Review
Biochemistry & Molecular Biology
Xin Wu, Liang Hong
Summary: Calmodulin (CaM) is a small protein that serves as a ubiquitous signal transducer, regulating neuronal plasticity, muscle contraction, and immune response. It interacts with ion channels and plays regulatory roles in cellular electrophysiology. Mutations in CaM-binding IQ domain can lead to various diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Altin Sula, David Hollingworth, Leo C. T. Ng, Megan Larmore, Paul G. DeCaen, B. A. Wallace
Summary: This study identified a previously unidentified receptor site within the NavMs voltage-gated sodium channel, where tamoxifen and its metabolic products bind, inhibiting sodium conductance and potentially leading to the development of new drugs for sodium channelopathies.
Article
Multidisciplinary Sciences
Shuo Han, Xiang-Ping Chu, Ryan Goodson, Prae Gamel, Sophia Peng, Joshua Vance, Shizhen Wang
Summary: Cholesterol inhibits the hHv1 channel by stabilizing the voltage-sensing S4 segment at resting conformations, providing a mechanism for the regulation of fertilization by the hHv1 channel.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Yong Ai, Xudong Zhang, Xudong Hu, Jinte Gao, Jiyuan Liu, Shaowu Ou, Jun Wang
Summary: This study found that Nav1.6 expression is significantly upregulated in glioma and is positively correlated with pathological grade. Inhibition of Nav1.6 reduces proliferation, migration, and invasion of glioma cells and increases apoptosis. Furthermore, several FDA-approved drugs highly correlated with Nav1.6 were identified as potential therapeutic options for patients with glioma through virtual screening and drug sensitivity analysis.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Sigrid Noreng, Tianbo Li, Jian Payandeh
Summary: Voltage-gated sodium channels play crucial roles in physiological processes, and recent breakthroughs in cryo-electron microscopy have advanced our understanding of their structure and pharmacological action. This provides new insights for the design of drugs targeting Na channels.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Daohua Jiang, Jiangtao Zhang, Zhanyi Xia
Summary: Voltage-gated sodium channels are crucial for the rapid rising-phase of action potentials, and their mutations can lead to various human diseases. Recent studies using cryo-EM structures have provided valuable insights into the mechanism of eukaryotic Na-V channels, offering templates for drug development.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Chemistry, Medicinal
James R. Groome
Summary: This article reviews the study of marine toxins, particularly on their actions on sodium ion channels regulated by transmembrane voltage and neurotransmitters. The focus is on the diverse conotoxin peptides and their potential applications in evolutionary relationships, biological actions, disease therapy, and understanding the structure of ion channels at the atomic level.
Article
Chemistry, Medicinal
Nace Zidar, Tihomir Tomasic, Danijel Kikelj, Martina Durcik, Jan Tytgat, Steve Peigneur, Marc Rogers, Alexander Haworth, Robert W. Kirby
Summary: Voltage-gated sodium channels (Navs) play a crucial role in neurotransmission and their dysfunction is associated with various neurological disorders. In this study, a new series of aryl and acylsulfonamides were discovered as state-dependent inhibitors of Nav1.3 channels. These compounds displayed strong selective activity against the inactivated state of the Nav1.3 channel, with weaker activity against Nav1.5 and Nav1.7 channels. These findings provide a valuable tool for further evaluation of Nav1.3 channel as a potential drug target.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Phuong T. Nguyen, Vladimir Yarov-Yarovoy
Summary: This review focuses on recent progress, current challenges, and future opportunities in developing sodium channel targeting small molecules and peptides as non-addictive therapeutics for treating pain.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Scott P. Fraser, Rustem Onkal, Margaux Theys, Frank Bosmans, Mustafa B. A. Djamgoz
Summary: The neonatal splice variant of Na(V)1.5 (nNa(V)1.5) in breast and colon cancer cells can be pharmacologically distinguished from the adult counterpart (aNa(V)1.5) by specific antibodies and toxins. This finding may contribute to the development of low molecular weight compounds as non-toxic therapeutic drugs for cancers expressing nNa(V)1.5.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Physiology
Jamie S. S. Lindner, Salil R. R. Rajayer, Briana J. J. Martiszus, Stephen M. M. Smith
Summary: The calcium-sensing receptor agonist, cinacalcet, regulates neuronal excitability by modulating the voltage-dependence of voltage-gated sodium channel (VGSC) currents. This regulation is achieved by shifting the voltage-dependence of VGSC currents and involves an unidentified inhibitory molecule that is G-protein dependent.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Eva Fuchs, David Alexander Christian Messerer, Georg Karpel-Massler, Michael Fauler, Thomas Zimmer, Bettina Jungwirth, Karl Josef Foehr
Summary: In addition to its classical anti-cancer activity, the tumor therapeutic drug TIC10 may enhance its anti-tumor properties by blocking voltage-gated sodium channels.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Agronomy
Linlin Yuan, Kun Zhang, Zhenglei Wang, Limin Xian, Kaiyang Liu, Shaoying Wu
Summary: The sodium channel of Drosophila suzukii was cloned and found to have diverse gating properties and RNA editing.
PEST MANAGEMENT SCIENCE
(2023)
Article
Entomology
Haung Naw, Tuan Cuong Vo, Huong Giang Le, Jung-Mi Kang, Yi Yi Mya, Moe Kyaw Myint, Tong-Soo Kim, Ho-Joon Shin, Byoung-Kuk Na
Summary: This study identified high levels of kdr mutations in the Ae. aegypti population in the Mandalay area of Myanmar, suggesting widespread resistance to pyrethroid insecticides. The results underscore the need for an effective vector control program in Myanmar to address the increasing resistance in mosquitoes.
Article
Biochemistry & Molecular Biology
Quentin Coquerel, Claire Legendre, Jacinthe Frangieh, Stephan De Waard, Jerome Montnach, Leos Cmarko, Joseph Khoury, Charifat Said Hassane, Dimitri Breard, Benjamin Siegler, Ziad Fajloun, Harold De Pomyers, Kamel Mabrouk, Norbert Weiss, Daniel Henrion, Pascal Richomme, Cesar Mattei, Michel De Waard, Anne-Marie Le Ray, Christian Legros
Summary: This study screened and identified five new blockers of voltage-gated Na+ channels, with bebeerine showing promising therapeutic applications.
Review
Chemistry, Medicinal
Zan Toplak, Louise A. Hendrickx, Reham Abdelaziz, Xiaoyi Shi, Steve Peigneur, Tihomir Tomasic, Jan Tytgat, Lucija Peterlin-Masic, Luis A. Pardo
Summary: Research has shown the importance of ion channel expression in tumor progression, with Eag1 being overexpressed in many human tumors. However, finding selective inhibitors for Eag1 is challenging due to its structural similarities with the cardiac HERG channel. Structural differences between Eag1 and HERG channels may offer opportunities for selective targeting in cancer therapies.
MEDICINAL RESEARCH REVIEWS
(2022)
Article
Chemistry, Medicinal
Benedetta Girardi, Martina Manna, Sjors Van Klaveren, Tihomir Tomasic, Ziga Jakopin, Hakon Leffler, Ulf J. Nilsson, Daniel Ricklin, Janez Mravljak, Oliver Schwardt, Marko Anderluh
Summary: The study aimed to improve the affinity and target selectivity of a galectin-8 ligand by introducing modifications at positions 1 and 3 of the galactose, resulting in a promising lead for the development of new selective and potent ligands for galectin-8, highlighting its potential role in cell-based and in vivo studies.
Article
Chemistry, Medicinal
Sjors van Klaveren, Anders P. Sundin, Ziga Jakopin, Marko Anderluh, Hakon Leffler, Ulf J. Nilsson, Tihomir Tomasic
Summary: The study reports phthalazinone-galactals that show excellent selectivity for the galectin-8N-terminal domain, a protein prevalent in both pathology and tissue distribution. The dissected structure-activity relationships and extensive molecular dynamics meta-analysis accompany the discovery of these selective galectin-8N ligands, which will facilitate the study of galectin-8 biology and may have pharmaceutical relevance in a wide range of galectin-8 associated pathologies.
Article
Biochemistry & Molecular Biology
Bernarda Majc, Anamarija Habic, Metka Novak, Ana Rotter, Andrej Porcnik, Jernej Mlakar, Vera Zupunski, Ursa Pecar Fonovic, Damijan Knez, Nace Zidar, Stanislav Gobec, Janko Kos, Tamara Lah Turnsek, Anja Pislar, Barbara Breznik
Summary: This study found that cathepsin X is upregulated in human GBM tissues and localized in GBM cells, tumor-associated macrophages, and microglia. Selective cathepsin X inhibitors can decrease the viability of GBM cells and are colocalized with gamma-enolase, suggesting that cathepsin X is involved in GBM progression and could be a potential therapeutic target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
Anne-Sophie Depuydt, Steve Peigneur, Jan Tytgat
Summary: Pacemaker cells are crucial for the rhythm of the heart, and cardiovascular diseases and arrhythmias are major causes of hospital admissions and sudden death. The prevalence of arrhythmias will increase due to an aging population and risk factors. HCN channels, the molecular correlate of the pacemaker activity, have shown potential as targets for drug development to lower heart rate. However, there is still limited understanding of their pharmacology compared to other ion channels. Ivabradine is currently the only approved drug targeting HCN channels. This review focuses on the pacemaking process in the heart and summarizes current knowledge on HCN channels.
CURRENT CARDIOLOGY REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Aleksandra Kvetkina, Evgeny Pislyagin, Ekaterina Menchinskaya, Ekaterina Yurchenko, Rimma Kalina, Sergei Kozlovskiy, Leonid Kaluzhskiy, Alexander Menshov, Natalia Kim, Steve Peigneur, Jan Tytgat, Alexis Ivanov, Naira Ayvazyan, Elena Leychenko, Dmitry Aminin
Summary: This study investigated the neuroprotective effects of four peptides from sea anemones on Parkinson's disease. The peptides were found to inhibit PD inducers and reduce oxidative stress and inflammation. Furthermore, the study discovered that these peptides interact with the P2X7R channels, which are therapeutic targets for Parkinson's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Elena M. Loi, Tihomir Tomasic, Cyril Balsollier, Kevin van Eekelen, Matjaz Weiss, Martina Gobec, Matthew G. Alteen, David J. Vocadlo, Roland J. Pieters, Marko Anderluh
Summary: In this study, a novel OGT inhibitor with a uridine mimetic scaffold was identified through virtual screening. The inhibitor showed promising activity in enzyme assays and provides a potential starting point for the development of OGT inhibitors with clinical applications.
Article
Oncology
Spela Gubic, Louise Antonia Hendrickx, Xiaoyi Shi, Zan Toplak, Stefan Mozina, Kenny M. Van Theemsche, Ernesto Lopes Pinheiro-Junior, Steve Peigneur, Alain J. Labro, Luis A. Pardo, Jan Tytgat, Tihomir Tomasic, Lucija Peterlin Masic
Summary: In this article, a new class of potassium channel inhibitors is described, which selectively inhibits the K(V)1.3 channel and shows potential in inducing apoptosis and inhibiting cell proliferation. The K(V)1.3 channel has recently emerged as a target in cancer therapy. Through structural optimization, a novel K(V)1.3 inhibitor was designed and its potency and selectivity were investigated. The results showed that the new K(V)1.3 inhibitors effectively inhibited cancer cell proliferation and induced apoptosis.
Article
Biochemistry & Molecular Biology
Jessica Matos Kleiz-Ferreira, Hans Bernaerts, Ernesto Lopes Pinheiro-Junior, Steve Peigneur, Russolina Benedeta Zingali, Jan Tytgat
Summary: Coral snake venoms from the Micrurus genus are a diverse collection of components that act on multiple targets. They are mainly composed of phospholipases A(2) and three-finger toxins, which cause neuromuscular blockade. In addition to these major toxin families, minor components also play a significant role in the venom's overall activity. The venoms of five Micrurus species from Brazil were found to act on different types of targets, with potential potassium channel inhibitory activity being a key feature of their envenomation strategy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ziva Zajec, Jaka Dernovsek, Martina Gobec, Tihomir Tomasic
Summary: Hsp90 is a promising target for cancer treatment. The discovery of a novel class of Hsp90 CTD inhibitors through virtual screening provides new starting points for further development, showing enhanced antiproliferative activities in breast cancer and sarcoma cell lines.
Article
Chemistry, Multidisciplinary
Lucas J. Gutierrez, Marcela Vettorazzi, Jaka Dernovsek, Martina Durcik, Lucija Peterlin Masic, Tihomir Tomasic, Ricardo D. Enriz
Summary: In this study, we investigated the inhibitory activity of 4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine derivatives on bacterial DNA gyrase B (GyrB) through theoretical and experimental approaches. Our results revealed that QTAIM calculations can effectively quantify molecular interactions and determine the amino acids that interact with the ligands. Additionally, our simulations showed that this method can predict the affinity and potential activity of compounds that have not been synthesized.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Junyu Liu, Michael Maxwell, Thom Cuddihy, Theo Crawford, Madeline Bassetti, Cameron Hyde, Steve Peigneur, Jan Tytgat, Eivind A. B. Undheim, Mehdi Mobli
Summary: Receptor avidity through multivalency is difficult to engineer in synthetic molecules, but can be found in natural bivalent antibodies. The discovery of bivalent venom peptides with tandem repeat domains has provided insight into multivalency in biomolecules. ScrepYard, an online resource, assists in identifying SCREP sequences and characterizing this emerging class of biomolecules.
Article
Biochemistry & Molecular Biology
Anne-Sophie Depuydt, Piyush A. Patel, Zan Toplak, Chinmaya Bhat, Manuela Voracova, Irene Etelainen, Fiammetta Vitulano, Tanja Bruun, Antti Lempinen, Nives Hribernik, Eero Maki-Lohiluoma, Louise Hendrickx, Ernesto Lopes Pinheiro-Junior, Tihomir Tomasic, Lucija Peterlin Masic, Jari Yli-Kauhaluoma, Paula Kiuru, Jan Tytgat, Steve Peigneur
Summary: T-type calcium channels play important roles in cardiac function, and their dysfunction is associated with pathological conditions. In this study, a new class of T-type calcium channel inhibitors was discovered and their mechanism of action was investigated. These findings provide new insights into drug design and the interaction of drugs with T-type calcium channels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Sjors van Klaveren, Jaka Dernovsek, Ziga Jakopin, Marko Anderluh, Hakon Leffler, Ulf J. Nilsson, Tihomir Tomasic
Summary: Galectins are proteins that can bind to galactosides and play a crucial role in drug discovery. The authors have designed a series of aromatic 3-triazolyl-1-thiogalactosides and evaluated their binding affinities with different Galectins.