Drug Metabolism Reviews最新文献

{"title":"Phase II metabolism in xenobiotic biotransformation: general mechanisms and the underestimated role of microbial systems.","authors":"Aleksandra Pietrzak, Barbara Dąbrówka, Justyna Popiół, Elżbieta Pękala, Karolina Słoczyńska","doi":"10.1080/03602532.2025.2582864","DOIUrl":"10.1080/03602532.2025.2582864","url":null,"abstract":"<p><p>Microbial phase II biotransformation, involving conjugation reactions such as glycosylation, sulfation, and glucuronidation, is increasingly recognized as a valuable <i>in vitro</i> model for mammalian xenobiotic metabolism, particularly drug metabolism. Fungi, especially <i>Cunninghamella</i> species, demonstrate a notable capacity to produce conjugated metabolites, while bacteria also contribute to this process. Although microbial pathways often parallel mammalian metabolism, key differences exist - for example, glycosylation predominates in microbes, whereas glucuronidation is more common in mammals. Microbial biotransformation enables the production of novel and rare metabolites with potentially enhanced pharmacological properties and provides an efficient, eco-friendly alternative to complex chemical synthesis. Furthermore, microorganisms play a significant role in the detoxification and bioremediation of xenobiotics by increasing solubility and reducing toxicity of harmful compounds. Despite some limitations and discrepancies compared to mammalian systems, microbial models offer valuable tools for drug development, metabolite production, and environmental applications. Continued research into the enzymatic mechanisms, metabolic diversity, and ecological roles of microbial phase II pathways is essential to fully exploit their potential in pharmaceutical and environmental sciences.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"1-25"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CYP24A1: the pivotal regulator of vitamin D homeostasis, pathophysiology in metabolic and genetic disease, and emerging target for precision medicine.","authors":"Navodi Sandamini Jayathilaka, Arunodya Vishwanthi Weththasinghe, Dhanasekara Mudiyanselage Krishanthi Jayamini Wijekoon, Nila Ganamurali, Sarvesh Sabarathinam","doi":"10.1080/03602532.2025.2608610","DOIUrl":"10.1080/03602532.2025.2608610","url":null,"abstract":"<p><p>CYP24A1 (25-hydroxyvitamin D₃ 24-hydroxylase) functions as the essential catabolic 'off-switch' of the vitamin D endocrine axis. As a mitochondrial cytochrome P450 enzyme, it tightly regulates calcitriol (1,25(OH)₂D₃) levels through a remarkably sensitive negative feedback mechanism, capable of a 20,000-fold transcriptional response-by converting biologically active vitamin D metabolites into the inactive end-product calcitroic acid. Its expression is governed by opposing endocrine cues from Parathyroid Hormone (PTH) and Fibroblast Growth Factor 23 (FGF23), with FGF23-mediated induction of CYP24A1 playing a key role in lowering calcitriol during states of phosphate excess. Pathogenic loss-of-function variants in CYP24A1 underlie Idiopathic Infantile Hypercalcemia (IIH) type 1, whereas acquired dysregulation contributes significantly to chronic kidney disease (CKD). In CKD, sustained FGF23 elevation drives aberrant CYP24A1 activation, promoting functional vitamin D deficiency and secondary hyperparathyroidism. Emerging studies also implicate inflammation-induced CYP24A1 upregulation in metabolic diseases and cancer, establishing it as a molecular basis for vitamin D resistance. The advent of selective CYP24A1 inhibitors represents a promising therapeutic strategy to optimize vitamin D signaling and control hypercalcemia. Incorporating pharmacogenetic markers (e.g. rs2248359) and functional indices such as 24,25(OH)₂D measurements supports individualized vitamin D dosing and advances precision medicine for vitamin D-related disorders.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"69-84"},"PeriodicalIF":3.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review on the application of metalloporphyrin catalysts as cytochrome P450 enzyme mimics in biomimetic modeling.","authors":"Ahmed Qasim Abdulhussein, Diána Balogh-Weiser, Balázs Volk, György Tibor Balogh","doi":"10.1080/03602532.2026.2625088","DOIUrl":"10.1080/03602532.2026.2625088","url":null,"abstract":"<p><p>Drug research, particularly in the early discovery phase, increasingly seeks cost-effective and reliable <i>in vitro</i> models to predict drug metabolism. Metalloporphyrins (MPs), due to their structural and functional resemblance to the heme group of cytochrome P450 enzymes (CYP450s), have emerged as versatile biomimetic catalysts for oxidative reactions. This review focuses specifically on metalloporphyrin-based biomimetic catalysis for oxidative drug metabolism studied in scientific papers publishedin the last 10 years (2015-2025). Unlike previous reviews, we highlight the comparative advantages and limitations of MP systems versus enzymatic models (microsomes, recombinant CYP450s), including aspects of selectivity, functional group tolerance, and scalability. We further discuss recent innovations in immobilization strategies, nanostructured supports, and continuous-flow applications that expand MPs' utility in drug metabolism studies. While challenges remain, particularly regioselectivity and oxidation of unactivated C-H bonds, we conclude that MPs serve as complementary tools for metabolite synthesis and mechanistic investigations, and their integration with modern microreactors and peptide-based designs holds promise for future biomimetic drug metabolism research.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"121-141"},"PeriodicalIF":4.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolism of new drug modalities research advances - 2024 year in review.","authors":"Bin Ma, Upendra A Argikar, Luying Chen, Lionel Cheruzel, Sungjoon Cho, Ting-Jia Gu, Simon Hauri, Valerie M Kramlinger, Xiuli Li, Joyce Liu, Simone Schadt, Herana Kamal Seneviratne, Rachel Liuqing Shi, Lloyd Wei Tat Tang, Donglu Zhang, Guo Zhong, S Cyrus Khojasteh","doi":"10.1080/03602532.2025.2542220","DOIUrl":"10.1080/03602532.2025.2542220","url":null,"abstract":"<p><p>New drug modalities (NDMs) have gained significant popularity and attention in recent years due to their ability to target previously undruggable pathways and offer new strategies for tackling complex diseases. This trend is reflected in our review, which encompasses 17 publications, an increase from 11 last year and includes a growing number of contributors across industry and academia. We have focused on five categories of NDMs: (1) Peptides with an emphasis on macrocyclic structures; (2) Bivalent protein degraders, also known as proteolysis-targeting chimeras (PROTACs); (3) Conjugated drugs, including peptide-drug and antibody-drug conjugates; (4) Antisense oligonucleotides and <i>N</i>-acetylgalactosamine (GalNAc) conjugated oligonucleotides; and (5) Covalent inhibitors.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"467-504"},"PeriodicalIF":3.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclodextrins grafted magnetite (Fe₃O₄) nanocarriers for anticancer therapy.","authors":"Sivakumar Krishnamoorthy, Divya Annaparvathi Suyamburaj","doi":"10.1080/03602532.2025.2549294","DOIUrl":"10.1080/03602532.2025.2549294","url":null,"abstract":"<p><p>This comprehensive review explores the therapeutic promise of cyclodextrin-grafted magnetite (Fe₃O₄) nanocarriers in anticancer applications, focusing on their design, drug delivery mechanisms, biological stability, and therapeutic performance. Systems integrating cyclodextrins (cds) with Fe₃O₄ nanoparticles (Fe₃O₄-cd-drug) have been developed for delivery of key anticancer agents such as docetaxel, irinotecan, paclitaxel, and doxorubicin across 11 cancer cell types. Results demonstrate up to 60% reduced cancer cell viability when using magnetite nanoparticle (Fe₃O₄-np)-cds-docetaxel/irinotecan/doxorubicin systems compared to the pristine drug. cd grafting enhances nanoparticle hydrophilicity, drug encapsulation, colloidal stability, and biocompatibility, enabling sustained and targeted drug release. Direct grafting of cds onto Fe₃O₄ yields superior cytotoxicity of 93% death of epidermoid carcinoma (A431) cells with Fe₃O₄-np-cds-irinotecan system compared to linker-mediated systems. In the case of Fe₃O₄-np-cds-doxorubicin system tested on human breast cancer cell (MCF-7) cells shows 38% cell death and adding hyperthermia kills 30% of cells. Compared to alternative grafting like polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), metal-organic frameworks (MOFs), or carbon-based materials, cds offer unique advantages including Food and Drug Administration (FDA)-approved biocompatibility, pH-sensitive release, and support for combination therapies. Cluster analysis categorized Fe₃O₄-cd-drug systems based on cytotoxic efficiency and drug concentration, identifying structure-function relationships and highlighting the superiority of systems with multimodal surface engineering. Mechanistic insights reveal endocytosis-mediated uptake, lysosomal-triggered drug release, reactive oxygen species (ROS) generation via Fenton-like reactions, and enhanced cytotoxicity under hyperthermia. Despite these advances, gaps remain in understanding inclusion complex chemistry, biodistribution, and structure-activity relationships. This review highlights the potential of Fe₃O₄-np-cds-drug systems and emphasizes the urgent need for systematic molecular and material-level studies to optimize Fe₃O₄-cd-drug systems for translational cancer therapy.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"505-522"},"PeriodicalIF":3.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analytical techniques for methyldopa and metabolites: a comprehensive review.","authors":"Hemn A H Barzani, Seerwan Hamadameen Sulaiman, Rebaz Anwar Omer, Ali Hussein Mer, Hoshyar Saadi Ali","doi":"10.1080/03602532.2025.2560487","DOIUrl":"10.1080/03602532.2025.2560487","url":null,"abstract":"<p><p>Methyldopa, a centrally acting α2-adrenergic agonist, remains a key antihypertensive drug, particularly prescribed for pregnant and renal-impaired patients. Its clinical significance has led to extensive research aimed at developing reliable analytical methods for its accurate, sensitive, and selective determination in pharmaceutical formulations and biological matrices. Relevant literature was retrieved from Scopus, Web of Science, ScienceDirect, PubMed, and Google Scholar, restricted to English-language publications. This review critically examines the diverse analytical approaches used for Methyldopa quantification, outlining their principles, advantages, limitations, and applicability in both advanced and resource-limited settings. Chromatographic methods, especially high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS/MS), remain the most robust techniques, offering excellent sensitivity (LOD: 10-50 ng/mL for HPLC; as low as 0.7-15 ng/mL for LC-MS/MS) with rapid analysis times. While LC-MS/MS provides superior detection, it is limited by high costs and technical expertise requirements. Electrochemical methods, particularly voltammetry, stand out for their affordability, rapid analysis, and feasibility in decentralized laboratories, achieving LOD values as low as 0.01-0.05 µM. Spectrophotometric approaches, primarily UV-Vis, remain the simplest and most cost-effective options, making them useful for routine quality control, though with reduced selectivity and higher detection limits. Key analytical challenges include Methyldopa's low concentration in biological fluids, chemical instability, and matrix interferences. This review provides a comparative evaluation of chromatographic, spectrophotometric, and electrochemical techniques, emphasizing the need for portable, low-cost platforms to expand accessibility in therapeutic monitoring. Overall, it offers critical insights for advancing Methyldopa analysis and improving clinical management in diverse healthcare settings.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"559-594"},"PeriodicalIF":3.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/03602532.2025.2541147","DOIUrl":"10.1080/03602532.2025.2541147","url":null,"abstract":"","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"614"},"PeriodicalIF":3.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Traditional Chinese medicine and gut microbiota: biotransformation, interaction, and implications for chronic disease treatment.","authors":"Xia Hao, Jinbo Zhang, Ruishuang Ma, Bin Yao, Wei Yang","doi":"10.1080/03602532.2025.2520768","DOIUrl":"10.1080/03602532.2025.2520768","url":null,"abstract":"<p><p>The gut microbiota (GM), often regarded as a vital 'functional organ,' plays a crucial role in human physiological processes. GM is involved in substance metabolism, especially the biotransformation of pharmaceuticals. It modulates drug pharmacological activity and bioavailability through various metabolic pathways. Since traditional Chinese medicine (TCM) is primarily administered orally, its active compounds inevitably interact with the GM. This review systematically explores the bidirectional interplay between TCM and GM. GM metabolizes TCM components via enzymatic reactions (e.g. hydrolysis, reduction, and deconjugation) and interactions with metabolites, thereby enhancing bioavailability and sometimes modifying pharmacological properties. Conversely, TCM influences GM composition and function by promoting beneficial taxa, restoring microbial balance, and regulating microbial metabolites such as short-chain fatty acids and bile acids. The TCM-GM interaction shows promise in treating chronic diseases, such as inflammatory bowel disease, mental disorders, and cardiovascular diseases. However, challenges remain in fully understanding these interactions due to the complexity of TCM formulations and individual variations in GM composition. Future research should employ multi-omics approaches to develop personalized TCM therapies based on individual GM profiles.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"338-361"},"PeriodicalIF":3.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimolecular interactions from Chinese medicines activate nuclear receptor conformational changes: a potential strategy for anti-inflammatory therapy.","authors":"Xuechun Yu, Ying Zhang, Bingxin Wu, Bixin Zhao, Caiyan Wang","doi":"10.1080/03602532.2025.2558654","DOIUrl":"10.1080/03602532.2025.2558654","url":null,"abstract":"<p><p>Nuclear receptors (NRs) are among the most common transcriptional regulators in the human body. Currently, liver X receptor (LXR), pregnane X receptor (PXR), farnesoid X receptor (FXR), and peroxisome proliferator-activated receptor (PPAR) are significant targets in the management of inflammatory metabolic disorders. Traditional Chinese medicine has shown good results in treating inflammatory metabolic diseases, but no one has yet summarized the mechanism of action of Chinese medicine monomers on these four NRs. This article summarizes the key binding sites for endogenous agonists and Chinese medicine monomers with NRs, as well as the patterns of NR conformational changes after interaction. This provides a basis for future structural research in the development and optimization of Chinese medicine medicines. We found that the same Chinese medicine monomer can act on different NRs and exert different physiological functions and that the same NR can be activated by different Chinese medicine monomers. This holistic nature is highly compatible with the multicomponent and multi-targeted therapeutic effects of Chinese medicines, making the development of NR-based drugs feasible.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"535-558"},"PeriodicalIF":3.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biotransformation research advances - 2024 year in review.","authors":"Lionel Cheruzel, Upendra A Argikar, Pietro Brunetti, Maria Chatzopoulou, Sungjoon Cho, Rachel D Crouch, Deepika Dhaware, Kevin M Johnson, Valerie Kramlinger, Joyce Liu, Bin Ma, Hlaing Maw, Karoline Rehm, Herana Kamal Seneviratne, Lloyd Wei Tat Tang, Guo Zhong, S Cyrus Khojasteh","doi":"10.1080/03602532.2025.2538676","DOIUrl":"10.1080/03602532.2025.2538676","url":null,"abstract":"<p><p>This is the ninth installment of this annual review. In line with previous years, the primary objective is to highlight articles deemed by us of significant interest in the broad field of biotransformation. Sixteen manuscripts have been collated and presented herein accompanied by a synopsis, commentary and relevant figures. This year's collection delves into five main areas: (1) the metabolism and disposition of various investigative and approved drugs, (2) non-CYP enzymatic biotransformation, (3) novel models and approaches, (4) the role of gut microbiota, and (5) modulating drug-metabolizing enzyme activities.</p>","PeriodicalId":11307,"journal":{"name":"Drug Metabolism Reviews","volume":" ","pages":"432-466"},"PeriodicalIF":3.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}