Article
Engineering, Biomedical
Peng Yan, Yang Luo, Xinyang Li, Yingmin Li, Yi Wang, Jian Wu, Shaobing Zhou
Summary: The combination of a nanovaccine and A2AR antagonist presented in this study can trigger an antitumor immune response while inhibiting immunosuppression in the tumor microenvironment.
ADVANCED HEALTHCARE MATERIALS
(2021)
Review
Biochemistry & Molecular Biology
Catia Lambertucci, Gabriella Marucci, Daniela Catarzi, Vittoria Colotta, Beatrice Francucci, Andrea Spinaci, Flavia Varano, Rosaria Volpini
Summary: Endogenous nucleoside adenosine, particularly the A(2A) subtype, plays an important role in the treatment of neurodegenerative disorders involving neuroinflammation. Inhibition of A(2A) adenosine receptors exhibits neuroprotective effects and counteracts neuroinflammatory processes. The approval of A(2A) adenosine receptor antagonist istradefylline opens up new therapeutic opportunities for these diseases.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Binfen Shao, Xuehui Huang, Funeng Xu, Jingmei Pan, Yi Wang, Shaobing Zhou
Summary: A pH-responsive polymersome has been developed in this study, which can release drugs in the acidic tumor microenvironment, deplete T cells, block A2A receptor, and enhance cancer immunotherapy efficacy.
Review
Medicine, Research & Experimental
Elizabeth A. Thompson, Jonathan D. Powell
Summary: Cancer immunotherapy has revolutionized cancer treatment, but there are still many potential immune evasion or suppression mechanisms, with adenosinergic signaling being a significant pathway. Clinical trials targeting the adenosine pathway are ongoing, with the potential to enhance immunotherapy efficacy further.
ANNUAL REVIEW OF MEDICINE, VOL 72, 2021
(2021)
Article
Pharmacology & Pharmacy
Luke J. Hamilton, Michaela Walker, Mahesh Pattabiraman, Haizhen A. Zhong, Brandon Luedtke, Surabhi Chandra
Summary: The study generated a novel isomer of curcumin using photochemical methods and found that this compound binds to two receptor subtypes with K-i values of 5μM and 7μM, respectively. The results showed that this isomer is non-toxic to cells and may potentially be developed as a new class of non-opioid analgesics.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Benjamin Friedman, Ane Larranaga-Vera, Cristina M. Castro, Carmen Corciulo, Piul Rabbani, Bruce N. Cronstein
Summary: The pathogenesis of osteoarthritis (OA) is related to imbalanced chondrocyte homeostasis and increased cellular senescence in cartilage. Activation of adenosine A2A receptor (A2AR) promotes cartilage regeneration and chondrocyte homeostasis. A2AR activation reduces chondrocyte senescence and attenuates OA progression.
Review
Immunology
Changfa Sun, Bochu Wang, Shilei Hao
Summary: The adenosine-A2AR pathway plays a crucial role in regulating immune responses and tumor progression. Blocking this pathway can inhibit tumor growth and has potential synergistic effects with CAR T cell therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Michal Zaluski, Dorota Lazewska, Piotr Jasko, Ewelina Honkisz-Orzechowska, Kamil J. Kuder, Andreas Brockmann, Gniewomir Latacz, Malgorzata Zygmunt, Maria Kaleta, Beril Anita Greser, Agnieszka Olejarz-Maciej, Magdalena Jastrzebska-Wiesek, Christin Vielmuth, Christa E. Mueller, Katarzyna Kiec-Kononowicz
Summary: This study synthesized 25 novel xanthine derivatives with potential anti-inflammatory activity and explored their effects on neurodegenerative diseases such as Parkinson's disease. Three compounds were selected for further studies and showed good metabolic stability and anti-inflammatory activity in vitro and in vivo. Further optimization of these compounds and exploration of their therapeutic potential in neurodegenerative diseases are warranted.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Akihisa Mori, Brittany Cross, Shinichi Uchida, Jill Kerrick Walker, Robert Ristuccia
Summary: Adenosine is widely distributed in the central and peripheral nervous systems as a key neuromodulator, with implications in the pathogenesis of neurodegenerative disorders, especially in ALS. Motor neurons affected in ALS are responsive to adenosine receptor function, with accumulating evidence supporting the benefits of adenosine A(2A) receptor antagonism.
Review
Biochemistry & Molecular Biology
Regis Guieu, Clara Degioanni, Julien Fromonot, Lucille De Maria, Jean Ruf, Jean Claude Deharo, Michele Brignole
Summary: Adenosine plays a role in neuro-humoral syncope through its interaction with different receptor subtypes. The modulation of ion channels, calcium channels, and cAMP production are involved in adenosine's effects on the cardiovascular system. Adenosine receptor antagonists may be useful in the treatment of syncope.
Article
Biochemistry & Molecular Biology
Hector Godoy-Marin, Romain Duroux, Kenneth A. Jacobson, Concepcio Soler, Hildegard Colino-Lage, Veronica Jimenez-Sabado, Jose Montiel, Leif Hove-Madsen, Francisco Ciruela
Summary: Atrial fibrillation (AF) is influenced by various factors such as oxidative stress, calcium overload, inflammation, as well as adenosine and its receptors. Studies have found increased A2AR expression in the right atrium of AF patients, elevated levels of adenosine content in plasma, and reduced ADA activity. Importantly, there is a positive correlation between A2AR expression in PBMCs and in the right atrium.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Andrea Spinaci, Catia Lambertucci, Michela Buccioni, Diego Dal Ben, Claudia Graiff, Maria Cristina Barbalace, Silvana Hrelia, Cristina Angeloni, Seyed Khosrow Tayebati, Massimo Ubaldi, Alessio Masi, Karl-Norbert Klotz, Rosaria Volpini, Gabriella Marucci
Summary: In this study, two series of compounds based on purine and triazolotriazine scaffolds were synthesized to find novel ligands for the A(2A) adenosine receptor (A(2A)AR). It was found that some compounds had high affinity for A(2A)AR and that compound 13 exhibited anti-inflammatory properties in microglial cells. Molecular modeling studies supported the binding affinity data and revealed that substitution at specific positions is necessary for interchangeability between triazolotriazine and purine scaffolds.
Article
Chemistry, Medicinal
Raphael Bolteau, Romain Duroux, Amelie Laversin, Brandon Vreulz, Anna Shiriaeva, Benjamin Stauch, Gye Won Han, Vadim Cherezov, Nicolas Renault, Amelie Barczyk, Severine Ravez, Mathilde Coevoet, Patricia Melnyk, Maxime Liberelle, Said Yous
Summary: The past fifty years have seen an increase in the prevalence of neurodegenerative diseases, but current treatments only provide symptomatic relief, leading to the need for new therapeutic targets. This paper focuses on the adenosine A2A receptor (A2AAR) as a potential target, reporting the design, synthesis, and pharmacological analysis of quinazoline derivatives as high-efficiency A2AAR antagonists. Through virtual screening, a series of 2-aminoquinazoline compounds were identified, with one compound (21a, Ki= 20 nM) showing promising affinity towards A2AAR. This ligand was crystallized in complex with A2AAR, confirming predicted docking poses and opening up opportunities for further optimization to develop selective ligands for specific adenosine receptor subtypes.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Zhi Li, Lijuan Kou, Xinzhen Fu, Zeping Xie, Maolei Xu, Lin Guo, Tiantian Lin, Shizhou Gong, Shumin Zhang, Ming Liu
Summary: A series of novel dual A(2A)/A(2B) AR antagonists were designed and synthesized based on a triazole-pyrimidine-methylbenzonitrile core. Compound 7i displayed promising inhibitory activity on A(2B) AR and higher potency in IL-2 production compared to AB928. Molecular docking studies supported the rationality of the design and the activity of compound 7i.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
P. Boknik, J. Eskandar, B. Hofmann, N. Zimmermann, J. Neumann, U. Gergs
Summary: This review provides an overview of the localization and role of cardiac A(2A)-adenosine receptors, as well as their potential involvement in relevant cardiac pathologies. The review also discusses the cardiac utility of A(2A)-AR as therapeutic targets and identifies gaps in knowledge for future research.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Organic
Li Xiao, Yilin Zheng, Qiong Xie, Liming Shao
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2017)
Article
Chemistry, Medicinal
Yafei Huang, Mingcheng Yu, Nannan Sun, Ting Tang, Fazhi Yu, Xiaoxia Song, Qiong Xie, Wei Fu, Liming Shao, Yonghui Wang
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Xicheng Yang, Jian Shen, Lulu Jiang, Wei Li, Mingcheng Yu, Guanxing Pan, Yurong Yan, Chenghan Zhang, Wanwan Jia, Li Xiao, Haihua Yu, Hao Chen, Yilin Zheng, Linqian Yu, Qiong Xie, Lu Zhou, Liming Shao
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Organic
Fazhi Yu, Runyu Mao, Mingcheng Yu, Xianfeng Gu, Yonghui Wang
JOURNAL OF ORGANIC CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Yan Zhu, Nannan Sun, Mingcheng Yu, Huimin Guo, Qiong Xie, Yonghui Wang
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Nannan Sun, Yafei Huang, Mingcheng Yu, Yunpeng Zhao, Ji-An Chen, Chenyu Zhu, Meiqi Song, Huimin Guo, Qiong Xie, Yonghui Wang
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Yuehan Xia, Mingcheng Yu, Yunpeng Zhao, Li Xia, Yafei Huang, Nannan Sun, Meiqi Song, Huimin Guo, Yunyi Zhang, Di Zhu, Qiong Xie, Yonghui Wang
Summary: ROR gamma t agonists, such as tetrahydroquinoline compound 8g and benzomorpholine compound 9g, were identified as potent compounds with high ROR gamma t agonistic activity. These compounds showed good activity in various assays and may have potential for cancer immunotherapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Nannan Sun, Qiong Xie, Yongjun Dang, Yonghui Wang
Summary: ROR gamma t is a potential drug target for autoimmune diseases with complex relationship between agonist lock and inverse agonism. Different inverse agonists adopt different interference mechanisms.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Ruomeng Qiu, Mingcheng Yu, Juwen Gong, Jinlong Tian, Yafei Huang, Yonghui Wang, Qiong Xie
Summary: The nuclear receptor RORγt plays a crucial role in regulating the differentiation and proliferation of Th17 cells, which have shown potential antitumor effects by activating CD8+ T cells. Agonists of RORγt may serve as small molecule therapeutics for cancer immunotherapy, and the development of novel RORγt agonists with improved biological responses opens up possibilities for further optimization in this field.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Ji-An Chen, Hui Ma, Zehui Liu, Jinlong Tian, Sisi Lu, Wenqing Fang, Shuyin Ze, Weiqiang Lu, Qiong Xie, Jin Huang, Yonghui Wang
Summary: The study proposed a novel strategy for treating inflammatory bowel disease (IBD) by using dual-targeting inhibitors of RORγt and DHODH. The experimental results demonstrated that these inhibitors could effectively reduce Th17 cell differentiation, attenuate T cell activation, and exhibit significant anti-inflammatory effects in a mouse model.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
En-ming Tian, Ming-cheng Yu, Mei Feng, Li-xue Lu, Cheng-long Liu, Li-an Shen, Yong-hui Wang, Qiong Xie, Di Zhu
Summary: The study demonstrates that JG-1, a potent and selective small-molecule ROR gamma t agonist, promotes Th17 cells differentiation and inhibits regulatory T cells, leading to robust tumor growth inhibition in multiple syngeneic models. JG-1 also shows a synergistic effect with CTLA-4 antibody, indicating its potential as a promising therapeutic agent for tumor immunity.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Chemistry, Medicinal
Fazhi Yu, Chenyu Zhu, Shuyin Ze, Haojie Wang, Xinyu Yang, Mingyao Liu, Qiong Xie, Weiqiang Lu, Yonghui Wang
Summary: Compound 57 demonstrates potential as a novel A(2A) receptor antagonist in cancer immunotherapy, enhancing T cell activation and inhibiting adenosine levels in the tumor microenvironment.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Kang Qian, Xiaoyan Bao, Yixian Li, Pengzhen Wang, Qian Guo, Peng Yang, Shuting Xu, Fazhi Yu, Ran Meng, Yunlong Cheng, Dongyu Sheng, Jinxu Cao, Minjun Xu, Jing Wu, Tianying Wang, Yonghui Wang, Qiong Xie, Wei Lu, Qizhi Zhang
Summary: Mitochondrial dysfunction in Alzheimer's disease has shown promise as a therapeutic target. This study developed a multifunctional hybrid peptide HNSS and a suitable peptide delivery system to repair and protect mitochondria, leading to improved outcomes in disease-related damage.
