Mini reviews in medicinal chemistry最新文献

{"title":"Smart Pulmonary Drug Delivery: pH-sensitive Microparticulate System for Next-generation Asthma Therapeutics.","authors":"Anjali Kumari, Vishal Chauhan, Muinur Rahman, Alka Diwakar, Raushan Kumar, Sunny Rathee, Umesh K Patil, Meenakshi Gupta","doi":"10.2174/0113895575456618260819075005","DOIUrl":"https://doi.org/10.2174/0113895575456618260819075005","url":null,"abstract":"<p><p>Asthma is a prevalent chronic respiratory disease that is still a major concern for the global population, and it has been estimated to affect no less than 400 million people in the year 2025, mostly affecting children. Symptoms include persistent inflammation in the airways, attacks of bronchospasms, and resulting wheezing, shortness of breath, and coughing. Although there have been highly effective therapies available for patients in the form of inhalers, there have been concerns associated with the current therapies, including a lack of targeting, the need for repeated dosing, and the potential for unwanted side effects. However, to address these challenges, emerging approaches have used new delivery systems, specifically pH-sensitive microparticles. During the attack, there is a pH imbalance due to inflammation and the secretion of excess amounts of mucus. pH-responsive microparticles (1-5 μm), formulated with biocompatible materials such as chitosan, PLGA, and Eudragit, have been shown to deliver drugs to the deeper respiratory tracts and provide a sustained drug release. Furthermore, the importance of pH-responsive microparticles has been introduced in this review, wherein it has been described how these particles are capable of reducing inflammation, reducing systemic distribution, and also recovering lung functions. pH-sensitive microparticles can improve patient compliance with treatment by allowing fewer doses to be taken. This is particularly promising, especially given the worldwide burden of asthma in developing countries, where effective, precise, and simple asthma control is needed.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906608","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":"Recent Advancements in Reinforced Polymer Metal Nanohybrids for Effective Radiation Shielding: A Short Review.","authors":"Nivedita Swarnkar, Divya Chauhan, Sanjeev Kimothi, Sachin Chawla, Abhishek Paswan, Pankaj Chamoli","doi":"10.2174/0113895575426947260131194950","DOIUrl":"https://doi.org/10.2174/0113895575426947260131194950","url":null,"abstract":"<p><p>Ionised radiation plays a crucial role in various fields, including diagnostic imaging, radiotherapy, industrial processes, and scientific research. With the increasing use of ionising radiation, there is a growing need for effective shielding to minimise harmful exposure. Traditionally, leadbased shields have been used; however, they pose significant health and environmental hazards, particularly due to lead dust exposure, which is a major concern for healthcare workers. Consequently, alternatives such as polymer-based metal nanohybrids are emerging as promising options for radiation protection. This paper reviews the latest research on EMI shielding using polymer-based metal nanohybrids, with a particular focus on their applications in radiation shielding. It examines the influence of polymer matrix materials and the effects of polymer and filler particle sizes on the attenuation of radiation, including X-rays, gamma rays, and microwaves. Key materials discussed polymers (such as PMMA, PVDF), nanostructures (e.g., Bi2O3, ZnO, Fe2O3), and hybrid nanostructures (e.g., PMMA/GO, PVDF/BaTiO2, WC, BaFe12O19, NiFe2O4). The paper explores their structure, properties, and advantages for radiation shielding. The shielding efficiency of these materials is assessed by using parameters such as the mass attenuation coefficient, linear attenuation coefficient, half-value layer, tenth-value layer, and mean free path. Compared to conventional shielding materials, polymer-based metal nanohybrids offer superior performance due to the unique properties of nanoparticles, including enhanced attenuation coefficients, lightweight, ease of fabrication, thermal stability, and electrical conductivity. These characteristics make them more efficient and environmentally friendly alternatives compared to traditional lead-based shielding.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906492","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":"Molecular Dynamics Simulations in Modern Medicinal Chemistry.","authors":"Süleyman Selim Çınaroğlu","doi":"10.2174/0113895575482194260819170202","DOIUrl":"https://doi.org/10.2174/0113895575482194260819170202","url":null,"abstract":"<p><p>Molecular dynamics (MD) simulations have become an increasingly important component of modern medicinal chemistry and structure-based drug discovery, providing atomistic insight into protein-ligand interactions that extends beyond static experimental structures and docking models. By explicitly accounting for conformational flexibility, solvent effects, and time-dependent behaviour, MD simulations enable the refinement of binding poses, the identification of transient and allosteric sites, and the quantitative estimation of binding thermodynamics and kinetics, the latter increasingly accessible through Markov state models (MSMs) and milestoning approaches that reconstruct long-timescale behaviour from ensembles of short trajectories. In this mini-review, we provide a practical overview of classical atomistic MD methodologies commonly used in medicinal chemistry, including force-field-based simulations, enhanced sampling techniques, and free-energy calculation methods such as alchemical and end-point approaches. Emphasis is placed on the strengths and limitations of each technique, with particular attention to their appropriate use across different stages of the drug discovery pipeline. We further discuss best practices for system preparation, simulation protocol design, convergence assessment, and reproducibility, highlighting common pitfalls that can lead to overinterpretation of simulation results. Selected examples illustrate how MD simulations have informed medicinal chemistry decisions in lead identification and optimisation. Finally, we briefly outline emerging directions, including the integration of machine learning, ensemble-based approaches, and next-generation force fields, which are expected to further expand the role of MD simulations in medicinal chemistry.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906507","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":"Regulation of PI3K Signaling by lncRNAs in Breast Cancer: A Mini-Review.","authors":"Azita Asadi, Mehran Molavand, Bahman Yousefi","doi":"10.2174/0113895575458901260819095156","DOIUrl":"https://doi.org/10.2174/0113895575458901260819095156","url":null,"abstract":"<p><p>Despite remarkable advancements, the treatment of breast cancer remains a serious challenge. In recent decades, extensive studies have been conducted to identify new therapeutic targets for the treatment of breast cancer. Among these therapeutic targets that have gained attention in recent years are lncRNAs. These molecules appear to affect proliferation, metastasis, and drug resistance in cancer cells by regulating multiple signaling pathways. Among the signaling pathways implicated in breast cancer, the PI3K/AKT/mTOR pathway is one of the most important. Given the frequent dysregulation of the PI3K/AKT/mTOR pathway in breast cancer, numerous recent studies have investigated its interplay with lncRNAs. Emerging evidence indicates that lncRNAs regulate the PI3K/AKT/mTOR pathway by modulating microRNA availability, influencing transcriptional programs, and serving as molecular platforms for chromatin-modifying complexes. This mini-review synthesizes recent evidence on lncRNAs targeting the PI3K/AKT/mTOR cascade in breast cancer, summarizing molecular mechanisms, functional consequences for proliferation, invasion, and therapy resistance, and available in vitro and in vivo evidence. Representative oncogenic lncRNAs (e.g., HOTAIR, DANCR, and LINC01133) and tumor-suppressive lncRNAs (e.g., MEG3 and ZFAS1) are discussed, together with their potential as therapeutic targets. Finally, the current challenges and future perspectives for integrating lncRNAtargeted approaches with PI3K pathway inhibition in breast cancer therapy are highlighted.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906537","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":"s-triazine-based Derivatives as Anticancer Agents.","authors":"Doralice Giorgini, Jacopo Castagnoli, Lorenzo Filidei, Riccardo Di Leo, Silvia Salerno, Federico Da Settimo, Tiziano Marzo, Elisabetta Barresi, Emma Baglini, Sabrina Taliani","doi":"10.2174/0113895575477125260820031228","DOIUrl":"https://doi.org/10.2174/0113895575477125260820031228","url":null,"abstract":"<p><p>Heterocyclic derivatives represent the primary scaffold for numerous medicinal agents of utmost importance for humanity. Among them, triazine derivatives, and particularly the s-triazine scaffold, have long represented a cornerstone in medicinal chemistry research due to their broad pharmacological versatility. This heterocyclic system is a key structure in the design of therapeutic agents exhibiting antitrypanosomal, antiviral, antimicrobial, anti-inflammatory, antidiabetic, and anticancer activities. The s-triazine core represents a privileged scaffold, allowing rational optimization through targeted substitution patterns at different positions. Indeed, the triazine ring is characterized by the replacement of 3 carbon atoms of a benzene ring with three nitrogens, affording three easily modified sites at positions 2, 4, and 6, which can be variously substituted to modulate physiological and biological activities. In this review, we will focus on the structural and pharmacological features of s-triazine-based compounds developed as anticancer agents. Indeed, cancer is an increasing worldwide emergency, and its incidence and mortality will double in the next twenty years. Thus, the development of innovative and powerful anticancer agents remains one of the biggest challenges in the research world. In this respect, we provide an overview of the recent primary literature concerning the development of s-triazine-based antitumor agents, focusing on the most potent compounds acting on specific molecular targets and discussing the structure-activity relationships (SARs), when available. The aim is to provide important principles for the future development of new anticancer agents with greater potency against drug-sensitive and drug-resistant cancers.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906606","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":"Vanillin and its Derivatives: Therapeutic Strategies in Modern Medicine.","authors":"Renu Verma, Uma Agarwal, Bhumika Chauhan, Harpreet Singh, Arun K Mishra, Nitin Kumar, Arvind Kumar","doi":"10.2174/0113895575461522260820050915","DOIUrl":"https://doi.org/10.2174/0113895575461522260820050915","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Vanillin, a phenolic aldehyde, is the primary component of the vanilla bean's ethanolic extract. Synthetic vanillin is now more commonly used as a flavoring in foods, beverages, and pharmaceuticals. Natural vanilla extract consists of several hundred derivatives, while artificial vanilla flavoring is often a synthetic ethanol solution of pure vanillin. The first commercial synthesis of vanillin began with eugenol, and today, it is made from guaiacol or lignin.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This narrative review aggregates and critically assesses available literature on vanillin and its synthetic derivatives. A thorough literature review was conducted using prominent scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar, covering papers from 2000 to 2024, with a specific focus on recent research. Experimental and review studies concerning the synthesis, structural changes, pharmacological activities, toxicological features, and structure- activity connections of vanillin and its derivatives were systematically examined and analyzed. The review emphasizes the biological evaluations, modes of action, and therapeutic potential of vanillinderived drugs in various illness types.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Comprehensive evaluation of vanillin and its derivatives revealed their broad pharmacological spectrum, including significant neuroprotective effects against neurodegenerative disorders such as Alzheimer's disease and potent anti-diabetic properties. In addition, Several vanillin derivatives demonstrated promising antimicrobial and anticancer activities, emphasizing their therapeutic potential. The review highlights that diverse synthetic strategies such as Schiff base formation, Azo-Schiff base reactions, Williamson ether synthesis, Steglich esterification, Claisen-Schmidt condensation, and Mannich or reductive amination reactions are effectively employed to design and modify vanillin structures. These synthetic methods target functional groups like hydroxyl, methoxy, and aldehyde moieties, enabling the generation of novel bioactive derivatives with improved pharmacological profiles. Aldehyde (CHO) groups in vanillin are more susceptible to substitution than other functional groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Vanillin is a structurally versatile phenolic aldehyde with broad pharmacological potential. Structural modifications of its hydroxyl, methoxy, and aldehyde groups significantly enhance biological activities, including neuroprotective effects against Alzheimer's disease, anti-diabetic, antimicrobial, and anticancer properties. The aldehyde moiety plays a key role in synthetic diversification through reactions such as Schiff base formation, Mannich reaction, and Claisen-Schmidt condensation, enabling the development of potent bioactive derivatives. Although promising preclinical results highlight the therapeutic potential of vanillin-based compounds, further pharmacokin","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906533","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":"Mitochondrial Dynamics and Bioenergetic Reprogramming: Drivers of Cancer Therapy Resistance.","authors":"Varsha Johariya, Vaibhav Singh, Rakesh Kore, Santosh Kumar, Ravichandran Veerasamy, Amit K Tiwari, Harish Rajak","doi":"10.2174/0113895575489044260817065455","DOIUrl":"https://doi.org/10.2174/0113895575489044260817065455","url":null,"abstract":"<p><p>Mitochondria, often referred to as the powerhouses of the cell, play a pivotal role in maintaining cellular homeostasis through the regulation of energy production, redox balance, and apoptosis. Recent evidence highlights the significance of mitochondrial dynamics, fusion, fission, biogenesis, and mitophagy, enabling cells to adapt to changing physiological and environmental conditions. Dysregulation of these dynamic processes alters mitochondrial function, promoting metabolic reprogramming, evasion of apoptosis, and resistance to chemotherapy. Specifically, enhanced mitochondrial fission is often linked to increased metabolic flexibility and resistance to cell death, while aberrant fusion supports mitochondrial quality control under cellular stress. Additionally, tumour cells also exhibit bioenergetic flexibility, dynamically switching between OXPHOS and glycolysis to meet energy demands and overcome therapeutic stress. This metabolic change influences ROS levels, directly affecting the efficacy of anticancer agents in cancer cells. Such adaptations are now recognised as hallmarks of drug-resistant cancers. This review explores the mechanistic interplay between mitochondrial dynamics and cancer bioenergetics, emphasising how these processes contribute to drug resistance. We also focus on emerging therapeutic strategies, particularly smallmolecule inhibitors targeting mitochondrial fusion and fission that offer promising potential to restore chemosensitivity and disrupt cancer cell survival. A deeper understanding of mitochondrial behaviour in cancer may reveal novel therapeutic targets for the development of more effective and durable cancer treatments.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906434","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":"Pyrimidine-containing Heterocyclic Anticancer Agents: Systematic Development, SAR, and Mechanistic Pathways.","authors":"Bhim Singh, Ankita Devi, Vikas Jaitak","doi":"10.2174/0113895575489289260815183816","DOIUrl":"https://doi.org/10.2174/0113895575489289260815183816","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer remains one of the most prominent causes of death, affecting millions of lives globally, thereby posing a significant disease burden. Heterocyclic scaffolds, particularly pyrimidines, have proven effective owing to their versatile activity across various cancer types. This review aims to provide an extensive compilation of pyrimidine-based hybrid molecules as promising anti-proliferative agents, highlighting their synthesis, multi-target capabilities, key signaling pathways, structure-activity relationships (SARs), molecular targets, and therapeutic potential against cancer cells.</p><p><strong>Methods: </strong>A comprehensive literature survey was conducted using PubMed, Elsevier, Google Scholar, ScienceDirect, ACS, RSC, and PubChem to identify relevant reviews and research articles published between 2020 and 2025. The collective study was analyzed to evaluate pyrimidine-based hybrid structural modification, molecular targets, anticancer mechanism, and pharmacological properties.</p><p><strong>Result: </strong>Pyrimidine-based hybrid molecules have demonstrated antiproliferative activity, with several derivatives demonstrating excellent inhibitory potency, enhanced target selectivity, and improved pharmacokinetic characteristics. Pyrimidine hybrids effectively modulate multiple oncogenic targets and signaling pathways, including PI3K/AKT, CDKs, EGFR, HSP90a, and HDAC, leading to cell cycle arrest and apoptosis and inhibiting tumor growth. Further SAR revealed that strategic substitution on the pyrimidine scaffold significantly increased bioavailability, reduced toxicity, and improved target selectivity.</p><p><strong>Discussion: </strong>The literature indicates that pyrimidine-based hybrid molecules have significant potential as multitargeted anticancer agents, addressing the limitations of conventional single-target therapies. Their structural diversity was shown to modulate multiple cancer-related signaling pathways. The study highlights their promising, valuable lead scaffold for the development of next-generation anticancer agents.</p><p><strong>Conclusion: </strong>Pyrimidine-containing hybrids emerge as a privileged scaffold in medicinal chemistry for the development of effective, multitargeted anticancer agents with improved pharmacological profiles and reduced off-target effects. Therefore, further structural optimization and mechanistic analysis, along with preclinical evaluation, suggest that pyrimidine-based molecules hold significant promise for cancer therapy.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906500","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":"Pharmacogenomic and Medicinal Chemistry Perspectives on Off-label Drug Use.","authors":"Mariana Meira Scudeler, Isadora Renck Scherer, Gabriel Vaisam Castro, Gabriéli Luiza Steffens Knapp, Lucas Brandalise Menezes, Yara Costa Netto Muniz, Juliana Dal-Ri Lindenau","doi":"10.2174/0113895575476948260813040856","DOIUrl":"https://doi.org/10.2174/0113895575476948260813040856","url":null,"abstract":"<p><strong>Introduction: </strong>Off-label drug use (OLDU) is frequent in populations insufficiently represented in clinical trials, including pediatrics, rare diseases, and psychiatry. Although it broadens therapeutic options, uncertainty regarding safety and response remains a central concern. Physical chemistry properties influence drug distribution, target promiscuity, and exposure profiles in offlabel contexts. Because the biological processes that translate these intrinsic molecular properties into pharmacokinetic and pharmacodynamic phenotypes are modulated by genetic variability, pharmacogenomics may provide a complementary strategy for anticipating interindividual differences in safety and efficacy.</p><p><strong>Materials and methods: </strong>This narrative review integrates pharmacogenomics (PGx) evidence from curated clinical resources (ClinPGx, CPIC, DPWG, and regulatory sources) with principles of medicinal chemistry, prioritizing mechanistic evidence linking genetic variability to drug response variability in commonly prescribed off-label therapies across selected therapeutic areas.</p><p><strong>Results: </strong>Across the therapeutic areas examined, several drugs with frequent off-label use were identified as having available pharmacogenetic information. A subset of these agents was further discussed, considering mechanistic considerations derived from medicinal chemistry principles.</p><p><strong>Discussion: </strong>Intrinsic molecular characteristics help explain biodistribution patterns and off-target effects observed during off-label prescribing. Gene-drug interactions involving metabolizing enzymes and transporters consistently influence drug response. Evidence specifically designed for OLDU remains limited.</p><p><strong>Conclusion: </strong>The convergence of medicinal chemistry and pharmacogenomics may offer a promising framework to enhance safety and precision in off-label prescribing. Although direct evidence in these settings remains limited, the established influence of genetic variation on drug pharmacokinetics and pharmacodynamics provides a biologically plausible rationale for exploring PGx-guided approaches in OLDU.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891939","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":"Awareness of Potential Off-target Effects of Nucleoside Reverse Transcriptase Inhibitors on Telomerase in Patients with Familial Pulmonary Fibrosis.","authors":"Matheus Reck Dutra, Lucas Reck Dutra, Juliana Dal-Ri Lindenau, Yara Costa Netto Muniz","doi":"10.2174/0113895575476965260812094757","DOIUrl":"https://doi.org/10.2174/0113895575476965260812094757","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Familial Pulmonary Fibrosis (FPF) is a lung disease, a subset of which is associated with mutations in telomere-related genes, causing breathing difficulties and compromising quality of life. Telomere length is maintained and extended by telomerase, a reverse transcriptase enzyme that uses an RNA template, generating repetitive sequences rich in guanosine. However, heterozygous loss-of-function mutations in the TERT gene result in telomerase haploinsufficiency, reducing enzyme activity and contributing to earlier disease onset. In this context, it is important to evaluate the potential effects of NRTIs on telomerase, particularly whether these drugs may inhibit its activity. This review discusses the potential implications of this interaction for patients with FPF.</p><p><strong>Methods: </strong>This study is based on a narrative literature search conducted in the PubMed database, using combinations of the relevant keywords, regardless of their year of publication.</p><p><strong>Results: </strong>A literature review identified studies investigating the effects of NRTIs on telomerase activity. Overall, the available evidence indicates that several NRTIs, depending on the study design and the specific molecule evaluated, may inhibit telomerase activity as an off-target effect, although a limited number of studies have reported conflicting findings.</p><p><strong>Discussion: </strong>FPF patients with HIV or those receiving Pre-Exposure Prophylaxis (PrEP) are treated with Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs). This class of medications includes molecules such as tenofovir, which may exert an off-target inhibitory effect on telomerase. Through this inhibition, telomeres cannot be elongated, and given the reduced telomerase availability, progressive telomere shortening occurs. In cases of telomerase haploinsufficiency, this inhibition could lead to symptom progression and poorer prognosis.</p><p><strong>Conclusion: </strong>These findings suggest that caution may be warranted for patients with genetically confirmed telomere-related FPF who require NRTI therapy, considering the potential off-target effects of these drugs on telomerase. Further clinical and mechanistic studies are needed to clarify whether NRTI exposure influences disease progression and prognosis.</p>","PeriodicalId":18548,"journal":{"name":"Mini reviews in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887925","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}