Article
Biochemistry & Molecular Biology
Alex Disney, Keith M. Olson, Amanda M. Shafer, Sierra C. Moore, Jessica P. Anand, John R. Traynor, Stephen M. Husbands
Summary: The study designed and synthesized an orvinol antagonist, 14, which showed no agonist activity in vitro, and was at least equally effective as naloxone in reversing the effects of mu-opioid receptor agonists in vivo.
ACS CHEMICAL NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Zoe Li, Jie Liu, Fan Dong, Nancy Chang, Ruili Huang, Menghang Xia, Tucker A. Patterson, Huixiao Hong
Summary: The United States is facing a severe opioid crisis, with increasing numbers of deaths caused by both prescription and illegal opioids over the past two decades. Opioids are important for pain treatment but also highly addictive, making it difficult to combat this public health issue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Tao Che, Bryan L. Roth
Summary: This article explores the molecular basis of opioid receptor signaling, including the binding of opioids to receptors and the molecular determinants of signaling pathways. Additionally, the synergy between computational biology and medicinal chemistry is mentioned as a means to expedite the discovery of more effective and safer opioid compounds.
Article
Chemistry, Medicinal
Maree T. Smith, Dehui Kong, Andy Kuo, Mohammad Z. Imam, Craig M. Williams
Summary: The opioid crisis has increased the demand for novel opioid analgesics that have superior profiles compared to morphine. This Perspective reviews and discusses the multitargeted opioid ligand strategy for discovering such analgesics. Dual-targeted mu-opioid/delta-opioid (MOP/DOP) ligands with strong DOP antagonist potency and without DOP or kappa-opioid (KOP) agonist activity are promising candidates. Dual-targeted MOP/NOP partial agonists also show potential. The pharmacologic template of cebranopadol, a full agonist at MOP, DOP, and NOP receptors, and a partial agonist at KOP receptor, should be avoided due to its poor therapeutic indices.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Pooja Parishar, Neha Sehgal, Soumya Iyengar
Summary: The study found high expression of δ-OR mRNA in song control and auditory nuclei of male zebra finches, suggesting a potential role in modulating singing, song learning, and spatial learning.
Article
Biochemistry & Molecular Biology
Wenjie Zhou, Yanhua Li, Xiaojing Meng, An Liu, Yu Mao, Xia Zhu, Qian Meng, Yan Jin, Zhi Zhang, Wenjuan Tao
Summary: This study indicates that anxiety is linked to different stages of pain, with DOR1 and DOR2 playing distinct roles in modulating excitatory pathways in the CeA. The findings suggest a functional switching of DOR1 and DOR2 associated with anxiety states at different stages of pain.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Hongguang Ma, Mengchu Li, Piyusha P. Pagare, Huiqun Wang, Nima Nassehi, Edna J. Santos, S. Stevens Negus, Dana E. Selley, Yan Zhang
Summary: This study synthesized a series of bivalent ligands to investigate the functional interactions between opioid and chemokine receptors. Compound 1a showed promising antinociceptive effect and may serve as a novel chemical probe for developing more potent bivalent ligands for chronic pain management.
BIOORGANIC CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Charles P. France, Gerard P. Ahern, Saadyah Averick, Alex Disney, Heather A. Enright, Babak Esmaeli-Azad, Arianna Federico, Lisa R. Gerak, Stephen M. Husbands, Benedict Kolber, Edmond Y. Lau, Victoria Lao, David R. Maguire, Michael A. Malfatti, Girardo Martinez, Brian P. Mayer, Marco Pravetoni, Niaz Sahibzada, Phil Skolnick, Evan Y. Snyder, Nestor Tomycz, Carlos A. Valdez, Jim Zapf
Summary: The only medication available to prevent and treat opioid overdose is naloxone, approved by the FDA nearly 50 years ago. Due to its limitations, a scientific meeting was convened by NIAID/NIH to explore emerging alternative approaches for treating opioid overdose in the event of weaponization of synthetic opioids. This meeting discussed new approaches such as intranasal nalmefene, methocinnamox, covalent naloxone nanoparticles, serotonin receptor agonists, fentanyl-binding cyclodextrin scaffolds, detoxifying biomimetic nanosponge decoy receptors, and antibody-based strategies.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Chemistry, Medicinal
Hongguang Ma, Huiqun Wang, James C. Gillespie, Rolando E. Mendez, Dana E. Selley, Yan Zhang
Summary: This study reported the application of a nitrogen-walk approach in developing novel opioid ligands, showing that introducing a nitrogen atom can maintain excellent binding affinity and induce a functional switch at the MOR. Computational investigations provided supportive evidence and explanations for the in vitro results, contributing to the rational design of low efficacy MOR ligands for opioid use disorder therapeutics.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Public, Environmental & Occupational Health
Sinisa Skocibusic, Nera Zivlak-Radulovic, Mevludin Hasanovic, Hassan Awad, Dragana Karan-Krizanac, Nermana Mehic-Basara, Tomislav Rukavina
Summary: This study found that opiate addicts on opioid substitution treatment have a higher risk of HCV infection if they have personality dysfunction, particularly in terms of self-respect, enduring relationships, and cooperativity.
FRONTIERS IN PUBLIC HEALTH
(2022)
Review
Pharmacology & Pharmacy
Martin L. Dalefield, Brittany Scouller, Rabia Bibi, Bronwyn M. Kivell
Summary: Kappa-opioid receptors have wide-ranging effects on various physiological processes and hold therapeutic potential for pain, pruritis, and other diseases. However, adverse effects limit their clinical use, highlighting the need for further development.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Zheng Dong, Xiaoqiang Ma, Yueyang Yu, Xubin Gu, Depeng Zhao
Summary: This study investigates the effect of intramolecular hydrogen bonds on the rotational barriers of axially chiral biaryl compounds. The experimental results show that compounds with hydrogen bonds have significantly lower rotational barriers. Theoretical studies reveal that intramolecular hydrogen bonds stabilize the transition state, reducing steric repulsion. This study provides important insights into the atropisomerization process of axially chiral biaryl compounds.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Clinical Neurology
Andrea Cippitelli, Gilles Zribi, Lawrence Toll
Summary: PPL-103 has shown potential as a pharmacotherapy for the treatment of cocaine use disorder (CUD). It reduces self-administration of cocaine, decreases motivation for cocaine, and attenuates binge-like cocaine taking. PPL-103 also reduces priming- and cue-induced reinstatement of cocaine seeking. Tolerance development was not observed with repeated PPL-103 treatment.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2022)
Article
Clinical Neurology
Neel Mehta, Neal E. Slatkin, Robert J. Israel, Nancy Stambler, Eric D. Shah
Summary: This study evaluated the safety and efficacy of methylnaltrexone in constipated patients and found that methylnaltrexone significantly improved rescue-free laxation. Abdominal pain was more common in patients receiving methylnaltrexone.
JOURNAL OF PAIN RESEARCH
(2023)
Article
Clinical Neurology
Bruce H. Chamberlain, Michelle Rhiner, Neal E. Slatkin, Nancy Stambler, Robert J. Israel
Summary: This study found that Methylnaltrexone (MNTX) is an effective treatment for opioid-induced constipation (OIC) in both cancer and noncancer patients. After the first dose, MNTX rapidly induced a laxation response in the majority of patients, without compromising opioid-induced analgesia.
JOURNAL OF PAIN RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Neil Feeder, Elna Pidcock, Anthony M. Reilly, Ghazala Sadiq, Cheryl L. Doherty, Kevin R. Back, Paul Meenan, Robert Docherty
JOURNAL OF PHARMACY AND PHARMACOLOGY
(2015)
Meeting Abstract
Chemistry, Multidisciplinary
Ghazala Sadiq, Neil Feeder
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2015)
Article
Chemistry, Multidisciplinary
James McKenzie, Neil Feeder, Christopher A. Hunter
Meeting Abstract
Chemistry, Multidisciplinary
Neil Feeder
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2016)
Article
Chemistry, Medicinal
Patrick S. Johnson, Thomas Ryckmans, Justin Bryans, Dave M. Beal, Kevin N. Dack, Neil Feeder, Anthony Harrison, Mark Lewis, Helen J. Mason, James Mills, Julie Newman, Christelle Pasquinet, Dave J. Rawson, Lee R. Roberts, Rachel Russell, Deborah Spark, Alan Stobie, Toby J. Underwood, Robin Ward, Simon Wheeler
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2011)
Article
Chemistry, Medicinal
Lyn H. Jones, Helen Baldock, Mark E. Bunnage, Jane Burrows, Nick Clarke, Michele Coghlan, David Entwistle, David Fairman, Neil Feeder, Craig Fulton, Laura Hilton, Kim James, Rhys M. Jones, Amy S. Kenyon, Stuart Marshall, Sandra D. Newman, Rachel Osborne, Sheena Patel, Matthew D. Selby, Emilio F. Stuart, Michael A. Trevethick, Karen N. Wright, David A. Price
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2011)
Article
Chemistry, Multidisciplinary
Peter T. A. Galek, Frank H. Allen, Laszlo Fabian, Neil Feeder
Article
Chemistry, Multidisciplinary
Peter A. Wood, Tjelvar S. G. Olsson, Jason C. Cole, Simon J. Cottrell, Neil Feeder, Peter T. A. Galek, Colin R. Groom, Elna Pidcock
Article
Chemistry, Inorganic & Nuclear
Birte Ahrens, Lionel P. Clarke, Neil Feeder, Muhammad S. Khan, Peiyi Li, James N. Martin, Paul R. Raithby
INORGANICA CHIMICA ACTA
(2008)
Article
Chemistry, Medicinal
Mark I. Lansdell, David Hepworth, Andrew Calabrese, Alan D. Brown, Julian Blagg, Denise J. Burring, Peter Wilson, David Fradet, T. Bruce Brown, Faye Quinton, Neela Mistry, Kim Tang, Natalie Mount, Peter Stacey, Nick Edmunds, Cathryn Adams, Samantha Gaboardi, Stevie Neal-Morgan, Chris Wayman, Susan Cole, Joanne Phipps, Mark Lewis, Hugh Verrier, Val Gillon, Neil Feeder, Anne Heatherington, Stefan Sultana, Scott Haughie, Steven W. Martin, Maria Sudworth, Sarah Tweedy
JOURNAL OF MEDICINAL CHEMISTRY
(2010)
Article
Chemistry, Medicinal
Paul A. Glossop, Charlotte A. L. Lane, David A. Price, Mark E. Bunnage, Russell A. Lewthwaite, Kim James, Alan D. Brown, Michael Yeadon, Christelle Perros-Huguet, Michael A. Trevethick, Nicholas P. Clarke, Robert Webster, Rhys M. Jones, Jane L. Burrows, Neil Feeder, Stefan C. J. Taylor, Fiona J. Spence
JOURNAL OF MEDICINAL CHEMISTRY
(2010)
Article
Chemistry, Medicinal
Paul A. Glossop, Christine A. L. Watson, David A. Price, Mark E. Bunnage, Donald S. Middleton, Anthony Wood, Kim James, Dannielle Roberts, Ross S. Strang, Michael Yeadon, Christelle Perros-Huguet, Nicholas P. Clarke, Michael A. Trevethick, Ian Machin, Emilio F. Stuart, Steven M. Evans, Anthony C. Harrison, David A. Fairman, Balaji Agoram, Jane L. Burrows, Neil Feeder, Craig K. Fulton, Barry R. Dillon, David A. Entwistle, Fiona J. Spence
JOURNAL OF MEDICINAL CHEMISTRY
(2011)
Article
Chemistry, Applied
Brian P. Chekal, Anthony M. Campeta, Yuriy A. Abramov, Neil Feeder, Paul P. Glynn, Robert W. McLaughlin, Paul A. Meenan, Robert A. Singer
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2009)
Article
Biochemistry & Molecular Biology
Laura Hilton, Rachel Osborne, Amy S. Kenyon, Helen Baldock, Mark E. Bunnage, Jane Burrows, Nick Clarke, Michele Coghlan, David Entwistle, David Fairman, Neil Feeder, Kim James, Rhys M. Jones, Nadia Laouar, Graham Lunn, Stuart Marshall, Sandra D. Newman, Sheena Patel, Matthew D. Selby, Fiona Spence, Emilio F. Stuart, Susan Sununerhill, Michael A. Trevethick, Karen N. Wright, Michael Yeadon, David A. Price, Lyn H. Jones
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)