Article
Chemistry, Medicinal
Qi Liang, Jianyu He, Xue Zhao, Yan Xue, Haiyue Zuo, Ru Xu, Yan Jin, Jing Wang, Qian Li, Xinfeng Zhao
Summary: This study introduced DNA-encoding techniques to rapidly and impartially discover hits derived from natural products with high throughput and efficiency, successfully synthesizing a diversified phenolic acid-focused library and obtaining effective phenolic acid derivatives through online selection.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Boeun Lee, Michelle Taylor, Suzy A. Griffin, Tamara McInnis, Nathalie Sumien, Robert H. Mach, Robert R. Luedtke
Summary: The study showed that N-phenylpiperazine analogs can selectively bind to the human D3 dopamine receptor with significant D3 vs. D2 binding selectivity, potentially leading to the development of pharmacotherapeutics for levodopa-induced dyskinesia in patients with Parkinson's disease.
Article
Biochemistry & Molecular Biology
Akiharu Ishida, Yasuyuki Okabe, Takeshi Matsushita, Tetsuya Sekiguchi, Takuya Nishio, Tatsuya Komagata, Masanori Iwaki, Hidenori Miyata, Jun Katagi, Atsushi Naganawa, Toru Maruyama, Akira Imagawa
Summary: This study investigated the relationship between in silico physicochemical properties and hERG and PLD, and found that the value of (cLogP) [2] + (pKa) [2] needs to be less than 110 to mitigate the toxicological liabilities. As a result, wellbalanced agonists such as amide 19 and benzimidazole 30 were identified.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Review
Endocrinology & Metabolism
Monica R. Gadelha, Luiz Eduardo Wildemberg, Leandro Kasuki
Summary: This article discusses the future perspectives of currently available SRLs, including the use of biomarkers of response and precision medicine, new formulations of these SRLs, and new drugs under development. Precision medicine based on biomarkers of response can help improve treatment decision-making and response rates. New formulations may improve patients' adherence to treatment and quality of life. New drugs may present higher efficacy than currently available drugs.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Chemistry, Medicinal
Antonios Drakopoulos, Dimitrios Moianos, Georgia-Myrto Prifti, Grigoris Zoidis, Michael Decker
Summary: This review presents different categories of ligand drugs and molecular tools for opioid receptors (ORs), emphasizing their properties and showcasing promising drug candidates.
Article
Medicine, General & Internal
Robert Pichler, Ognian Kalev, Berndt Tomancok, Michael Sonnberger, Daniela Ehrlich, Marina Hodolic
Summary: Somatostatin analogues, including first-generation analogues and pasireotide, are considered the first-line treatment for acromegaly, targeting different SSTR subtypes to improve therapeutic outcomes. Immunohistochemical analysis of SSTR subtypes may have predictive value for treatment response in patients with acromegaly, especially those with clinical relapse and complex clinical courses.
Article
Pharmacology & Pharmacy
Jamie J. Manning, Gabriel Rawcliffe, David B. Finlay, Michelle Glass
Summary: This study investigated the impact of phosphorylation modifications in a specific sequence of the CB1 receptor C-terminus on the translocation of Arrestin-2 and Arrestin-3. The results showed that these modifications partially contributed to the translocation of Arrestin, but complete inhibition was only achieved when all phosphorylation sites were mutated. Additionally, the dissociation of G proteins was also impaired proportionally to the extent of Arrestin translocation.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Niklas Rosier, Lukas Graetz, Hannes Schihada, Jan Moeller, Ali Isbilir, Laura J. Humphrys, Martin Nagl, Ulla Seibel, Martin J. Lohse, Steffen Pockes
Summary: The novel fluorescent H3R ligand UR-NR266 has been synthesized and characterized for its exceptional selectivity and pharmacological properties at the sub-nanomolar level. It shows fast association and dissociation kinetics at the H3R, making it a versatile pharmacological tool for analyzing future H3R ligands. UR-NR266 also exhibits low nonspecific binding and has been identified as a selective compound in off-target screening at 14 receptors.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Daniel G. Henriques, Elisa B. Lamback, Romulo S. Dezonne, Leandro Kasuki, Monica R. Gadelha
Summary: This review focuses on the most validated miRNAs involved in the pathogenesis of acromegaly and resistance to first-generation somatostatin receptor ligands (fg-SRL), as well as circulating miRNAs in acromegaly.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Medicinal
Alessandro Bonifazi, Fabio Del Bello, Gianfabio Giorgioni, Alessandro Piergentili, Elizabeth Saab, Luca Botticelli, Carlo Cifani, Emanuela Micioni Di Bonaventura, Maria Vittoria Micioni Di Bonaventura, Wilma Quaglia
Summary: Orexin-A and Orexin-B are highly conserved hypothalamic neuropeptides that mediate their effects through two distinct G protein-coupled receptors, OX1-R and OX2-R. They play important roles in various physiological functions such as sleep-wake cycle regulation, emotion, panic-like behaviors, anxiety/stress, food intake, and energy homeostasis. This review focuses on the medicinal chemistry aspects of small molecules acting as dual or subtype selective OX1-R/OX2-R agonists and antagonists, as well as radiolabeled OX-R ligands for molecular imaging.
MEDICINAL RESEARCH REVIEWS
(2023)
Review
Pharmacology & Pharmacy
Kenneth A. Jacobson, Zhan-Guo Gao, Pierre Matricon, Matthew T. Eddy, Jens Carlsson
Summary: Caffeine and adenosine, along with their interaction with the A(2A) receptor, play crucial roles in the brain, particularly in the protection of aging brain and potential treatments for various diseases. Understanding the atomic-level interaction with the A(2A) receptor has led to the development of diverse drug molecules. The focus has expanded from neurodegenerative diseases to include cancer immunotherapy.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Jian Zhao, Shimiao Wang, Sun Hee Kim, Sangdon Han, Elizabeth Rico-Bautista, Emmanuel Sturchler, Julie Nguyen, Hannah Tan, Christine Staley, Ana Karin Kusnetzow, Stephen F. Betz, Michael Johns, Lance Goulet, Rosa Luo, Melissa Fowler, Jon Athanacio, Stacy Markison, R. Scott Struthers, Yunfei Zhu
Summary: The activation of SST5 receptors strongly inhibits insulin secretion, and a newly discovered nonpeptide selective SST5 agonist shows potential for managing blood glucose levels in congenital HI patients. The agonist exhibits excellent potency and selectivity against other receptors and has promising pharmacokinetic profiles in animal models.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Pharmacology & Pharmacy
Maria Buur Nordskov Gabe, Laerke Smidt Gasbjerg, Sarina Gadgaard, Peter Lindquist, Jens Juul Holst, Mette Marie Rosenkilde
Summary: This study investigates the regulatory role of the GLP-2 system in the gut and bones by studying the effects of N-terminal truncations of human GLP-2 peptides on GLP-2 receptor activity and selectivity. The results show that the N-terminus of GLP-2 is crucial for GLP-2 receptor activity and selectivity. These findings provide a foundation for the development of tool compounds for further characterization of the GLP-2 system.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Chayma El Khamlichi, Flora Reverchon, Nadege Hervouet-Coste, Elodie Robin, Nicolas Chopin, Emmanuel Deau, Fahima Madouri, Cyril Guimpied, Cyril Colas, Arnaud Menuet, Asuka Inoue, Andrzej J. Bojarski, Gerald Guillaumet, Franck Suzenet, Eric Reiter, Severine Morisset-Lopez
Summary: This study demonstrates that Serodolin is a unique agonist/antagonist that modulates the biological functions of GPCRs through specific signaling pathways. Additionally, Serodolin has a significant analgesic effect on pain sensation and acts specifically through 5-HT7R. This research provides new insights into the molecular mechanism of 5-HT7R and the modulation of pain response.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Santhosh Kumar Nagarajan, Sathya Babu, Panneer Devaraju, Honglae Sohn, Thirumurthy Madhavan
Summary: In the past two decades, research on the structural biology of G-protein coupled receptors (GPCRs) has been increasing. Understanding the relationship between the structure and function of GPCRs is crucial as they play important roles in various signaling mechanisms in eukaryotic cells. This study focuses on the structural understanding of SSTR3-ligand binding, utilizing computational tools to gain insights into the complex functioning of the receptor and identify key physicochemical descriptors of SSTR3 ligands that influence their bioactivity.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2022)
Review
Pharmacology & Pharmacy
Daniel Hoyer, Andrew Allen, Laura H. Jacobson
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2020)
Article
Psychiatry
Andrew S. Gibbons, Daniel Hoyer, Brian Dean
Summary: A recent study found decreased mRNA expression of SMAD2 and SMAD4 in the dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia. Further investigation revealed lower levels of SMAD4 protein in the cortex of schizophrenia subjects, suggesting abnormalities in cortical TGFB-superfamily signalling in schizophrenia.
WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
(2021)
Article
Neurosciences
Ryan J. Keenan, Sara Oberrauch, Romke Bron, Cameron J. Nowell, Leesa M. Challis, Daniel Hoyer, Laura H. Jacobson
Summary: The research indicates that tau protein may impact the orexin system, including LC OX(1)Rs, shedding light on the mechanism of sleep/wake disturbances in AD and FTD.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Geriatrics & Gerontology
Sara Oberrauch, Jeremy A. Metha, Maddison L. Brian, Samuel A. Barnes, Travis J. Featherby, Andrew J. Lawrence, Daniel Hoyer, Carsten Murawski, Laura H. Jacobson
Summary: The study found that tau(-/-) mice showed significant changes in reward processing, which may help explain the aberrant reward-related behaviors in tauopathy patients.
NEUROBIOLOGY OF AGING
(2021)
Review
Pharmacology & Pharmacy
Nicholas M. Barnes, Gerard P. Ahern, Carine Becamel, Joel Bockaert, Michael Camilleri, Severine Chaumont-Dubel, Sylvie Claeysen, Kathryn A. Cunningham, Kevin C. Fone, Michael Gershon, Giuseppe Di Giovanni, Nathalie M. Goodfellow, Adam L. Halberstadt, Rachel M. Hartley, Gherici Hassaine, Katharine Herrick-Davis, Ruud Hovius, Enza Lacivita, Evelyn K. Lambe, Marcello Leopoldo, Finn Olav Levy, Sarah C. R. Lummis, Philippe Marin, Luc Maroteaux, Andrew C. McCreary, David L. Nelson, John F. Neumaier, Adrian Newman-Tancredi, Hugues Nury, Alexander Roberts, Bryan L. Roth, Anne Roumier, Gareth J. Sanger, Milt Teitler, Trevor Sharp, Carlos M. Villalon, Horst Vogel, Stephanie W. Watts, Daniel Hoyer
Summary: This review provides a comprehensive account of the classification and function of 5-hydroxytryptamine receptors, including how they are targeted for therapeutic benefit.
PHARMACOLOGICAL REVIEWS
(2021)
Article
Psychiatry
Daniel Perkins, Jerome Sarris, Susan Rossell, Yvonne Bonomo, David Forbes, Christopher Davey, Daniel Hoyer, Colleen Loo, Greg Murray, Sean Hood, Violeta Schubert, Nicole Leite Galvao-Coelho, Meaghen O'Donnell, Olivia Carter, Paul Liknaitzky, Martin Williams, Dan Siskind, David Penington, Michael Berk, David Castle
Summary: The text explores the renewed interest in the medical use of psychedelic substances and the potential benefits and therapeutic mechanisms. It emphasizes the need for rigorous research and trials to ensure safety and efficacy before widespread clinical translation.
AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY
(2021)
Article
Clinical Neurology
Jacob W. Clark, Heather Daykin, Jeremy A. Metha, Giancarlo Allocca, Daniel Hoyer, Sean P. A. Drummond, Laura H. Jacobson
Summary: Sleep disruption, particularly REM sleep disruption, impairs fear inhibition in animals and humans. The study shows that suvorexant, which increases REM sleep, enhances fear extinction compared to zolpidem, which decreases REM sleep. Mice treated with suvorexant achieved faster fear extinction during LD cycle-shifts, while retention of safety memory was not influenced by either treatment.
Article
Pharmacology & Pharmacy
Stephen P. H. Alexander, Arthur Christopoulos, Anthony P. Davenport, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Adam J. Pawson, Christopher Southan, Jamie A. Davies, Maria Pia Abbracchio, Wayne Alexander, Khaled Al-hosaini, Magnus Baeck, Nicholas M. Barnes, Ross Bathgate, Jean-Martin Beaulieu, Kenneth E. Bernstein, Bernhard Bettler, Nigel J. M. Birdsall, Victoria Blaho, Francois Boulay, Corinne Bousquet, Hans Braeuner-Osborne, Geoffrey Burnstock, Girolamo Calo, Justo P. Castano, KevinJ Catt, Stefania Ceruti, Paul Chazot, Nan Chiang, Bice Chini, Jerold Chun, Antonia Cianciulli, Olivier Civelli, Lucie H. Clapp, Rejean Couture, Zsolt Csaba, Claes Dahlgren, Gordon Dent, Khuraijam Dhanachandra Singh, Steven D. Douglas, Pascal Dournaud, Satoru Eguchi, Emanuel Escher, Edward J. Filardo, Tung Fong, Marta Fumagalli, Raul R. Gainetdinov, Marc de Gasparo, Craig Gerard, Marvin Gershengorn, Fernand Gobeil, Theodore L. Goodfriend, Cyril Goudet, Karen J. Gregory, Andrew L. Gundlach, Joerg Hamann, Julien Hanson, Richard L. Hauger, Debbie L. Hay, Akos Heinemann, Morley D. Hollenberg, Nicholas D. Holliday, Mastgugu Horiuchi, Daniel Hoyer, Laszlo Hunyady, Ahsan Husain, Adriaan P. IJzerman, Tadashi Inagami, Kenneth A. Jacobson, Robert T. Jensen, Ralf Jockers, Deepa Jonnalagadda, Sadashiva Karnik, Klemens Kaupmann, Jacqueline Kemp, Charles Kennedy, Yasuyuki Kihara, Takio Kitazawa, Pawel Kozielewicz, Hans-Juergen Kreienkamp, Jyrki P. Kukkonen, Tobias Langenhan, Katie Leach, Davide Lecca, John D. Lee, Susan E. Leeman, Jerome Leprince, Xaria X. Li, Tom Lloyd Williams, Stephen J. Lolait, Amelie Lupp, Robyn Macrae, Janet Maguire, Jean Mazella, Craig A. McArdle, Shlomo Melmed, Martin C. Michel, Laurence J. Miller, Vincenzo Mitolo, Bernard Mouillac, Christa E. Mueller, Philip Murphy, Jean-Louis Nahon, Tony Ngo, Xavier Norel, Duuamene Nyimanu, Anne-Marie Ocarroll, Stefan Offermanns, Maria Antonietta Panaro, Marc Parmentier, Roger G. Pertwee, Jean-Philippe Pin, Eric R. Prossnitz, Mark Quinn, Rithwik Ramachandran, Manisha Ray, Rainer K. Reinscheid, Philippe Rondard, G. Enrico Rovati, Chiara Ruzza, Gareth J. Sanger, Torsten Schoeneberg, Gunnar Schulte, Stefan Schulz, Deborah L. Segaloff, Charles N. Serhan, Leigh A. Stoddart, Yukihiko Sugimoto, Roger Summers, Valerie P. Tan, David Thal, Walter (Wally) Thomas, PieterB M. W. M. Timmermans, Kalyan Tirupula, Giovanni Tulipano, Hamiyet Unal, Thomas Unger, Celine Valant, Patrick Vanderheyden, David Vaudry, Hubert Vaudry, Jean-Pierre Vilardaga, Christopher S. Walker, Ji Ming Wang, Donald T. Ward, Hans-Juergen Wester, Gary B. Willars, Trent M. Woodruff, Chengcan Yao, Richard D. Ye
Summary: The Concise Guide to PHARMACOLOGY 2021/22 presents concise overviews of nearly 1900 human drug targets with an emphasis on selective pharmacology, along with links to a more detailed knowledgebase. It serves as a permanent, citable record for researchers, providing useful information in the field of pharmacology.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Ryan J. Keenan, Heather Daykin, Jiahui Chu, Linda Cornthwaite-Duncan, Giancarlo Allocca, Daniel Hoyer, Laura H. Jacobson
Summary: This study investigates the effects of sleep-promoting compounds in transgenic mouse models of tauopathy and finds that these compounds can effectively improve sleep disturbances. The results also suggest that there may be gender differences in the response to hypnotics, which could have implications for the treatment of neurodegenerative disorders in humans.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Medicine, General & Internal
Laura H. Jacobson, Daniel Hoyer, Luis de Lecea
Summary: Hypocretins, also known as orexins, are neuropeptides produced in the lateral hypothalamus that play a crucial role in various neurophysiological functions such as sleep, arousal, feeding, and cognition. Loss of Hcrt cells in humans leads to narcolepsy, demonstrating the essential role of the Hcrt system in sleep/wake stability. The development of Hcrt receptor antagonists as a new class of drugs to treat insomnia has been clinically validated.
JOURNAL OF INTERNAL MEDICINE
(2022)
Editorial Material
Multidisciplinary Sciences
Laura H. Jacobson, Daniel Hoyer
Review
Neurosciences
Natasha C. Dale, Daniel Hoyer, Laura H. Jacobson, Kevin D. G. Pfleger, Elizabeth K. M. Johnstone
Summary: The orexin system consists of two G protein-coupled receptors, OX1 and OX2 receptors, along with two endogenous agonists. Orexin receptor coupling is diverse and can vary depending on tissue, cell, and context. Ligands, receptor-protein interactions, and cellular environment play important roles in the G protein coupling profiles of the orexin receptors. This has implications for understanding the function of the orexin system and developing drugs targeting it.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Behavioral Sciences
Lauren E. Bleakley, Ryan J. Keenan, Rachel D. Graven, Jeremy A. Metha, Sherie Ma, Heather Daykin, Linda Cornthwaite-Duncan, Daniel Hoyer, Christopher A. Reid, Laura H. Jacobson
Summary: HCN1 channels do not play a major role in sleep architecture or modulation of vigilance states. However, loss of these channels significantly alters underlying neuronal activity within these states which may have functional consequences.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Ryan J. Keenan, Heather Daykin, Jeremy Metha, Linda Cornthwaite-Duncan, David K. Wright, Kyra Clarke, Sara Oberrauch, Maddison Brian, Sarah Stephenson, Cameron J. Nowell, Giancarlo Allocca, Kevin J. Barnham, Daniel Hoyer, Laura H. Jacobson
Summary: This study found that pharmacologically reducing hyperarousal can correct tau-induced sleep and cognitive deficits, but this effect was only observed in male mice. In addition, tauopathy caused disruptions of OX2 receptor signaling in a sex-dependent manner.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Neurosciences
Daniel Hoyer
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
