Article
Multidisciplinary Sciences
Ben Cristofori-Armstrong, Elena Budusan, Lachlan D. Rash
Summary: The study compared the potency and mechanism of action of mambalgins on rat and human ASIC1 variants, revealing that mambalgin-3 weakly inhibits human ASIC1b under severe acidosis, but potentiates currents under mild/moderate acidosis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Xiao-Li Mao, Yi-Xuan Chen, Huan Yu, Quan-Wei Yang
Summary: Eugenol concentration-dependently inhibited ASIC currents in TG neurons in a non-competitive and G-protein independent manner, suggesting that ASICs could be a molecular target for eugenol in TG neurons. Eugenol also partly inhibited ASIC3 currents in CHO cells transfected with ASIC3. These findings contribute to a better understanding of the analgesic effect of eugenol in dental treatment.
NEUROSCIENCE LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Stefano Stabilini, Anna Menini, Simone Pifferi
Summary: TMEM16F is involved in various physiological processes and acts as both a Ca2+-dependent phospholipid scramblase and a Ca2+-activated ion channel. The ion selectivity of TMEM16F-mediated current depends on the recording configuration, with higher permeability for Na+ in inside-out experiments and a slight preference for Cl over bar permeation in whole-cell recordings.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sven Kuspiel, Dominik Wiemuth, Stefan Gruender
Summary: Research shows that the neuropeptide nocistatin does not directly activate ASIC1a channels, but rather indirectly activates them by acidifying the bath solution. This indicates the complexity of the regulatory mechanism of acid-sensing ion channels.
Article
Neurosciences
Shuang Wei, Ting-Ting Liu, Wang-Ping Hu, Chun-Yu Qiu
Summary: Resveratrol inhibits the electrophysiological activity and nociception mediated by acid-sensing ion channels (ASICs), providing a novel peripheral mechanism underlying its analgesic effect.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Multidisciplinary Sciences
Johann Biedermann, Sebastian Braunbeck, Andrew J. R. Plested, Han Sun
Summary: Fast excitatory synaptic transmission in the central nervous system relies on the AMPA-type glutamate receptor (AMPAR), which incorporates a nonselective cation channel. Recent studies combining molecular dynamic simulations and electrophysiology have revealed the ion permeation mechanisms of AMPA receptors, showing that Na+, K+, and Cs+ can permeate at physiological rates through a simple selectivity filter structure. The permissive architecture of the filter allows for rapid, nonselective cation permeation and copermeation by water, with Cs+ slightly more permeant than Na+ due to preferential binding sites.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Christian J. G. Tessier, Raymond M. Sturgeon, Johnathon R. Emlaw, Gregory D. McCluskey, F. Javier Perez-Areales, Corrie J. B. daCosta
Summary: Human adult muscle-type acetylcholine receptors are heteropentameric ion channels formed from different subunits, but they share a common ancestral homopentameric origin. A reconstructed ancestral muscle-type beta-subunit can form spontaneously open homopentameric ion channels, demonstrating that the function of the receptor is independent of agonist and does not require complex heteropentameric architecture.
Review
Biochemistry & Molecular Biology
Jasdip Singh Dulai, Ewan St John Smith, Taufiq Rahman
Summary: ASIC3, a member of the ENaC/DEG superfamily, is a channel protein that induces cellular current upon activation and persists in acidic conditions, encoding a nociceptive signal. It can be sensitized by certain mediators to lower proton concentrations, making it a potential target for analgesic development.
Article
Medicine, Research & Experimental
Rocio K. Finol-Urdaneta, Jeffrey R. McArthur, Ashraf Aboelela, Richard S. Bujaroski, Hiwa Majed, Alejandra Rangel, David J. Adams, Marie Ranson, Michael J. Kelso, Benjamin J. Buckley
Summary: Acid-sensing ion channels (ASICs) are transmembrane sensors of extracellular acidosis and potential drug targets. In this study, 6-iodoamiloride was identified as a potent inhibitor of ASIC1 and ASIC3, showing improved inhibitory activity compared to amiloride. This compound can be used to study the effects of ASIC inhibition on cell physiology.
MOLECULAR PHARMACEUTICS
(2023)
Article
Physiology
Daniel S. Matasic, Nicholas Holland, Mamta Gautam, David D. Gibbons, Nobuyoshi Kusama, Anne M. S. Harding, Viral S. Shah, Peter M. Snyder, Christopher J. Benson
Summary: This study revealed the determinants of paradoxical potentiation by amiloride on ASIC3 channels, including modulation of pH-dependent activation and steady-state desensitization, as well as the mechanism mediated by specific residues. It further demonstrated the complex competitive interaction between amiloride, Ca2+, and protons at potentially multiple sites in the channel.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Neurosciences
Miguel Salinas, Pascal Kessler, Dominique Douguet, Daad Sarraf, Nicolo Tonali, Robert Thai, Denis Servent, Eric Lingueglia
Summary: This study elucidated the inhibition mechanism of the snake venom toxin Mamb-1 on the acid-sensing ion channel ASIC1a through structure-activity relationship, molecular dynamics simulation, and experimental research. It provides important insights for further improvement and optimization of ASIC blockers.
Review
Neurosciences
Victoria S. Foster, Lachlan D. Rash, Glenn F. King, Michelle M. Rank
Summary: This review discusses the expression of ASICs in peripheral and CNS-resident immune cells, and how their activation during pathological tissue acidosis can affect immune cell function, modulating inflammatory pathology in the CNS. It also highlights the importance of understanding the contribution of ASICs to immune cell function in neuropathology for potential therapeutic benefits.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Cell Biology
Gregory C. Amberg, Ji Yeon Lee, Sang Don Koh, Kenton M. Sanders
Summary: A-type currents, rapidly inactivating voltage-gated potassium currents, were identified in smooth muscle cells (SMCs) isolated from murine fundus, with robust peak amplitudes averaging 1.5 nA at 0 mV. These currents are likely active at physiological membrane potentials and contribute to the negative membrane potentials of this tonic smooth muscle. Kv4 channels are likely responsible for generating the A-type current in murine fundus SMCs, as confirmed by quantitative analysis and immunohistochemistry.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yevheniia Kravenska, Vanessa Checchetto, Ildiko Szabo
Summary: Potassium ions can enter and exit mitochondria through various channels in the outer and inner membranes, with the ATP-dependent potassium channel being the most studied and playing a crucial role in protecting cells against ischemic and neuronal damage.
Article
Parasitology
Evgeny G. Chulkov, Elena Isaeva, Cheryl L. Stucky, Jonathan S. Marchant
Summary: The parasitic flatworm ion channel, TRPMPZQ, is activated by praziquantel (PZQ) and membrane stretch, making it a multimodal ion channel. Conservation of TRPMPZQ suggests its importance in flatworm physiology. The mechanosensitivity of TRPMPZQ is significant for schistosome physiology due to recurring pressures and mechanical cues.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2023)
Article
Chemistry, Medicinal
Melissa Egbertson, Georgia B. McGaughey, Steven M. Pitzenberger, Shaun R. Stauffer, Craig A. Coburn, Shawn J. Stachel, Wenjin Yang, James C. Barrow, Lou Anne Neilson, Melody McWherter, Debra Perlow, Bruce Fahr, Sanjeev Munshi, Timothy J. Allison, Katharine Holloway, Harold G. Selnick, ZhiQiang Yang, John Swestock, Adam J. Simon, Sethu Sankaranarayanan, Dennis Colussi, Katherine Tugusheva, Ming-Tain Lai, Beth Pietrak, Shari Haugabook, Lixia Jin, I-W. Chen, Marie Holahan, Maria Stranieri-Michener, Jacquelynn J. Cook, Joseph Vacca, Samuel L. Graham
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2015)
Article
Chemistry, Medicinal
William D. Shipe, Steven S. Sharik, James C. Barrow, Georgia B. McGaughey, Cory R. Theberge, Jason M. Uslaner, Youwei Yan, John J. Renger, Sean M. Smith, Paul J. Coleman, Christopher D. Cox
JOURNAL OF MEDICINAL CHEMISTRY
(2015)
Article
Multidisciplinary Sciences
Feng Rao, Jing Xu, Chenglai Fu, Jiyoung Y. Cha, Moataz M. Gadalla, Risheng Xu, James C. Barrow, Solomon H. Snyder
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2015)
Article
Chemistry, Medicinal
Scott T. Harrison, Michael S. Poslusney, James J. Mulhearn, Zhijian Zhao, Nathan R. Kett, Jeffrey W. Schubert, Jeffrey Y. Melamed, Timothy J. Allison, Sangita B. Patel, John M. Sanders, Sujata Sharma, Robert F. Smith, Dawn L. Hall, Ronald G. Robinson, Nancy A. Sachs, Pete H. Hutson, Scott E. Wolkenberg, James C. Barrow
ACS MEDICINAL CHEMISTRY LETTERS
(2015)
Review
Biochemistry & Molecular Biology
Nicholas E. Calcaterra, James C. Barrow
ACS CHEMICAL NEUROSCIENCE
(2014)
Article
Chemistry, Medicinal
Laureen Colis, Glen Ernst, Sara Sanders, Hester Liu, Paul Sirajuddin, Karita Peltonen, Michael DePasquale, James C. Barrow, Marikki Laiho
JOURNAL OF MEDICINAL CHEMISTRY
(2014)
Article
Biochemistry & Molecular Biology
Feng Rao, Jiyoung Cha, Jing Xu, Risheng Xu, M. Scott Vandiver, Richa Tyagi, Robert Tokhunts, Michael A. Koldobskiy, Chenglai Fu, Roxanne Barrow, Mingxuan Wu, Dorothea Fiedler, James C. Barrow, Solomon H. Snyder
Article
Neurosciences
Jason M. Uslaner, Sean M. Smith, Sarah L. Huszar, Rashida Pachmerhiwala, Richard M. Hinchliffe, Joshua D. Vardigan, Shannon J. Nguyen, Nathan O. Surles, Lihang Yao, James C. Barrow, Victor N. Uebele, John J. Renger, Janet Clark, Pete H. Hutson
Article
Oncology
Laureen Colis, Karita Peltonen, Paul Sirajuddin, Hester Liu, Sara Sanders, Glen Ernst, James C. Barrow, Marikki Laiho
Editorial Material
Chemistry, Medicinal
James C. Barrow
ACS MEDICINAL CHEMISTRY LETTERS
(2019)
Article
Chemistry, Medicinal
Michael M. Wormald, Glen Ernst, Huijun Wei, James C. Barrow
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2019)
Article
Pharmacology & Pharmacy
Yupin Su, Michael DePasquale, Gangling Liao, Ingrid Buchler, Gongliang Zhang, Spencer Byers, Gregory V. Carr, James Barrow, Huijun Wei
Summary: Selective inhibition of MBCOMT has shown promise in blocking dopamine metabolism, potentially improving cognitive deficits in disorders such as schizophrenia, ADHD, and traumatic brain injury.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Editorial Material
Chemistry, Medicinal
Craig W. Lindsley, James Barrow, Kelly Chibale, Maria Laura Bolognesi, Stuart Conway, William Denny, Ke Ding, Stefan Laufer, Luhua Lai, Hong Liu, Nouri Neamati, Takayoshi Suzuki, Nicholas Meanwell, Wendy Young
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Editorial Material
Chemistry, Medicinal
James C. Barrow, Craig W. Lindsey
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Sandip Mukherjee, Molee Chakraborty, Jake Haubner, Glen Ernst, Michael DePasquale, Danielle Carpenter, James C. Barrow, Anutosh Chakraborty
Summary: Obesity and nonalcoholic fatty liver disease (NAFLD) are global health concerns. LI-2242, an inhibitor of the inositol pyrophosphate pathway, shows potential therapeutic effects in obesity and NAFLD by reducing body weight, improving glycemic parameters, and ameliorating hepatic steatosis. LI-2242 also enhances mitochondrial oxygen consumption rate and insulin signaling in adipocytes and hepatocytes in vitro.
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)
