Ueki, Masataka Yanagawa, Mitsuhiro Abe, Michio Hiroshima, Yasushi Sako, Shinsuke Sando
Summary: In this study, a synthetic receptor agonist was designed using a DNA aptamer as a building block to fine-tune agonism. The developed synthetic partial agonist can regulate therapeutically relevant cellular activities by eliciting finely-tuned receptor signaling.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Pharmacology & Pharmacy
Alice Lallo, Sakshi Gulati, Maximilian W. Schenk, Garima Khandelwal, Ulrika Warpman Berglund, Ioannis S. Pateras, Christopher P. E. Chester, Therese M. Pham, Christina Kalderen, Kristopher K. Frese, Vassilis G. Gorgoulis, Crispin Miller, Fiona Blackhall, Thomas Helleday, Caroline Dive
BRITISH JOURNAL OF PHARMACOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Oleg Ursu, Jayme Holmes, Cristian G. Bologa, Jeremy J. Yang, Stephen L. Mathias, Vasileios Stathias, Dac-Trung Nguyen, Stephan Schurer, Tudor Oprea
NUCLEIC ACIDS RESEARCH
(2019)
Review
Pharmacology & Pharmacy
Andreu Bofill, Xavier Jalencas, Tudor Oprea, Jordi Mestres
DRUG DISCOVERY TODAY
(2019)
Article
Clinical Neurology
Anastasiya Nestsiarovich, Berit Kerner, Aurelien J. Mazurie, Daniel C. Cannon, Nathaniel G. Hurwitz, Yiliang Zhu, Stuart J. Nelson, Tudor Oprea, Mark L. Unruh, Annette S. Crisanti, Mauricio Tohen, Douglas J. Perkins, Christophe G. Lamberet
JOURNAL OF AFFECTIVE DISORDERS
(2019)
Review
Biochemistry & Molecular Biology
Tudor I. Oprea
Editorial Material
Biotechnology & Applied Microbiology
Melissa Haendel, Nicole Vasilevsky, Deepak Unni, Cristian Bologa, Nomi Harris, Heidi Rehm, Ada Hamosh, Gareth Baynam, Tudor Groza, Julie McMurry, Hugh Dawkins, Ana Rath, Courtney Thaxon, Giovanni Bocci, Marcin P. Joachimiak, Sebastian Koehler, Peter N. Robinson, Chris Mungall, Tudor I. Oprea
NATURE REVIEWS DRUG DISCOVERY
(2020)
Review
Pharmacology & Pharmacy
Alex Zhavoronkov, Quentin Vanhaelen, Tudor I. Oprea
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2020)
Review
Pharmacology & Pharmacy
Giovanni Bocci, Leslie Z. Benet, Tudor Oprea
DRUG DISCOVERY TODAY
(2019)
Correction
Biotechnology & Applied Microbiology
Erik Tambuyzer, Benjamin Vandendriessche, Christopher P. Austin, Philip J. Brooks, Kristina Larsson, Katherine I. Miller Needleman, James Valentine, Kay Davies, Stephen C. Groft, Robert Preti, Tudor I. Oprea, Marco Prunotto
NATURE REVIEWS DRUG DISCOVERY
(2020)
Review
Biotechnology & Applied Microbiology
Erik Tambuyzer, Benjamin Vandendriessche, Christopher P. Austin, Philip J. Brooks, Kristina Larsson, Katherine I. Miller Needleman, James Valentine, Kay Davies, Stephen C. Groft, Robert Preti, Tudor I. Oprea, Marco Prunotto
NATURE REVIEWS DRUG DISCOVERY
(2020)
Article
Endocrinology & Metabolism
Anastasiya Nestsiarovich, Bent Kerner, Aurelien J. Mazurie, Daniel C. Cannon, Nathaniel G. Hurwitz, Yiliang Zhu, Stuart J. Nelson, Tudor I. Oprea, Annette S. Crisanti, Mauricio Tohen, Douglas J. Perkins, Christophe G. Lambert
PSYCHONEUROENDOCRINOLOGY
(2020)
Article
Chemistry, Multidisciplinary
Gergely Zahoranszky-Kohalmi, Timothy Sheils, Tudor I. Oprea
JOURNAL OF CHEMINFORMATICS
(2020)
Editorial Material
Biotechnology & Applied Microbiology
Jeremy M. Levin, Tudor I. Oprea, Sagie Davidovich, Thomas Clozel, John P. Overington, Quentin Vanhaelen, Charles R. Cantor, Evelyne Bischof, Alex Zhavoronkov
NATURE BIOTECHNOLOGY
(2020)
Review
Chemistry, Multidisciplinary
Eugene N. Muratov, Jurgen Bajorath, Robert P. Sheridan, Igor Tetko, Dmitry Filimonov, Vladimir Poroikov, Tudor Oprea, Igor I. Baskin, Alexandre Varnek, Adrian Roitberg, Olexandr Isayev, Stefano Curtarolo, Denis Fourches, Yoram Cohen, Alan Aspuru-Guzik, David A. Winkler, Dimitris Agrafiotis, Artem Cherkasov, Alexander Tropsha
CHEMICAL SOCIETY REVIEWS
(2020)
Article
Biochemistry & Molecular Biology
Chetana M. Revankar, Cristian G. Bologa, Richard A. Pepermans, Geetanjali Sharma, Whitney K. Petrie, Sara N. Alcon, Angela S. Field, Chinnasamy Ramesh, Matthew A. Parker, Nikolay P. Savchuk, Larry A. Sklar, Helen J. Hathaway, Jeffrey B. Arterburn, Tudor Oprea, Eric R. Prossnitz
CELL CHEMICAL BIOLOGY
(2019)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)