Pub Date : 2026-01-08DOI: 10.1016/j.drudis.2026.104599
Monong Zhao , Wenjing Liu , Wenjia Lu , Zhiyu Li , Hongxi Wu
Antibody–drug conjugates (ADCs) have revolutionized breast cancer (BC) therapy, yet their efficacy is limited by resistance. With advances in ADC technology, broader paradigms of next-generation drug conjugates have emerged. For BC treatment, emerging drug conjugates under current clinical trials include degrader–antibody conjugates, antibody–oligonucleotide conjugates, immune-stimulating antibody conjugates, small molecule–drug conjugates, and peptide–drug conjugates. These agents exhibit significant potential in the treatment of BC and in bypassing ADC common resistance pathways through novel molecular mechanisms or delivery pathways. In this review, we elucidate the structures and mechanisms of these emerging drug conjugates, summarize their latest research progress, and analyze their potential to overcome ADC resistance, aiming to contribute to the development of drug conjugates in the future.
{"title":"Next-generation drug conjugates for breast cancer: Clinical prospects and mechanism-based strategies to overcome resistance","authors":"Monong Zhao , Wenjing Liu , Wenjia Lu , Zhiyu Li , Hongxi Wu","doi":"10.1016/j.drudis.2026.104599","DOIUrl":"10.1016/j.drudis.2026.104599","url":null,"abstract":"<div><div>Antibody–drug conjugates (ADCs) have revolutionized breast cancer (BC) therapy, yet their efficacy is limited by resistance. With advances in ADC technology, broader paradigms of next-generation drug conjugates have emerged. For BC treatment, emerging drug conjugates under current clinical trials include degrader–antibody conjugates, antibody–oligonucleotide conjugates, immune-stimulating antibody conjugates, small molecule–drug conjugates, and peptide–drug conjugates. These agents exhibit significant potential in the treatment of BC and in bypassing ADC common resistance pathways through novel molecular mechanisms or delivery pathways. In this review, we elucidate the structures and mechanisms of these emerging drug conjugates, summarize their latest research progress, and analyze their potential to overcome ADC resistance, aiming to contribute to the development of drug conjugates in the future.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 2","pages":"Article 104599"},"PeriodicalIF":7.5,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948239","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}
Pub Date : 2026-01-06DOI: 10.1016/j.drudis.2026.104598
Xinlan Hu , Yan Wu , Qingsong Chen , Zhuo Chen , Qianbin Li
Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation. Emerging evidence implicates ferroptosis in the pathogenesis of various kidney diseases by inducing death in renal tubular epithelial cells (RTECs), podocytes, mesangial cells (MCs), and endothelial cells (ECs), which exhibit distinct structural and functional traits that might determine their differential susceptibility to ferroptosis. Despite its importance, the precise mechanism of ferroptosis in kidney pathology remains unclear, limiting its therapeutic potential and drug development. Understanding cell type-specific ferroptosis mechanisms and their spatial distribution in kidney diseases could provide novel insights for renal protection. In this review, we summarize current knowledge regarding ferroptosis susceptibility in different renal cell types to bridge cellular and organ-level perspectives for potential translational applications.
{"title":"Insights into the cell type-specific susceptibility of kidney cells to ferroptosis","authors":"Xinlan Hu , Yan Wu , Qingsong Chen , Zhuo Chen , Qianbin Li","doi":"10.1016/j.drudis.2026.104598","DOIUrl":"10.1016/j.drudis.2026.104598","url":null,"abstract":"<div><div>Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation. Emerging evidence implicates ferroptosis in the pathogenesis of various kidney diseases by inducing death in renal tubular epithelial cells (RTECs), podocytes, mesangial cells (MCs), and endothelial cells (ECs), which exhibit distinct structural and functional traits that might determine their differential susceptibility to ferroptosis. Despite its importance, the precise mechanism of ferroptosis in kidney pathology remains unclear, limiting its therapeutic potential and drug development. Understanding cell type-specific ferroptosis mechanisms and their spatial distribution in kidney diseases could provide novel insights for renal protection. In this review, we summarize current knowledge regarding ferroptosis susceptibility in different renal cell types to bridge cellular and organ-level perspectives for potential translational applications.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 2","pages":"Article 104598"},"PeriodicalIF":7.5,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931736","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}
Pub Date : 2026-01-01DOI: 10.1016/j.drudis.2025.104578
Linjie Wang , Eric Parolin , Zoey Chopra , Garth W Strohbehn
Oncology is the biopharmaceutical industry’s most active area for mergers and acquisitions (M&A) activity, reflecting both the scientific innovation and economics of precision medicines in the modern context. This review characterizes trends in 151 publicly disclosed pharmaceutical oncology M&A transactions between 2000 and 2019, showing that oncology dealmaking is increasingly concentrated among a small group of acquirers, that the bulk of acquisitions are of assets that are early in their development, and that deal structures increasingly emphasize milestone-linked and deferred payments. Together, these trends reveal how regulatory incentives, macroeconomic conditions, and productivity challenges have reshaped the scale and structure of oncology M&A in the precision-medicine era.
{"title":"Oncology pharmaceutical mergers and acquisitions activity in the precision medicine era","authors":"Linjie Wang , Eric Parolin , Zoey Chopra , Garth W Strohbehn","doi":"10.1016/j.drudis.2025.104578","DOIUrl":"10.1016/j.drudis.2025.104578","url":null,"abstract":"<div><div>Oncology is the biopharmaceutical industry’s most active area for mergers and acquisitions (M&A) activity, reflecting both the scientific innovation and economics of precision medicines in the modern context. This review characterizes trends in 151 publicly disclosed pharmaceutical oncology M&A transactions between 2000 and 2019, showing that oncology dealmaking is increasingly concentrated among a small group of acquirers, that the bulk of acquisitions are of assets that are early in their development, and that deal structures increasingly emphasize milestone-linked and deferred payments. Together, these trends reveal how regulatory incentives, macroeconomic conditions, and productivity challenges have reshaped the scale and structure of oncology M&A in the precision-medicine era.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 1","pages":"Article 104578"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145719982","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}
Pub Date : 2026-01-01DOI: 10.1016/j.drudis.2025.104581
Hui Yan , Gao-Min Liu , Xiang Li , Meng-Shuang Zhao , Jia-Bin Li , Ya-Sheng Li
Bacterial resistance to antibiotics is increasing, seriously threatening human health; thus, the search for alternatives to antibiotics has become a significant research focus. Antimicrobial metals have long been used for their therapeutic properties, and different metals have specific antimicrobial mechanisms of action. Gallium shows broad antibacterial activity in vitro and in vivo, as well as synergistic antibacterial activity with other drugs, highlighting its potential clinical application for the treatment of infectious diseases. Here, we review research into the antimicrobial effects and mechanisms of action of gallium ions, as well as the clinical application of gallium ion-related drugs. Our review provides a theoretical reference for the application of the antimicrobial properties of gallium ions in clinical treatment.
{"title":"Gallium-based antimicrobials: mechanisms of action, resistance outlook, and translational potential for next-generation anti-infective therapies","authors":"Hui Yan , Gao-Min Liu , Xiang Li , Meng-Shuang Zhao , Jia-Bin Li , Ya-Sheng Li","doi":"10.1016/j.drudis.2025.104581","DOIUrl":"10.1016/j.drudis.2025.104581","url":null,"abstract":"<div><div>Bacterial resistance to antibiotics is increasing, seriously threatening human health; thus, the search for alternatives to antibiotics has become a significant research focus. Antimicrobial metals have long been used for their therapeutic properties, and different metals have specific antimicrobial mechanisms of action. Gallium shows broad antibacterial activity <em>in vitro</em> and <em>in vivo</em>, as well as synergistic antibacterial activity with other drugs, highlighting its potential clinical application for the treatment of infectious diseases. Here, we review research into the antimicrobial effects and mechanisms of action of gallium ions, as well as the clinical application of gallium ion-related drugs. Our review provides a theoretical reference for the application of the antimicrobial properties of gallium ions in clinical treatment.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 1","pages":"Article 104581"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740431","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}
Pub Date : 2026-01-01DOI: 10.1016/j.drudis.2025.104591
Guillermo Aquino-Jarquin
Glycosylated RNAs (glycoRNAs) have recently emerged as an unexpected class of RNA–glycan hybrids, expanding the chemical and functional landscape of the transcriptome. Their covalent glycan modifications confer molecular features typically reserved for glycoproteins and glycolipids. Notably, proximity ligation studies demonstrate that glycoRNAs reside on the cell surface, overturning the long-standing paradigm that RNAs function exclusively inside cells. This extracellular localization suggests that glycoRNAs engage membrane lectins, immune receptors, and signaling complexes with regulatory consequences distinct from canonical RNA biology. These discoveries position glycoRNAs as previously unrecognized mediators of intercellular communication, immune tuning, and tumor-associated signaling.
{"title":"Emerging cell surface glycoRNAs with potential regulatory roles","authors":"Guillermo Aquino-Jarquin","doi":"10.1016/j.drudis.2025.104591","DOIUrl":"10.1016/j.drudis.2025.104591","url":null,"abstract":"<div><div>Glycosylated RNAs (glycoRNAs) have recently emerged as an unexpected class of RNA–glycan hybrids, expanding the chemical and functional landscape of the transcriptome. Their covalent glycan modifications confer molecular features typically reserved for glycoproteins and glycolipids. Notably, proximity ligation studies demonstrate that glycoRNAs reside on the cell surface, overturning the long-standing paradigm that RNAs function exclusively inside cells. This extracellular localization suggests that glycoRNAs engage membrane lectins, immune receptors, and signaling complexes with regulatory consequences distinct from canonical RNA biology. These discoveries position glycoRNAs as previously unrecognized mediators of intercellular communication, immune tuning, and tumor-associated signaling.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 1","pages":"Article 104591"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145831854","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}
Exosomes are nanoscale extracellular vesicles that mediate critical intercellular communication within the tumor microenvironment (TME). Recent advancements reveal that exosome populations within tumors are not uniform but exhibit significant heterogeneity in their molecular cargo and functional output. This heterogeneity is particularly pronounced in spatially organized tumors, where distinct functional zones, driven by gradients in local stress, perfusion, and metabolic states, orchestrate the release of unique exosome subtypes. These functional zones include stromal, hypoxic, perivascular, quiescent, and immune-cold regions. The zone-specific exosomes deliver specialized molecular cargos, including nucleic acids, proteins, lipids, and metabolites, to recipient cells within the TME and at distant sites. This communication promotes tumor sustenance and contributes to drug resistance through diverse mechanisms, such as immune suppression, epithelial–mesenchymal transition (EMT), metabolic reprogramming, and the activation of prosurvival signaling pathways. Although bulk exosome analysis has enabled the development of biomarkers for personalized medicine, it often fails to capture these intricate, zone-specific influences. This review explores emerging techniques, including single-cell sequencing, microchip-based 3D tumor cultures, advanced spectroscopic methods, and spatial biology platforms, that are poised to elucidate the spatiotemporal communication networks mediated by zonal exosomes, thereby advancing the understanding of drug resistance mechanisms.
{"title":"Exosomal heterogeneity and functional zonation in cancer drug resistance","authors":"Shikshya Swarupa Panda, Rajeev Kumar Sahoo, Sambit Kumar Patra, Sachidananda Behera, Ashish Kumar Khamari, Bijesh Kumar Biswal","doi":"10.1016/j.drudis.2025.104587","DOIUrl":"10.1016/j.drudis.2025.104587","url":null,"abstract":"<div><div>Exosomes are nanoscale extracellular vesicles that mediate critical intercellular communication within the tumor microenvironment (TME). Recent advancements reveal that exosome populations within tumors are not uniform but exhibit significant heterogeneity in their molecular cargo and functional output. This heterogeneity is particularly pronounced in spatially organized tumors, where distinct functional zones, driven by gradients in local stress, perfusion, and metabolic states, orchestrate the release of unique exosome subtypes. These functional zones include stromal, hypoxic, perivascular, quiescent, and immune-cold regions. The zone-specific exosomes deliver specialized molecular cargos, including nucleic acids, proteins, lipids, and metabolites, to recipient cells within the TME and at distant sites. This communication promotes tumor sustenance and contributes to drug resistance through diverse mechanisms, such as immune suppression, epithelial–mesenchymal transition (EMT), metabolic reprogramming, and the activation of prosurvival signaling pathways. Although bulk exosome analysis has enabled the development of biomarkers for personalized medicine, it often fails to capture these intricate, zone-specific influences. This review explores emerging techniques, including single-cell sequencing, microchip-based 3D tumor cultures, advanced spectroscopic methods, and spatial biology platforms, that are poised to elucidate the spatiotemporal communication networks mediated by zonal exosomes, thereby advancing the understanding of drug resistance mechanisms.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 1","pages":"Article 104587"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792882","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}
Pub Date : 2026-01-01DOI: 10.1016/j.drudis.2025.104590
Zi-Xian Liao , S.-Ja Tseng
Tumors evolve in tandem with their tumor microenvironment (TME), often creating an immunosuppressive state that hinders anticancer responses. Whereas antitumor immunostimulating cytokines can reverse this suppression and trigger effective immunity, their systemic administration causes severe toxicity, limiting their clinical use. mRNA technology, recognized as a medical breakthrough highlighted by COVID-19 vaccines, offers a promising approach. This review posits that local delivery of mRNA-encoded antitumor cytokines to the TME enables targeted, in situ production, maximizing antitumor effects while minimizing systemic toxicity.
{"title":"Evaluating the potential of mRNA technology for cytokine production and delivery in antitumor therapy","authors":"Zi-Xian Liao , S.-Ja Tseng","doi":"10.1016/j.drudis.2025.104590","DOIUrl":"10.1016/j.drudis.2025.104590","url":null,"abstract":"<div><div>Tumors evolve in tandem with their tumor microenvironment (TME), often creating an immunosuppressive state that hinders anticancer responses. Whereas antitumor immunostimulating cytokines can reverse this suppression and trigger effective immunity, their systemic administration causes severe toxicity, limiting their clinical use. mRNA technology, recognized as a medical breakthrough highlighted by COVID-19 vaccines, offers a promising approach. This review posits that local delivery of mRNA-encoded antitumor cytokines to the TME enables targeted, <em>in situ</em> production, maximizing antitumor effects while minimizing systemic toxicity.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 1","pages":"Article 104590"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145792805","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}
Pub Date : 2026-01-01DOI: 10.1016/j.drudis.2026.104596
Charles H. Jones , Marie Beitelshees
Highly pathogenic avian influenza A (H5N1) clade 2.3.4.4b is now widespread in US birds and has spilled over into mammals, raising concern about pandemic emergence. We applied the Viral Trait Assessment for Pandemics (ViTAP) model to score 11 intrinsic viral traits using a structured literature review, expert elicitation, and sensitivity analyses. The resulting composite score for contemporary US H5N1 was 3.28/5 (moderate–high risk); transmission-related traits contributed most to score uncertainty, while the absence of sustained human–human spread currently limits risk. Thus, ViTAP provides a transparent way to prioritize surveillance, countermeasure development, and preparedness as H5N1 continues to evolve.
{"title":"Trait-based ViTAP assessment of pandemic potential for US avian influenza A (H5N1) clade 2.3.4.4b","authors":"Charles H. Jones , Marie Beitelshees","doi":"10.1016/j.drudis.2026.104596","DOIUrl":"10.1016/j.drudis.2026.104596","url":null,"abstract":"<div><div>Highly pathogenic avian influenza A (H5N1) clade 2.3.4.4b is now widespread in US birds and has spilled over into mammals, raising concern about pandemic emergence. We applied the Viral Trait Assessment for Pandemics (ViTAP) model to score 11 intrinsic viral traits using a structured literature review, expert elicitation, and sensitivity analyses. The resulting composite score for contemporary US H5N1 was 3.28/5 (moderate–high risk); transmission-related traits contributed most to score uncertainty, while the absence of sustained human–human spread currently limits risk. Thus, ViTAP provides a transparent way to prioritize surveillance, countermeasure development, and preparedness as H5N1 continues to evolve.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 1","pages":"Article 104596"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931738","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}
Achieving precise control over anticancer drug activity remains a key challenge in prodrug design. Stimuli-responsive systems address this limitation by enabling selective drug release within the tumor microenvironment. Among them, externally activated prodrugs (triggered by light, ionizing radiation, or ultrasound) offer superior spatial and temporal precision, with minimal systemic toxicity. This review critically examines recent advances in design strategies, activation mechanisms, and the translational potential of these systems, including both organic photocages and emerging metal-based platforms [e.g. Pt(IV) and Ru(II) complexes]. Particular attention is given to their integration with next-generation therapeutic modalities such as proteolysis-targeting chimeras (PROTACs) and antibody–drug conjugates (ADCs). Externally triggered prodrug technologies are poised to redefine precision oncology by improving efficacy, safety, and on-demand activation from molecular design to preclinical validation.
{"title":"Spatiotemporal control of prodrug activation through external stimuli for effective and safe on-site release in solid tumors: From current advances to future perspectives","authors":"Gabriele La Monica , Alessia Bono , Federica Alamia , Antonino Lauria , Annamaria Martorana","doi":"10.1016/j.drudis.2025.104595","DOIUrl":"10.1016/j.drudis.2025.104595","url":null,"abstract":"<div><div>Achieving precise control over anticancer drug activity remains a key challenge in prodrug design. Stimuli-responsive systems address this limitation by enabling selective drug release within the tumor microenvironment. Among them, externally activated prodrugs (triggered by light, ionizing radiation, or ultrasound) offer superior spatial and temporal precision, with minimal systemic toxicity. This review critically examines recent advances in design strategies, activation mechanisms, and the translational potential of these systems, including both organic photocages and emerging metal-based platforms [e.g. Pt(IV) and Ru(II) complexes]. Particular attention is given to their integration with next-generation therapeutic modalities such as proteolysis-targeting chimeras (PROTACs) and antibody–drug conjugates (ADCs). Externally triggered prodrug technologies are poised to redefine precision oncology by improving efficacy, safety, and on-demand activation from molecular design to preclinical validation.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 1","pages":"Article 104595"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145909532","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}
Drug discovery is still an expensive and time-consuming enterprise, a majority of clinical trial failures being traced to inaccurate predictions of molecular properties. To address this challenge, a new technique: fine-tuning transformer-based model ChemBERTa, is presented to achieve an accurate molecular property prediction. The hybrid architecture outperforms traditional networks, such as MolBERT, by combining ChemBERTa and graph neural networks. This superiority is supported by statistical tests, and the effectiveness of this model on systems of complex chemical structures is proved by the systematic error analysis. The technique proves effective on pharmaceutical and non-pharmaceutical compounds alike in the pesticide sector. This approach underlines the ability of AI to help and improve efficacy in drug discovery, lower the cost and improve clinical success rates.
{"title":"Transformers in drug discovery: fine-tuning ChemBERTa for high-accuracy prediction of solubility, toxicity and binding affinity","authors":"Sandhya Alagarsamy , Chin-Shiuh Shieh , Mong-Fong Horng , Subhashini Radhakrishnan , Sethuraman Radhakrishnan , Abdelwahab Omri","doi":"10.1016/j.drudis.2026.104602","DOIUrl":"10.1016/j.drudis.2026.104602","url":null,"abstract":"<div><div>Drug discovery is still an expensive and time-consuming enterprise, a majority of clinical trial failures being traced to inaccurate predictions of molecular properties. To address this challenge, a new technique: fine-tuning transformer-based model ChemBERTa, is presented to achieve an accurate molecular property prediction. The hybrid architecture outperforms traditional networks, such as MolBERT, by combining ChemBERTa and graph neural networks. This superiority is supported by statistical tests, and the effectiveness of this model on systems of complex chemical structures is proved by the systematic error analysis. The technique proves effective on pharmaceutical and non-pharmaceutical compounds alike in the pesticide sector. This approach underlines the ability of AI to help and improve efficacy in drug discovery, lower the cost and improve clinical success rates.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"31 1","pages":"Article 104602"},"PeriodicalIF":7.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984272","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}
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