Article
Oncology
Chan-Chuan Liu, Cheng-Lin Wu, I-Chun Yeh, Sheng-Nan Wu, Chun- Sze, Po-Wu Gean
Summary: Continuous irradiation-induced resistance (CIIR) in GBM leads to TGF-beta secretion, activation of pro-survival Akt, downregulation of p21 independent of p53, upregulation of multi-drug resistant proteins, enhanced cell mobility and proliferation. CIIR also diminishes BK channel activity in an expression-independent manner. Cilostazol, a phosphodiesterase-3 inhibitor, can reverse CIIR-induced BK channel inactivation, potentially serving as a repurposed treatment for GBM.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Biology
David B. Halling, Ashley E. Philpo, Richard W. Aldrich, Jon T. Sack
Summary: The activation of KCa2.1-3 calcium-activated potassium channels (SK) requires the interaction of both the N-terminal domain and C-terminal domain of calmodulin. The binding affinity between the N-terminal domain and SK peptide is stronger in the presence of calcium, while the binding affinity of the C-terminal domain is calcium-independent. The calcium-dependent associations of both domains of calmodulin to the SK peptide are crucial events during the gating process.
Article
Clinical Neurology
Anqi Wang, Yujia Zhou, Huangying Chen, Jiawei Jin, Yingqi Mao, Shuiliang Tao, Tao Qiu
Summary: This study investigated the impact of small-conductance calcium-activated potassium channels (SK channels) on the dopaminergic neuron pathways in the ventral tegmental area (VTA) during post-stroke depression (PSD) and found that inhibiting the SK channels can improve depression symptoms. The results of this study provide new insights into the pathogenesis of PSD and the possibility of developing new strategies to prevent PSD by targeting SK channels.
NEUROPSYCHIATRIC DISEASE AND TREATMENT
(2023)
Article
Biology
Chiara Celotto, Carlos Sanchez, Konstantinos A. Mountris, Pablo Laguna, Esther Pueyo
Summary: Hyperactivity of the parasympathetic nervous system increases the risk of paroxysmal atrial fibrillation. Acetylcholine, the parasympathetic neurotransmitter, shortens action potential duration and increases resting membrane potential, both of which contribute to the risk of reentry. Small-conductance calcium activated potassium (SK) channels are potential targets for treating atrial fibrillation. This study explores the effects of SK channel block and beta-adrenergic stimulation on countering cholinergic activity in human atrial cell and tissue models. It finds that SK channel block alone can prolong action potential duration and stop sustained rotors, while beta-adrenergic stimulation terminates rotors but has variable outcomes depending on baseline action potential morphology. The combination of SK channel block and beta-adrenergic stimulation shows promising anti-arrhythmic potential.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Immunology
Janne Bredehoeft, Amalia M. Dolga, Birgit Honrath, Sybille Wache, Sybille Mazurek, Carsten Culmsee, Regien G. Schoemaker, Rudiger Gerstberger, Joachim Roth, Christoph Rummel
Summary: The study found that while CyPPA can induce short-term hyperthermia by altering metabolic pathways, its anti-inflammatory effects during severe LPS-induced systemic inflammation are limited.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Anna M. Olszewska, Adam K. Sieradzan, Piotr Bednarczyk, Adam Szewczyk, Michal A. Zmijewski
Summary: The study reveals that calcitriol can directly affect the activity of the mitochondrial potassium channel in human astrocytoma cells, suggesting its potential role in regulating mitochondrial function.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2022)
Article
Multidisciplinary Sciences
Bing Feng, Hesong Liu, Ila Mishra, Clemens Duerrschmid, Peiyu Gao, Pingwen Xu, Chunmei Wang, Yanlin He
Summary: Asprosin, a recently discovered adipokine, activates AgRP neurons in the ARH through binding to Ptprd, and the SK channel plays a crucial role in mediating this effect. Deficiency or elevation of circulating asprosin affects the SK current in AgRPARH neurons, and deletion of SK3 blocks asprosin-induced activation of AgRPARH neurons and overeating.
Review
Neurosciences
Marcos Fabio DosSantos, Lionete Gall Acosta Acosta Filha, Carla Pires Verissimo, Carolina Kaminski Sanz, Parisa Gazerani
Summary: Potassium (K+) channels maintain the resting potential of living cells and can be regulated by voltage and potassium gradients. In addition, small-conductance calcium activated potassium (SK) channels can translate changes in intracellular calcium levels into changes in membrane potassium conductance and resting membrane potential. This review article discusses the structure, presence, distribution, function, pharmacological modulation, and role of SK channels in health and disease, with a focus on nociception and pain.
JOURNAL OF INTEGRATIVE NEUROSCIENCE
(2023)
Article
Chemistry, Physical
Przemyslaw Borys, Paulina Trybek, Beata Dworakowska, Piotr Bednarczyk, Agata Wawrzkiewicz-Jalowiecka
Summary: The patch-clamp technique is a powerful tool for real-time observation of transport protein activity; the proposed simplified mathematical method in this study can assess distinct conformational substates of the channel.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biochemistry & Molecular Biology
Shunsuke Ando, Hiroya Mizutani, Makoto Muramatsu, Yumiko Hagihara, Hiroki Mishima, Rubii Kondo, Yoshiaki Suzuki, Yuji Imaizumi, Hisao Yamamura
Summary: This study investigates the role of SKCa and IKCa channels in regulating spontaneous Ca2+ oscillations in rat pinealocytes. The results show that SKCa channels, but not IKCa channels, contribute to the amplitude and frequency of spontaneous Ca2+ oscillations. The activity of SKCa2 channels plays a crucial role in controlling cytosolic Ca2+ signaling and melatonin production in the pineal gland.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Saoussen Mlayah-Bellalouna, Dorra Aissaoui-Zid, Aurelie Chantome, Jed Jebali, Soumaya Souid, Emna Ayedi, Hafedh Mejdoub, Maya Belghazi, Naziha Marrakchi, Khadija Essafi-Benkhadir, Christophe Vandier, Najet Srairi-Abid
Summary: The concept of using small conductance Ca2+-activated potassium channels (SKCa) as a pharmacological target for cancer treatment has gained increasing attention in recent years. In this study, researchers isolated the P01 toxin from Androctonus australis (Aa) scorpion venom and investigated its effects on glioblastoma U87, breast MDA-MB231, and colon adenocarcinoma LS174 cancer cell lines. The results showed that P01 specifically inhibited the proliferation, adhesion, and migration of U87 glioblastoma cells, with IC50 values in the micromolar range. Furthermore, P01 was found to reduce the currents recorded in HEK293 cells expressing SK2 channels, but had no effect on cells expressing SK3 channels. This study highlights the potential of scorpion peptides in understanding the role of SKCa channels in tumorigenesis and developing targeted therapeutic molecules for glioblastoma.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Neurosciences
Mina G. Nashed, Shannon Waye, S. M. Nageeb Hasan, Diana Nguyen, Micaela Wiseman, Jing Zhang, Harry Lau, O. Chandani Dinesh, Roger Raymond, Iain R. Greig, Francis Rodriguez Bambico, Jose N. Nobrega
Summary: This study found that the SK channel is impaired in the chronic unpredictable stress model, which is associated with the pathophysiology of depressive disorders. Inhibition of SK3 channels can alleviate depressive-like behavior without affecting general locomotor activity.
PSYCHOPHARMACOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Masayuki Takahashi, Hisashi Yokoshiki, Hirofumi Mitsuyama, Masaya Watanabe, Taro Temma, Rui Kamada, Hikaru Hagiwara, Yumi Takahashi, Toshihisa Anzai
Summary: The study demonstrates that the blocker apamin, which targets small-conductance Ca2+-activated K+ channels, has anti-arrhythmic effects by improving action potential duration shortening and calcium handling abnormalities in ventricular myocardium. This effect is likely attributed to the reduction of Ca-i/V-m uncoupling.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Paolo Zuccolini, Loretta Ferrera, Alessia Remigante, Cristiana Picco, Raffaella Barbieri, Sara Bertelli, Oscar Moran, Paola Gavazzo, Michael Pusch
Summary: This research investigated the effect of DCPIB on pancreatic duct adenocarcinoma (PDAC) and melanoma and found that DCPIB directly targeted BK channels and increased intracellular Ca2+ levels. These findings are important for the development of DCPIB-based modulators of ion channels and membrane proteins in the future.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Ricardo Gomez, Laura E. Maglio, Alberto J. Gonzalez-Hernandez, Belinda Rivero-Perez, David Bartolome-Martin, Teresa Giraldez
Summary: Postsynaptic NMDARs play a crucial role in synaptic plasticity by acting as coincidence detectors, but their function can be fine-tuned by various postsynaptic signaling proteins. BK channels have been found to suppress NMDAR activation by inducing negative feedback inhibition through K+ efflux. Neurons with NMDAR-BK coupling function as high-pass filters, preventing the induction of spike timing-dependent plasticity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Eduard Badarau, Zhuo Wang, Dan L. Rathbone, Andrea Costanzi, Thomas Thibault, Colin E. Murdoch, Said El Alaoui, Milda Bartkeviciute, Martin Griffin
CHEMISTRY & BIOLOGY
(2015)
Article
Chemistry, Medicinal
Sebastien Dilly, Jean-Francois Liegeois
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2016)
Article
Chemistry, Organic
Francois Munyemana, Isabelle George, Alain Devos, Alain Colens, Eduard Badarau, Anne-Marie Frisque-Hesbain, Aurore Loudet, Edmond Differding, Jean-Marie Damien, Jeanine Remion, Jacqueline Van Uytbergen, Leon Ghosez
Article
Chemistry, Medicinal
Thomas Drapier, Pierre Geubelle, Charlotte Bouckaer, Lise Nielsen, Saara Laulumaa, Eric Goffin, Sebastien Dilly, Pierre Francotte, Julien Hanson, Lionel Pochet, Jette Samm Kastrup, Bernard Pirotte
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Sebastien Dilly, Aurelien Fotso Fotso, Nathalie Lejal, Gloria Zedda, Mohamad Chebbo, Fryad Rahman, Simon Companys, Helene C. Bertrand, Jasmina Vidic, Magali Noiray, Marie-Christine Alessi, Bogdan Tarus, Stephane Quideau, Beatrice Riteau, Anny Slama-Schwok
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Organic
Eduard Badarau, Frederic Robert, Stephane Massip, Florian Jakob, Simon Lucas, Sven Frormann, Leon Ghosez
Article
Chemistry, Medicinal
Eduard Badarau, Frederic Robert, Stephane Massip, Florian Jakob, Simon Lucas, Daniela Friebe, Stephanie Hennen, Sven Frormann, Leon Ghosez
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Multidisciplinary
Eduard Badarau, Franck Suzenet, Adriana-Luminita Finaru, Gerald Guillaumet
STUDIA UNIVERSITATIS BABES-BOLYAI CHEMIA
(2019)
Article
Chemistry, Medicinal
Sebastien Dilly, Melanie Garnier, Marion Sole, Remi Bailly, Nada Taib, Isabelle Bestel
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2020)
Article
Biochemistry & Molecular Biology
Sebastien Dilly, Linda J. Roman, Nicolas Bogliotti, Juan Xie, Eric Deprez, Anny Slama-Schwok
Article
Chemistry, Multidisciplinary
Eduard Badarau, K. Harsha Vardhan Reddy, Aurore Loudet, Charles Simon, Laurent Trembleau, Stijn Claerhout, Etienne Pair, Stephane Massip, Philippe Breton, Brigitte Lesur, Solo Goldstein, Jean-Marie Fourquez, Jean Michel Henlin, Leon Ghosez
CHEMISTRY-A EUROPEAN JOURNAL
(2020)
Article
Biochemical Research Methods
Jonathan Ribes, Nataliia Beztsinna, Remy Bailly, Sabine Castano, Estelle Rascol, Nada Taib-Maamar, Eduard Badarau, Isabelle Bestel
Summary: Natural photosensitizers, like flavins, have excellent toxicity profiles and activating energy ranges compatible with biological systems. Flavin-rich nanoparticles show promise in photodynamic therapies and drug delivery with their improved pharmacokinetics and reduced photobleaching. The design of riboflavin-rich nanoparticles with tunable morphology and predictable self-assembly can be guided by coarse-grained simulations of the self-assembling process.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jonathan Ribes, Pauline Cossard, Khaled Al Yaman, Isabelle Bestel, Eduard Badarau
Summary: Due to their ability to absorb light and generate reactive species, photosensitizers have become promising tools in various physicochemical and biological processes. Natural photosensitizers, such as porphyrins and flavins, have shown their effectiveness as photodynamic therapeutics. This article presents a reliable method to characterize the photosensitizing activity of flavins, using parameters such as blue LED light source, pH mimicking the tumor environment, and tetrazolium dye to monitor the efficacy. The method can be used to rank flavins based on their photosensitizing activities, which is important for discovering potent photosensitizers for photodynamic therapy.
Article
Biochemistry & Molecular Biology
Jonathan Ribes, Yann Bourdeau, Estelle Rascol, Isabelle Bestel, Eduard Badarau
Summary: The structure-photosensitizing activity relationships for a series of flavin analogues were investigated in this study. The introduction of halogen atoms in the C7- and/or C8-positions on the isoalloxazine ring was the main modification. The results showed that the photosensitizing activity increased with the size of the halogen atoms, and the 7-haloisoalloxazines presented a better cellular toxicity profile compared to the 8-substituted analogues.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Pierre Geubelle, Julie Gilissen, Sebastien Dilly, Laurence Poma, Nadine Dupuis, Celine Laschet, Dayana Abboud, Asuka Inoue, Francois Jouret, Bernard Pirotte, Julien Hanson
BRITISH JOURNAL OF PHARMACOLOGY
(2017)
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)
