Archiv der Pharmazie最新文献

{"title":"Multitargeted Anticancer Activities: Cathepsin B–Carbonic Anhydrase IX/XII Inhibitors Show Enhanced Cytotoxicity Against Lung Adenocarcinoma Cells","authors":"Lalit Vats,&nbsp;Manishita Rani,&nbsp;Kiran Siwach,&nbsp;Kanika Sharma,&nbsp;Mettle Brahma,&nbsp;Yangala Sudheer Babu,&nbsp;Simone Giovannuzzi,&nbsp;Mulaka Maruthi,&nbsp;Neera Raghav,&nbsp;Claudiu T. Supuran,&nbsp;Pawan K. Sharma","doi":"10.1002/ardp.70337","DOIUrl":"10.1002/ardp.70337","url":null,"abstract":"<div>\u0000 \u0000 <p>The multi-target inhibition of two significant cancer drug targets, cathepsin B and human carbonic anhydrase (hCA) isoforms IX and XII has been explored. The exclusive synthesis of single isomeric structure of final compounds despite two possibilities, in vitro biological studies, in silico molecular docking, DFT and ADMET studies of a small library of 28 new benzenesulfonamides incorporating the 1,2,3-triazolylpyrazole motif are reported. The tumor-associated isoforms hCA IX and hCA XII have been remarkably inhibited in the low nanomolar range, while enzymatically important off-target isoforms hCA I and II were weakly inhibited by most of the synthesized sulfonamides. Overall, respectively, three (K_I &lt; 25 nM) and two compounds (K_I &lt; 5.7 nM) showed better inhibition of hCA IX and XII as compared with reference drug acetazolamide. Compound <b>9f</b> exhibited 35-fold and eightfold better hCA I/IX and hCA I/XII inhibition selectivity, respectively, as compared with SLC-0111. Likewise, all the synthesized compounds were also assayed for their inhibition profile against cathepsin B. Some compounds exhibited better inhibition of cathepsin B as compared with reference compound curcumin. In vitro cytotoxicity studies targeting non-cancerous Vero cells (green monkey kidney cells) and cancerous A549 cells (human lung adenocarcinoma cells) have also been performed, which showed interesting results.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149014966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Diterpenoids From Salvia rosmarinus Reveal a Compound With Antiproliferative and Antioxidant Activities","authors":"Diana Pérez-Juanchi,&nbsp;Celia Bustos-Brito,&nbsp;Ma. Teresa Ramírez-Apan,&nbsp;Antonio Nieto-Camacho,&nbsp;Leovigildo Quijano,&nbsp;Baldomero Esquivel","doi":"10.1002/ardp.70341","DOIUrl":"10.1002/ardp.70341","url":null,"abstract":"<p>Four previously undescribed diterpenoids (<b>1</b>–<b>4</b>) were isolated from the leaves of <i>Salvia rosmarinus</i> and characterized as 18-hydroxycarnosol (<b>1</b>), 18-acetoxyrosmanol (<b>2</b>), 18-acetoxycarnosol (<b>3</b>), and 18-acetoxy-7-<i>O</i>-methylrosmanol (<b>4</b>). Furthermore, nine known compounds, including carnosol (<b>5</b>), rosmanol (<b>6</b>), 7-<i>O</i>-methylacacetin (<b>7</b>), salvigenin (<b>8</b>), hispidulin (<b>9</b>), cirsimaritin (<b>10</b>), (1<i>S</i>,4<i>S</i>)-<i>p</i>-menth-2-ene-1,4-diol (<b>11</b>), 3,4,5-trimethoxycinnamyl alcohol (<b>12</b>), and vanillic acid (<b>13</b>) were also isolated. The structure of the new compounds was established primarily through the analysis of 1D and 2D nuclear magnetic resonance (NMR) experiments and high-resolution mass spectrometry by direct analysis in real time technique (HRMS DART). The absolute configuration of <b>1</b> and <b>2</b> was established by DP4+ analysis and comparison between experimental and theoretical electronic circular dichroism (ECD) spectra. The antiproliferative activity was evaluated against a panel of cancer cell lines and one normal cell line. Compounds <b>1</b> and <b>5</b> exhibited IC₅₀ values of 10.77 ± 1.4 and 10.19 ± 0.4 μM, respectively, against a leukemia cell line, K562, and 25.27 ± 2.5 and 37.40 ± 3.7 μM, respectively, against the noncancerous cell line COS-7. Compound <b>7</b> exhibited IC₅₀ values of 9.36 ± 0.1 μM against a glioblastoma cell line, U251, and 15.21 ± 1.7 μM against a prostate cell line, PC-3. The antioxidant activity of compound <b>1</b> was evaluated by its ability to scavenge the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the inhibition of lipid peroxidation by the Thiobarbituric Acid Reactive Substances assay (TBARS), with IC₅₀ of 25.50 ± 0.29 and 6.51 ± 0.09 μM, respectively. These results highlight the importance of <i>S. rosmarinus</i> being the subject of further chemical and biological studies.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13594988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking the Potential of Isatin Scaffolds in Acetylcholinesterase Inhibition","authors":"Toka Tharwat,&nbsp;Hala Bakr El-Nassan,&nbsp;Mina E. Adly,&nbsp;Mona M. Kamel","doi":"10.1002/ardp.70336","DOIUrl":"10.1002/ardp.70336","url":null,"abstract":"<div>\u0000 \u0000 <p>The therapeutic significance of acetylcholinesterase (AChE) inhibition is most prominently observed in the management of various neurodegenerative and neuromuscular disorders, including Alzheimer's disease (AD), and myasthenia gravis (MG). The present review examines isatin-based compounds as a promising class of drugs for treating these conditions, focusing on their ability to inhibit AChE. While AD is characterized by a significant loss of cholinergic neurons leading to a deficiency in acetylcholine (ACh), MG is an autoimmune disease where the body produces antibodies that block or destroy ACh receptors at the neuromuscular junction. By inhibiting AChE, therapeutic agents increase the availability of ACh, thereby enhancing cholinergic neurotransmission and improving muscle strength or cognitive function. The underlying issue in MG is the reduced number of functional receptors rather than a primary decrease in AChE production. However, inhibition of the enzyme remains a vital strategy for symptom management. Accordingly, this review provides a systematic overview of the various synthetic strategies reported in the literature over the last decade for enhancing isatin-based AChE inhibitory activity. These strategies include modifications of the isatin nitrogen, such as <i>N</i>-alkylation, <i>N</i>-acylation, or <i>N</i>-arylation. Another strategy is aromatic ring substitution, where various substituents (e.g., halogens, nitro, amino, and alkyl groups) are introduced typically at the C₅, C₆, and/or C₇ positions. C₃-carbonyl functionalization is also reported, exemplified by the formation of Schiff bases, hydrazones, or spirocyclic derivatives. Our findings highlight the exceptional potential and adaptability of isatin derivatives in medicinal chemistry, highlighting the major advances within the last 10 years and the future directions.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Identification to Enzymatic Activity Profiling: Comprehensive Characterization of BloCAβ, a Probiotic β-Carbonic Anhydrase From Bifidobacterium longum","authors":"Simone Giovannuzzi,&nbsp;Andrea Ammara,&nbsp;Simone Carradori,&nbsp;Viviana De Luca,&nbsp;Marialucia Gallorini,&nbsp;Damiano Iacovozzi,&nbsp;Amelia Cataldi,&nbsp;Ilaria D'Agostino,&nbsp;Davide Moi,&nbsp;Valentina Onnis,&nbsp;Claudiu T. Supuran,&nbsp;Clemente Capasso","doi":"10.1002/ardp.70333","DOIUrl":"10.1002/ardp.70333","url":null,"abstract":"<p>The microbiota comprises communities of microorganisms that establish complex relationships with the host and play key roles in physiology, metabolism, and immunity. Increasing evidence highlights microbiota alterations in several diseases, particularly those driven by oxidative stress-induced inflammation. Thus, identifying probiotic enzymes implicated in essential metabolic pathways is highly relevant to the development of future strategies targeting dysbiosis and related diseases. Herein, we report the first biochemical characterization of β-class carbonic anhydrase (CA) from <i>Bifidobacterium longum</i> (BloCAβ) by inhibition and activation profiles. The enzyme was recombinantly expressed, purified, and kinetically characterized, displaying a catalytic efficiency within the same order of magnitude as, although lower than, that of human (h)CA I. The functional profile of this novel CA was explored using a panel of commercial sulfonamides, sulfamides, sulfamates, and inorganic/organic anions as inhibitors. Furthermore, several biogenic amines and amino acids were assessed as potential activators of BloCAβ, and their activation profiles were compared with those of hCAs I and II. The cellular effects of selected BloCAβ activators was further evaluated in human macrophages under basal and proinflammatory conditions, while the safety profile was assessed in human intestinal epithelial cells (HIECs). Among them, serotonin (<b>38</b>) was found to significantly enhance cell metabolic activity in both conditions and preserve the metabolic activity of HIECs, further supporting its biocompatibility. Overall, these results provide the first biochemical and functional characterization of BloCAβ and establish a biochemical basis for future studies investigating the physiological role of probiotic CAs in bacterial models.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Ultra-Fast UPLC-MS/MS Method for Quantifying Ivosidenib: Application to Assessment of Metabolic Stability in Human Liver Microsomes","authors":"Mohamed W. Attwa,&nbsp;Ali S. Abdelhameed,&nbsp;Haitham AlRabiah,&nbsp;Adnan A. Kadi","doi":"10.1002/ardp.70331","DOIUrl":"10.1002/ardp.70331","url":null,"abstract":"<div>\u0000 \u0000 <p>Ivosidenib (Tibsovo) is a groundbreaking, first-in-class medication that specifically and reversibly blocks isocitrate dehydrogenase (IDH1), earning multiple FDA approvals for cancers harboring IDH1 mutations. This research developed a rapid, dependable, and sensitive UPLC-MS/MS technique to assess the metabolic stability of ivosidenib (IVB) in human liver microsomes (HLM). The method showed a commendable environmental profile (ComplexMoGAPI score: 69.0, AGREEprep: 0.68, and AGSA: 72.22). Using StarDrop software (including DEREK and P450 tools), chemical structure alerts were detected, and in silico analysis of metabolic vulnerability (CSL value) was conducted. A straightforward isocratic mobile phase system with a stationary phase (C8 column) efficiently separated IVB and baricitinib (BCB as internal standard) in an ultra-fast 1-min run at 0.4 ml/min flow rate. The IVB calibration curve showed a linearity over the range 1.0 to 4000 ng/ml. Accuracy and precision during intra- and inter-day assessments in the range of −2.18% to 10.17% and −2.83% to 12.50%, respectively. The current approach uniquely combines HLMs-based metabolic stability assessment with in silico predictions of metabolic soft spots, toxicity, and ADME, along with dual greenness evaluation, all within a single workflow. The in vitro half-life (<i>t</i>_1/2) of IVB was approximately 44.89 min, with an intrinsic clearance (Cl_int) of 18.06 ml/min/kg. In silico analysis suggests that IVB derivatives with modifications to the 5-fluoro-3-pyridine group (75% at C21) and the 4-cyano-2-pyridine group (23% at C36) may exhibit varying metabolic stability, warranting further experimental validation.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Chromene Derivatives as Promising VEGFR-2 Inhibitors: Experimental Cytotoxicity and Comprehensive Computational Characterization","authors":"Hazem Elkady,&nbsp;Aisha A. Alsfouk,&nbsp;Eslam B. Elkaeed,&nbsp;Walid E. Elgammal,&nbsp;Hazem A. Mahdy,&nbsp;Ahmed Nofal,&nbsp;Ibrahim H. Eissa,&nbsp;Dalal Z. Husein,&nbsp;Fatma G. Amin,&nbsp;Ahmed M. Metwaly","doi":"10.1002/ardp.70328","DOIUrl":"10.1002/ardp.70328","url":null,"abstract":"<div>\u0000 \u0000 <p>A new series of chromene derivatives (<b>12–19</b>) was rationally designed as potential inhibitors of vascular endothelial growth factor receptor-2 (VEGFR-2) by integrating essential pharmacophoric and structural features. The target compounds were synthesized and structurally confirmed using spectroscopic techniques. Their in vitro antiproliferative activities were evaluated against a panel of human cancer cell lines (MCF-7, MDA-MB-231, HepG-2, and HCT-116) alongside normal human cells (WI-38 and WISH), in addition to a VEGFR-2 enzyme inhibition assay. Among the synthesized derivatives, compound <b>17</b> emerged as the most potent candidate, displaying low micromolar IC₅₀ values across all tested cancer cell lines and superior VEGFR-2 inhibitory activity (IC₅₀ = 0.518 µM) compared with the reference drug sorafenib (IC₅₀ = 0.809 µM). Mechanistic investigations revealed that compound <b>17</b> induced pronounced cell cycle arrest and triggered apoptosis, as demonstrated by Annexin V–FITC/PI flow cytometric analysis. Computationally, Density Functional Theory (DFT) calculations demonstrated favorable electronic properties for compound <b>17,</b> supporting effective ligand–receptor interactions. Molecular docking and 100-ns molecular dynamics (MD) simulations, complemented by MM-GBSA binding free energy calculations, Protein–Ligand Interaction Fingerprinting (Pro-LIF), Principal Component Analysis (PCA-T), and Free Energy Landscape (FEL) analyses, confirmed the stability and favorable binding energetics of compound <b>17</b> within the VEGFR-2 active site. Furthermore, in silico ADME–Tox profiling predicted acceptable pharmacokinetic behavior and a favorable safety profile. Collectively, these experimental and computational findings identify compound <b>17</b> as a promising and mechanistically well-characterized VEGFR-2 inhibitor, warranting further in vivo investigation.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Activation-Dependent Anti-Liver Cancer Activity and Organ-Specific Toxicity of Retrorsine From Fanhuncao (Jacobaea cannabifolia and J. litvinovii)","authors":"Zhijie He,&nbsp;Zhongyu Tan,&nbsp;Lunrong Zhang,&nbsp;Yue Yin,&nbsp;Yedeli Yerjiang,&nbsp;Bo Bi,&nbsp;Jingshan Bao","doi":"10.1002/ardp.70326","DOIUrl":"10.1002/ardp.70326","url":null,"abstract":"<div>\u0000 \u0000 <p>Fanhuncao (<i>Jacobaea cannabifolia</i> and <i>J. litvinovii</i>) is a traditional Chinese herb with reported antitumor potential. Retrorsine, a pyrrolizidine alkaloid from Fanhuncao, requires CYP3A4‑mediated metabolic activation, but its dual outcomes (anti‑liver cancer efficacy vs. organ‑specific toxicity) remain unclear. To elucidate how CYP3A4-dependent activation of retrorsine drives both anti-liver cancer activity and organ-specific toxicity, and to identify differential cell death pathways in target organs. UPLC-HRMS profiled pyrrolizidine alkaloids in Fanhuncao. Cytotoxicity screening, molecular docking, and molecular dynamics identified retrorsine as the lead compound. Network pharmacology/toxicology predicted targets of dehydro-retrorsine. In vitro assays and Western blotting were performed on hepatoma cells. <i>In vivo</i> efficacy and toxicity were evaluated in H22 tumor-bearing mice. Retrorsine achieved significant tumor growth inhibition at high dose. Mechanistically, it simultaneously inhibited EGFR/PI3K/AKT/mTOR and NF-κB pathways while activating intrinsic mitochondrial apoptosis (altered Bax/Bcl-2, cytochrome c release, Caspase-9/3 activation). Retrorsine upregulated CYP3A4 in tumor cells, suggesting a potential self‑amplifying metabolic loop that requires further validation. However, this efficacy was accompanied by dose-dependent hepatorenal toxicity with organ-specific mechanisms: liver injury via oxidative stress and mitochondrial apoptosis; kidney injury via Caspase-3/GSDME-dependent pyroptosis. Retrorsine is a potent multi-target anti-liver cancer natural product, but its therapeutic window is narrowed by inseparable organ-specific toxicities (hepatic apoptosis vs. renal pyroptosis) arising from CYP3A4-dependent metabolic activation. Future decoupling strategies should focus on targeted delivery, structural modification, or combination therapies.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of Novel Ligands for the Treatment of Cryptococcus neoformans Infection","authors":"Teresa Rocha,&nbsp;Catarina Alves,&nbsp;Carla Lima,&nbsp;Lisa Sequeira,&nbsp;Fernanda Borges,&nbsp;Fernando Cagide,&nbsp;Sofia Benfeito","doi":"10.1002/ardp.70324","DOIUrl":"https://doi.org/10.1002/ardp.70324","url":null,"abstract":"<div>\u0000 \u0000 <p>Fungal pathogens are an escalating global public health concern, particularly in the context of invasive and opportunistic infections. Cryptococcosis, primarily caused by <i>Cryptococcus neoformans var. grubii</i>, can affect multiple organs and often leads to life-threatening meningitis in immunocompromised individuals. Given limited antifungal therapies and emergence of resistance and toxicity-related constraints, the development of novel anti-cryptococcal agents remains an urgent priority. A library of innovative 3-hydroxypyridin-4(1<i>H</i>)-one-based hybrids (<b>5a–f</b>) was synthesized and evaluated for antimicrobial activity against clinically relevant Gram-positive and Gram-negative bacteria, as well as fungal species <i>Candida albicans</i> and <i>C. neoformans</i> var. <i>grubbi</i>. Safety was assessed through cytotoxicity studies in HEK293 and HepG2 cells and hemolytic evaluation, while iron-chelating capacity and lipophilicity were also investigated. All compounds formed stable iron(III) complexes and displayed no significant toxicity up to 25 μM. Series 1 compounds (<b>5a–c</b>) were less lipophilic than Series 2 (<b>5d–f</b>), mainly due to regioisomeric position of hydroxyl group on 2-methyl-4-pyridone scaffold, whereas fluorination increased lipophilicity in both series. Notably, compounds <b>5c–f</b> emerged as potent, selective, and nontoxic antifungal agents against <i>C. neoformans</i> var. <i>grubii</i> (MIC &lt; 16 µg/mL; CC₅₀ &gt; 32 µg/mL; HC₁₀ &gt; 32 µg/mL), highlighting the potential of 3-hydroxypyridin-4(1H)-one-based hybrids as a promising approach for cryptococcal meningitis therapy.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information: Arch Pharm (8/2026)","authors":"","doi":"10.1002/ardp.70329","DOIUrl":"https://doi.org/10.1002/ardp.70329","url":null,"abstract":"","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRET-Based Approaches for Ion Channels: Emerging Applications and Future Directions","authors":"Nadine Kock,&nbsp;Laura Heitzer,&nbsp;Joana Massa,&nbsp;Marvin Taterra,&nbsp;Marcel Bermúdez,&nbsp;Oliver Koch,&nbsp;Matthias Schiedel","doi":"10.1002/ardp.70325","DOIUrl":"https://doi.org/10.1002/ardp.70325","url":null,"abstract":"<p>Bioluminescence resonance energy transfer (BRET) is a technique based on energy transfer between a luminescent enzyme and a fluorescent acceptor. Since its first description in 1999, BRET has been widely applied in chemical biology research and drug discovery. Today, it is regarded as one of the most versatile methods for investigating the dynamics of ligand–protein and protein–protein interactions, both in cell-free systems and living cells. Owing to several advantages, including compatibility with high-throughput screening, suitability for cellular target engagement studies, and the ability to monitor real-time kinetics, BRET-based binding assays have become indispensable tools, particularly in early-stage drug discovery. Consequently, over the past decade these approaches have been extensively used for major drug target classes such as G protein-coupled receptors (GPCRs), kinases, and proteases. Despite the high relevance of ion channels as drug targets—approximately one-fifth of all approved drugs act on them—BRET-based assays have so far played only a limited role in this field. Here, we summarize recent applications of BRET-based methods for ion channels with a particular focus on approaches for studying ligand-ion channel interactions, highlighting current challenges and, more importantly, the significant potential of this technology to advance ion channel–focused drug discovery.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70325","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}