Article
Chemistry, Multidisciplinary
Thais Gazzi, Benjamin Brennecke, Kenneth Atz, Claudia Korn, David Sykes, Gabriel Forn-Cuni, Patrick Pfaff, Roman C. Sarott, Matthias Westphal, Yelena Mostinski, Leonard Mach, Malgorzata Wasinska-Kalwa, Marie Weise, Bradley L. Hoare, Tamara Miljus, Maira Mexi, Nicolas Roth, Eline J. Koers, Wolfgang Guba, Andre Alker, Arne C. Rufer, Eric A. Kusznir, Sylwia Huber, Catarina Raposo, Elisabeth A. Zirwes, Anja Osterwald, Anto Pavlovic, Svenja Moes, Jennifer Beck, Matthias Nettekoven, Irene Benito-Cuesta, Teresa Grande, Faye Drawnel, Gabriella Widmer, Daniela Holzer, Tom van der Wel, Harpreet Mandhair, Michael Honer, Jurgen Fingerle, Joerg Scheffel, Johannes Broichhagen, Klaus Gawrisch, Julian Romero, Cecilia J. Hillard, Zoltan V. Varga, Mario van der Stelt, Pal Pacher, Jurg Gertsch, Christoph Ullmer, Peter J. McCormick, Sergio Oddi, Herman P. Spaink, Mauro Maccarrone, Dmitry B. Veprintsev, Erick M. Carreira, Uwe Grether, Marc Nazare
Summary: This study reports the development of a novel fluorescent CB2R agonist probe that can detect CB2R in living cells and zebrafish larvae. These findings contribute to the clinical translatability of CB2R-based drugs.
Article
Neurosciences
Nico Reusch, Kishore Aravind Ravichandran, Bolanle Fatimat Olabiyi, Joanna Agnieszka Komorowska-Mueller, Jan N. Hansen, Thomas Ulas, Marc Beyer, Andreas Zimmer, Anne-Caroline Schmoele
Summary: Tight regulation of microglial activity is crucial for precise responses to threats, as uncontrolled activity can be neurotoxic. Cannabinoid receptor 2 (CB2) signaling plays a key role in controlling microglial homeostasis and activation, impacting the response to Toll-like receptor (TLR) mediated activation. The deletion of CB2 leads to dampened transcriptional response and distinct gene expression profiles in microglia, influencing their activation programs.
Article
Chemistry, Multidisciplinary
Roman C. Sarott, Alexander E. G. Viray, Patrick Pfaff, Anastasiia Sadybekov, Gabriela Rajic, Vsevolod Katritch, Erick M. Carreira, James A. Frank
Summary: CB2 receptor is a promising target for treating neuroinflammation and other diseases, but the lack of understanding of its complex signaling complicates therapeutic exploitation. A study demonstrates how the CB2 agonist HU308 affects cytosolic Ca2+ levels in cells and tissues, and shows the utility of chemical photoswitches for real-time control and monitoring of CB2 signaling.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Biochemistry & Molecular Biology
Valeria Gasperi, Tatiana Guzzo, Alessandra Topai, Nicola Gambacorta, Fulvio Ciriaco, Orazio Nicolotti, Mauro Maccarrone
Summary: In the past decade, there has been a significant focus on developing selective modulators of the type-2 cannabinoid receptor (CB2) to target endocannabinoid signaling in humans. CB2 plays an active role in regulating various physiological and pathological processes, making it a promising target for therapeutic drugs. Recent studies have highlighted the protective effects of CB2 in central nervous system disorders, bone and synovial diseases, and cancer. Advances in the development of CB2 agonists have been correlated with different chemical classes and diverse therapeutic applications, and the elucidation of CB2 tertiary structure has provided new insights for the design of more selective agonists.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Biology
Bitya Raphael-Mizrahi, Malka Attar-Namdar, Mukesh Chourasia, Maria G. Cascio, Avital Shurki, Joseph Tam, Moshe Neuman, Neta Rimmerman, Zvi Vogel, Arie Shteyer, Roger G. Pertwee, Andreas Zimmer, Natalya M. Kogan, Itai Bab, Yankel Gabet, Mone Zaidi
Summary: The endocannabinoid system, consisting of OGP and CB2, plays an important role in maintaining bone health and preventing age-related bone loss. OGP acts as an agonist and positive allosteric modulator of CB2, and its decrease in circulation with age is associated with bone loss in premenopausal women and adult mice.
Article
Chemistry, Medicinal
Daniel Gundel, Winnie Deuther-Conrad, Lea Ueberham, Sarandeep Kaur, Elina Otikova, Rodrigo Teodoro, Magali Toussaint, Thu Hang Lai, Oliver Clauss, Matthias Scheunemann, Guy Bormans, Michael Bachmann, Klaus Kopka, Peter Brust, Rares-Petru Moldovan
Summary: The cannabinoid receptor type 2 (CB2R) is an ideal target for the diagnosis and therapy of neurodegenerative diseases and cancer. This study introduces a novel F-18-labeled radioligand that can efficiently image upregulated CB2R expression.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Harvey F. Fulo, Amal Shoeib, Christian Cabanlong, Alexander H. Williams, Chang-Guo Zhan, Paul L. Prather, Gregory B. Dudley
Summary: Synthetic indole cannabinoids characterized by modifications in the molecule structure can result in new ligands with high affinity and selectivity for human CB2 receptors.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Kangtai Xu, Yifei Wu, Zhuangzhuang Tian, Yuanfan Xu, Chaoran Wu, Zilong Wang
Summary: Pain, especially chronic pain, has a significant impact on patients' quality of life. Cannabinoids have shown potent analgesic effects in preclinical pain models by acting as agonists of CB1 and CB2 receptors. While the activation of CB1 receptors is associated with psychotropic adverse effects, the promising target for pain treatment is the CB2 receptors primarily expressed in immune cells. Microglia, as resident immune cells in the central nervous system, play a critical role in chronic pain, and CB2 receptors regulate their activity and function. This review focuses on the role of microglial CB2 receptors in spinal nociceptive circuitry and their implications for selective CB2 receptor agonist-mediated analgesia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Aboagyewaah Oppong-Damoah, Brenda Marie Gannon, Kevin Sean Murnane
Summary: CB2 receptor agonists in the endocannabinoid system are considered potential targets for treating alcohol use disorder (AUD) as they can modulate the reward pathway, reduce abuse-related effects, reverse neuroinflammation, improve cognition, and exhibit anti-inflammatory and neuroprotective effects without the psychiatric side effects of CB1 antagonists.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2022)
Review
Behavioral Sciences
Savanah L. Saldana-Shumaker, Alexander J. Grenning, Christopher W. Cunningham
Summary: This review highlights recent advances in synthetic cannabinoid receptor chemistry and pharmacology, including new CB1R and CB2R selective probes, rational approaches to the design of peripherally-restricted agents, and structural classes of positive and negative allosteric modulators of CB1R and CB2R.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2021)
Review
Biochemistry & Molecular Biology
Barbara Vuic, Tina Milos, Lucija Tudor, Marcela Konjevod, Matea Nikolac Perkovic, Maja Jazvinscak Jembrek, Gordana Nedic Erjavec, Dubravka Svob Strac
Summary: Neurodegenerative diseases, characterized by protein aggregation in the brain, can be influenced by the activation of CB2 receptors in the endocannabinoid system. Studies suggest that activating CB2 receptors has potential benefits in reducing protein aggregation-based pathology, attenuating inflammation, and alleviating dementia-related symptoms.
Article
Hematology
Cheng Yin Yuan, Vivian Zhou, Garrett Sauber, Todd Stollenwerk, Richard Komorowski, Alicia Lopez, Rosa Maria Tolon, Julian Romero, Cecilia J. Hillard, William R. Drobyski
Summary: The type 2 cannabinoid receptor CB2R plays a critical role in GVHD regulation, with effective therapeutic targeting depending on agonist signaling characteristics and receptor selectivity in conjunction with the composition of pathogenic immune effector cells.
Article
Medicine, Research & Experimental
Sandra Georgy Chafik, Haidy E. Michel, Ebtehal El-Demerdash
Summary: This study aimed to investigate the potential protective effects of a selective CB2 receptor agonist, 1-phenylisatin, on acute nephrotoxicity induced by cisplatin. The results showed that 1-phenylisatin significantly mitigated the damage to the kidneys caused by cisplatin through its anti-apoptotic, anti-inflammatory, and antioxidant effects. These effects were mainly mediated through the CB2 receptor.
Article
Chemistry, Medicinal
Yaliang Tang, Barbara Wolk, Ryan Nolan, Caitlin E. Scott, Debra A. Kendall
Summary: Testing four ABK5 derivatives revealed that ABK5-1 and ABK5-2 have higher affinity and efficacy as CB2-selective agonists, while maintaining subtype selectivity. These compounds showed potential for treating inflammation with stronger effects observed in ABK5-1.
Review
Neurosciences
Shuangtao Li, Yuanbing Huang, Lijun Yu, Xiaoyu Ji, Jie Wu
Summary: Cannabinoids, isolated from cannabis and present in animal nervous and immune systems, have shown promising clinical medicinal value, particularly in the field of neurodegenerative diseases such as Alzheimer's disease. This review explores the therapeutic potential of cannabinoids in treating Alzheimer's disease, highlighting their interactions with different endocannabinoid receptor subtypes and the role of the endocannabinoid system in this disease. The underlying mechanisms and potential usefulness of cannabinoids in clinical treatment are also discussed.
CURRENT NEUROPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Doha M. Beltagy, Nagat F. Nawar, Tarek M. Mohamed, Ehab Tousson, Mai M. El-Keey
Summary: This study aimed to evaluate the protective role of nanocurcumin as an antioxidant and anti-inflammatory agent, and its synergistic effects with Donepezil in the treatment of Alzheimer's disease in rats. The results showed that treatment with nanocurcumin improved memory, locomotion, and neuronal differentiation by activating the PI3K/AKT/GSK-3 beta pathway.
PROSTAGLANDINS & OTHER LIPID MEDIATORS
(2024)