Pharmaceutical Science Advances最新文献

{"title":"Artificial intelligence in human immunodeficiency virus mutation prediction and drug design: Advancing personalized treatment and prevention","authors":"Karamot O. Oyediran ,&nbsp;Peace-Ofonabasi O. Bassey ,&nbsp;Deborah A. Ogundemuren ,&nbsp;Abdullahi Abdulraheem ,&nbsp;Chukwuemeka P. Azubuike ,&nbsp;Andrew N. Amenaghawon ,&nbsp;Margaret O. Ilomunaya","doi":"10.1016/j.pscia.2025.100080","DOIUrl":"10.1016/j.pscia.2025.100080","url":null,"abstract":"<div><div>Despite significant advancements in highly active antiretroviral therapy (HAART), Human Immunodeficiency Virus (HIV) remains a global health challenge due to its high mutation rate, drug resistance, and the complexity of treatment optimization. Artificial intelligence (AI) has emerged as a transformative tool in HIV research, offering innovative solutions for predicting viral mutations, optimizing drug discovery and formulation design. However, challenges such as limited access to diverse datasets, ethical concerns, and model interpretability hinder the full potential of AI in HIV research. This review highlights gaps in AI-driven HIV research and explores advancements to address these challenges. AI-driven platforms, such as DeepHIV and geno2pheno, have demonstrated success in forecasting resistance mutations and guiding therapeutic decisions. AI is also revolutionizing drug formulation development by enhancing solubility, bioavailability, and stability, while improving patient adherence through advanced delivery systems. Current applications of AI in HIV mutation prediction, drug discovery, and formulation optimization have highlighted the potential of AI towards HIV management and eradication while addressing gaps in data availability and model transparency. By integrating structural, pharmacological, and clinical data, AI provides a comprehensive framework for rational drug design and personalized treatment strategies. By leveraging AI-driven insights, HIV treatment and prevention can become more personalized, efficient, and sustainable. Future research should focus on overcoming data limitations, enhancing model interpretability, and exploring innovative AI approaches to contribute to the global fight against the HIV epidemic.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100080"},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial neural network guided optimization of tenofovir and Cyanovirin-N multipurpose preventive hydrogel formulation developed using the Box Behnken design model","authors":"Karamot O. Oyediran ,&nbsp;Ibilola M. Cardoso-Daodu ,&nbsp;Peace Ofonabasi Bassey ,&nbsp;Deborah A. Ogundemuren ,&nbsp;Ridwan Muhammed ,&nbsp;Olusola E. Ojo ,&nbsp;Andrew N. Amenaghawon ,&nbsp;Chukwuemeka P. Azubuike ,&nbsp;Rachna Agarwal ,&nbsp;Kondoru Haritha ,&nbsp;Margaret O. Ilomunaya","doi":"10.1016/j.pscia.2025.100079","DOIUrl":"10.1016/j.pscia.2025.100079","url":null,"abstract":"<div><div>Tenofovir (TNF) is an antiretroviral drug that has being used as a topical microbicide to prevent human immunodeficiency virus transmission (HIV). Cyanovirin-N (CV-N) is a lectin protein that can bind to the HIV envelope glycoprotein and inhibit viral entry. The combination of TNF and CV-N may have synergistic effects and enhance the efficacy of microbicide. The aim of this study was to develop and optimize composite hydrogel formulations containing 1%TNF and 0.0005% CV-N using Box Behnken Design. A three-factor, three-level Box-Behnken design was employed to investigate the effects of the concentrations of PEG₂₀₀₀, sodium carboxyl methylcellulose (NaCMC), and calcium chloride on the release of Tenofovir, flux, and mucoadhesion. The mucoadhesion was evaluated by measuring the percent mucin adsorption while flux and release kinetics were evaluated using the Franz cell diffusion method. The optimal hydrogel formulation was found to contain 4% NaCMC, 2% PEG2000 and 1% CaCl₂. The hydrogel had a pH of 4.5 ​± ​0.017, a viscosity of 275600 ​± ​0.65 ​cP, flux 9806 μg/cm²/h for TNF with a drug release of 119, 205.6 μg/cm². The TNF gel exhibited a pseudoplastic rheological behavior with 96.3% muco-adhesion. The study successfully developed an optimized TNF/CV-N mucoadhesive hydrogel, highlighting its potential as an on-demand multipurpose prevention technology (MPT) for HIV. The formulation was optimized to ensure good drug release, flux and mucoadhesion. The optimized hydrogel offers a convenient, effective method for preventing sexually transmitted infections (STIs), addressing critical challenges in drug delivery and user adherence while advancing public health strategies for STIs.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the CHJ01 antitumor activity and mechanism via targeting sphingosine kinase 1 in A549 cells","authors":"Caiyu Liu ,&nbsp;Shengmei Gao ,&nbsp;Bo Liu ,&nbsp;Feipeng Zhang ,&nbsp;Yanling Mu ,&nbsp;Fuwen Wang ,&nbsp;Yan Li","doi":"10.1016/j.pscia.2025.100077","DOIUrl":"10.1016/j.pscia.2025.100077","url":null,"abstract":"<div><div>The SphK1 inhibitor development is of great importance for the treatment of non-small cell lung cancer (NSCLC). In this study, CHJ01 which has been previously shown anti-tumor effects was introduced to investigate the detailed antitumor mechanism both <em>in</em> <em>vitro</em> and <em>in vivo</em>. CHJ01 inhibited the A549 ​cell proliferation, migration, and invasion significantly and showed cytotoxicity to A549. CHJ01 induced G0/G1 cell cycle arrest by increasing ceramide levels and altered the expression of TRAF2, Bcl-2, Bax and RELA. CHJ01 inhibited the TRAF2/NF-κB signaling pathway and promoted apoptosis by downregulating Bcl-2 and upregulating Bax. <em>In vivo</em> anti-tumor effects were investigated using a nude mouse ectopic tumor model. CHJ01 reduced the volumes and weights of xenograft tumor in nude mice. CHJ01 induced apoptosis by HE staining and immunohistochemistry assay. These results indicated that CHJ01 can be a potential candidate for the treatment of NSCLC.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assay development and screening of inhibitors targeting the SARS-CoV-2 2′-O-methyltransferase NSP16","authors":"Mengtong Cao ,&nbsp;Carl W. Trieshmann ,&nbsp;Subodh Kumar Samrat ,&nbsp;Hongmin Li ,&nbsp;Yifei Wu ,&nbsp;Steven P. Maher ,&nbsp;Angela A. Bae ,&nbsp;Zhong-Ru Xie ,&nbsp;Robert J. Hogan ,&nbsp;Y. George Zheng","doi":"10.1016/j.pscia.2025.100076","DOIUrl":"10.1016/j.pscia.2025.100076","url":null,"abstract":"<div><div>The coronavirus disease-2019 (COVID-19) pandemic, etiologically caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has profoundly impacted the global health. While vaccines have been developed, they have shown limited efficacy in treating patients already under infection or preventing infection with emerging SARS-CoV-2 variants. The nonstructural protein 16 (NSP16), with the assistance of the nonstructural protein 10 (NSP10), is responsible for forming the Cap-1 structure, which is critical for viral replication and immune evasion through the 5′-capping of viral mRNA. As a result, NSP16/NSP10 has emerged as a promising target for antiviral treatment of coronaviruses. In this study, we aimed to discover small molecule inhibitors of NSP16/NSP10 by leveraging recent structural insights and combined tools of virtual and experimental screenings. We designed a simple scintillation proximity assay to enable biochemical testing for NSP16/NSP10 enzymatic activity and applied it to screen inhibitors from candidate hit compounds that are derived from molecular docking-based virtual screenings. We identified potential hits that inhibit the NSP16 activity with cellular efficacy. Together with structural analysis and chemotype categorization, this study lays the groundwork for novel antiviral therapeutics development against SARS-CoV-2 and related coronaviruses.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100076"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent progress on formulations of hirudin","authors":"Zheng Bao ,&nbsp;Xingyu Qi ,&nbsp;Suling Zhu ,&nbsp;Mao Zhang ,&nbsp;Xinyue Liu ,&nbsp;Peidong Chen ,&nbsp;Li Zhang ,&nbsp;Ting Geng ,&nbsp;Fang-Fang Cheng","doi":"10.1016/j.pscia.2025.100078","DOIUrl":"10.1016/j.pscia.2025.100078","url":null,"abstract":"<div><div>Hirudin is an effective active ingredient derived from the salivary glands of leech. It is a small peptide molecule consisting of 65–66 amino acids and demonstrates a strong inhibitory effect on thrombin, providing beneficial anticoagulant and antithrombotic properties. However, as a biopharmaceutical peptide, it has some drawbacks such as easy degradation, short half-life, low bioavailability, and high risk of hemorrhage in clinical use. To overcome these challenges, various formulations were developed. In this work, a comprehensive review of research progress was provided in both traditional and novel hirudin formulations, spanning from lyophilized powders to biotechnology-based pharmaceuticals, covering various dosage forms to offer comprehensive references for field research. Firstly the advantages and limitations of conventional preparations were assessed such as freeze-dried powders, capsules, and injections. Then a detailed exploration of frontier strategies including nanotechnology-based delivery systems, transdermal formulations, and biotechnology-driven prodrug designs were conducted. This article aims to comprehensively analyze cutting-edge advancements in hirudin preparation research, providing updated information for relevant researchers by integrating traditional dosage optimization with breakthrough emerging technologies.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homologous tumor cell exosome-based drug delivery system co-delivering temozolomide and resveratrol for orthotopic glioblastoma therapy","authors":"Xuemei Wang ,&nbsp;Tao Zhang ,&nbsp;Dandan Zhang ,&nbsp;Yuxin Cao ,&nbsp;Xinxin Wang ,&nbsp;Xiaowei Liu ,&nbsp;Weili Yang ,&nbsp;Yingchao Liu ,&nbsp;Daquan Chen","doi":"10.1016/j.pscia.2025.100075","DOIUrl":"10.1016/j.pscia.2025.100075","url":null,"abstract":"<div><div>Temozolomide (TMZ) is the first-line chemotherapeutic agent for treating glioblastoma multiforme (GBM), but its potency is hampered by inevitable drug resistance and systematic toxicity. Novel strategies that can decrease drug-associated adverse events are urgently needed. Encouraged by the significant pro-apoptotic, anti-inflammatory, and anti-proliferative properties of resveratrol (RES), one of the most widely studied polyphenolic compounds in cancer therapy, we propose a synergistic therapeutic strategy by using the combination of TMZ and RES to inhibit GBM progression. Recently, exosomes (Exos) have received increasing attention as promising drug delivery alternatives with favorable intrinsic features. In this work, Exos derived from homologous U87 ​cells are developed to co-deliver TMZ/RES for GBM therapy, defined as U87-Exos@TMZ/RES. It is found that U87-Exos@TMZ/RES share various advantages, including intrinsic tumor-targeting accumulation with homologous effects, as well as enhanced antitumor activity with synergistic effects of TMZ and RES. Furthermore, the excellent therapeutic effect of U87-Exos@TMZ/RES is also achieved in orthotopic GBM models. Based on these results, this novel U87-Exos@TMZ/RES delivery platform can provide a promising systemic chemotherapy strategy for enhancing GBM treatment.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100075"},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D-pinitol modulates the anti-emetic effects of aprepitant, domperidone, and ondansetron in chicks","authors":"Md. Elit Rahman ,&nbsp;Md. Anisur Rahman ,&nbsp;Salehin Sheikh ,&nbsp;Md. Jannatul Islam Polash ,&nbsp;Sozoni Khatun ,&nbsp;Mst. Sonia Akter Bristi ,&nbsp;Md. Showkoth Akbor ,&nbsp;Mst. Farjanamul Haque ,&nbsp;Mehedi Hasan Bappi ,&nbsp;Tohidul Islam Tanim ,&nbsp;Siddique Akber Ansari ,&nbsp;Irfan Aamer Ansari ,&nbsp;Elaine Cristina Pereira Lucetti ,&nbsp;Carolina Bandeira Domiciano ,&nbsp;Henrique D.M. Coutinho ,&nbsp;Muhammad Torequl Islam","doi":"10.1016/j.pscia.2025.100073","DOIUrl":"10.1016/j.pscia.2025.100073","url":null,"abstract":"<div><div>Naturally occurring substance, D-pinitol (DPL) belongs to the significant inositol family has numerous pharmacological activity. In this study we evaluated the anti-emetic effect as well as modulation activities of DPL on the recent market drugs aprepitant (APR), domperidone (DOM), hyoscine butyl bromide (HYS), and ondansetron (ODN) on emesis in the chick model. To highlight the possible anti-emetic activity in copper sulfate induced emesis chick models, we use several reference drugs, such as APR (26 ​mg/kg), DOM (7 ​mg/kg), OND (5 ​mg/kg), and HYS (21 ​mg/kg), as positive controls, while the vehicles serve as negative controls. All reference drugs are given alone or in combined groups to evaluate their anti-emetic and modulation effects. The results suggest DPL (25 or 50 ​mg/kg) increases the mean number of latency in the chicks compared to vehicles, and the combination groups, DPL (25 ​mg/kg) showed better anti-emetic effects with DOM and ODN while DPL (50 ​mg/kg) reduces the number of retches compared to vehicles and combined drug therapy with reference drugs. Additionally, A variety of computational algorithms were used to visualise ligand–receptor interactions and quantify the binding affinities of DPL and other ligands towards the dopamine receptors (D2 and D3), muscarinic acetylcholine receptors (M1–M5), and serotonin receptor (5HT3). The molecular docking study indicated that DPL exhibits the highest binding affinity towards subtypes M2 (having a docking score of −5.7 ​kcal/mol) and D3 (having a docking score of −5.7 ​kcal/mol) in comparison to certain standards for these receptors, which have docking scores of DOM (−9.7 ​kcal/mol) and HYS (−7.1 ​kcal/mol) for M2 and D3, respectively. Our findings suggest that DPL has anti-emetic properties in chicks, possibly through interactions with the M2 and D3 receptor pathways.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100073"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The crucial role of SPP1 in osteoporosis, osteoarthritis, and cancer","authors":"Yaru Qu ,&nbsp;Shuixian Li ,&nbsp;Huiyuan Luo ,&nbsp;Junnan Li ,&nbsp;Tong Wang ,&nbsp;Xiuzhen Han","doi":"10.1016/j.pscia.2025.100074","DOIUrl":"10.1016/j.pscia.2025.100074","url":null,"abstract":"<div><div>Osteopontin (OPN), also known as secreted phosphoprotein 1(SPP1), is a highly glycosylated and phosphorylated acidic protein, which is a multifunctional glycoprotein expressed in numerous cell types. SPP1 is involved in the attachment of osteoclasts to mineralized bone matrix, inflammatory reaction, cell recruitment, and tissue repair, and plays an important role in bone formation, fibrosis, immune diseases, and cancer. The role of SPP1 in osteoporosis, osteoarthritis and cancer is multi-faceted. While it holds potential therapeutic value, it also presents certain limitations. This review integrates the molecular structural characteristics of SPP1, including isoform variants and post-translational modifications, with its pathophysiological functions. It highlights the regulatory roles of SPP1 in these diseases: maintaining the dynamic balance between bone resorption and formation in osteoporosis, promoting cartilage degeneration and inflammation in osteoarthritis, and driving tumor progression in cancer through the activation of pathways such as PI3K/AKT/mTOR. Furthermore, SPP1 regulates tumor-associated macrophages and fibroblasts within the tumor microenvironment, thereby facilitating immune evasion and metastasis. The article also underscores the potential value of precisely modulating SPP1 activity in the treatment of osteoporosis and osteoarthritis and suggests a combined therapeutic strategy targeting SPP1, offering novel insights into overcoming the limitations of single-target cancer therapies.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100074"},"PeriodicalIF":0.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLDC interacts with VPS34 to inhibit tumorigenesis and epithelial-mesenchymal transition in hepatocellular carcinoma","authors":"Zan Song ,&nbsp;Hao Dong ,&nbsp;Kailing Zhang ,&nbsp;Bingke Qiao ,&nbsp;Leilei Li ,&nbsp;Zhicheng Zhang ,&nbsp;Zhili Fan ,&nbsp;Jing Li ,&nbsp;Yu Li ,&nbsp;Mengfei Liu ,&nbsp;Ying Liu ,&nbsp;Xinyu Gu ,&nbsp;Tao Zhang","doi":"10.1016/j.pscia.2025.100072","DOIUrl":"10.1016/j.pscia.2025.100072","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer with high mortality and limited therapeutic strategy. Glycine decarboxylase (GLDC) is the key limiting enzyme in glycine breakdown metabolism and acts as oncogene or tumor suppressor to impact tumor onset and progression in a context dependent manner. However, the underlying mechanism of GLDC on autophagy and progression is largely unexplored in HCC. Here, we showed that GLDC overexpression inhibited cell proliferation, cell migration and promoted cell senescence and autophagy in HCC. Intriguingly, induced GLDC remarkably attenuated epithelial-mesenchymal transition (EMT) progress and tumor growth <em>in vitro</em> and <em>in vivo</em>. Mechanically, we demonstrated that GLDC upregulated VPS34 protein and enhanced its interaction with VPS34, thus promoting the association of VPS34 with Beclin1/ATG14 complex and autophagy induction in HCC. Importantly, GLDC acetylation at K514 promoted interaction of GLDC-VPS34, whereas GLDC acetylation-dead mutant K514R abolished their binding. Furthermore, GLDC protein was decreased in HCC tissues compared with para-tumor tissues and reduced GLDC was significantly correlated with poor prognosis of patients. In conclusion, we unveil the key regulatory role of GLDC in autophagy and HCC progression through VPS34 and provide a potential strategy for HCC therapy.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100072"},"PeriodicalIF":0.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of glutarimide-containing polyketides: Structures, bioactivities and their biosynthesis","authors":"Yanrong Shi ,&nbsp;Chunhua Lu ,&nbsp;Yuemao Shen","doi":"10.1016/j.pscia.2025.100071","DOIUrl":"10.1016/j.pscia.2025.100071","url":null,"abstract":"<div><div>Glutarimide-containing polyketides (GPs) are an important class of natural products with antifungal, antibacterial, antitumor and other biological activities. Generally, the structures have a six-membered ring of glutarimide (also known as 2,6-piperidinedione) and a polyketide side chain or a ring of varying lengths attached at C4 such as cycloheximide, 9-methylstreptimidone and migrastatin. Currently, at least 65 natural glutarimide antibiotics have been isolated and identified. The novel biosynthetic mechanism of the <em>trans</em>-AT PKS and multifaceted modes of action have promoted the progressive exploration of glutarimide-containing products. However, the related information on the aspects of new structure discovery, biological activity and biosynthesis of GPs is still not available. This review summarizes the current research from the aspects of new structure discovery, biological activity and biosynthesis, aiming to provide a reference for in-depth products mining and structure-activity relationship research. Special emphasis is placed on their potential as drug leads, particularly in cancer therapy, and the role of modern analytical techniques in their discovery and characterization.</div></div>","PeriodicalId":101012,"journal":{"name":"Pharmaceutical Science Advances","volume":"3 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}