Expert Opinion on Drug Discovery最新文献_第5页

Are patient-derived models of amyotrophic lateral sclerosis a game changer for novel drug discovery? 肌萎缩性侧索硬化症患者衍生模型是新药发现的游戏规则改变者吗？

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-07-01 Epub Date: 2026-06-23 DOI: 10.1080/17460441.2026.2689746

Satoru Morimoto, Hideyuki Okano

{"title":"Are patient-derived models of amyotrophic lateral sclerosis a game changer for novel drug discovery?","authors":"Satoru Morimoto, Hideyuki Okano","doi":"10.1080/17460441.2026.2689746","DOIUrl":"10.1080/17460441.2026.2689746","url":null,"abstract":"Introduction: ALS drug discovery has long depended on model systems that incompletely capture human disease heterogeneity, aging, and TDP-43 proteinopathy. Patient-derived platforms have therefore emerged as increasingly important human-relevant complements to animal and molecular models.Areas covered: This Critical Perspective examines when patient-derived ALS models genuinely change therapeutic decision-making rather than merely add mechanistic insight. The authors then propose a heuristic framework based on disease-relevant phenotype recapitulation, capture of patient-to-patient heterogeneity, and generation of findings that influence therapeutic prioritization or clinical translation. Furthermore, the authors evaluate iPSC-derived motor neurons, directly reprogrammed neurons, glial co-cultures, organoids, neural networks, and organ-chip systems against these conditions, while also addressing aging fidelity, reproducibility, upper motor neuron modeling, and regulatory implementation.Expert opinion: Patient-derived models are not yet standalone decision-grade tools for ALS drug development. Their present value lies in functioning as a human-biology filter for target discovery, reverse translation, biomarker development, and patient stratification when used within rigorous, standardized, and clinically linked workflows. The strongest current evidence supports proof-of-principle rather than generalized predictive validity.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"753-760"},"PeriodicalIF":7.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307890","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}

引用次数: 0

High-throughput screening assays for novel antibacterial identification: current advances and future prospects. 新型抗菌药物鉴定的高通量筛选方法：现状与展望。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-07-01 Epub Date: 2026-05-31 DOI: 10.1080/17460441.2026.2679706

Holly E E Floyd, Michelle Novais de Paula, Tanuka Sen, Angela M Kavanagh, Johannes Zuegg, Mark A T Blaskovich

{"title":"High-throughput screening assays for novel antibacterial identification: current advances and future prospects.","authors":"Holly E E Floyd, Michelle Novais de Paula, Tanuka Sen, Angela M Kavanagh, Johannes Zuegg, Mark A T Blaskovich","doi":"10.1080/17460441.2026.2679706","DOIUrl":"10.1080/17460441.2026.2679706","url":null,"abstract":"Introduction: High-throughput screening (HTS) has been central to antibacterial drug discovery for decades, identifying active compounds from large libraries. Advances in screening methodologies and compound availability have extended HTS from large organizations to smaller biotech and academic groups. Despite increased screening, the antibacterial pipeline remains insufficient to address growing antibiotic resistance, partly because screening conditions poorly replicate true infective environments.Area covered: This review summarizes HTS applications for novel antibacterial discovery, outlining standard techniques and practical limitations, highlighting emerging in vivo and intermediate-throughput in vitro methods developed to better reflect infection conditions. References were collected using PubMed and Google Scholar searches covering antibacterial HTS methodologies, focusing on the last 15 years but including earlier seminal publications where appropriate.Expert opinion: Antibacterial HTS traditionally relies on standard growth inhibition assays using reference isolates grown in nutrient-rich media. Although their outcome is informative, these conditions may not represent disease environments accurately enough to provide drug candidates with a high likelihood for translational success.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"803-817"},"PeriodicalIF":7.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148137040","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}

引用次数: 0

The preclinical discovery and development of acalabrutinib for the treatment of mantle cell lymphoma. 阿卡拉布替尼治疗套细胞淋巴瘤的临床前发现和开发。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-07-01 Epub Date: 2026-06-15 DOI: 10.1080/17460441.2026.2684645

Tadeusz Robak, Paweł Robak

{"title":"The preclinical discovery and development of acalabrutinib for the treatment of mantle cell lymphoma.","authors":"Tadeusz Robak, Paweł Robak","doi":"10.1080/17460441.2026.2684645","DOIUrl":"10.1080/17460441.2026.2684645","url":null,"abstract":"Introduction: Over the past decade, Bruton's tyrosine kinase (BTK) inhibitors have been approved for clinical use in several indolent B-cell lymphoid malignancies, including mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström macroglobulinemia. Among these, acalabrutinib is a second-generation covalent, irreversible BTK inhibitor that demonstrates higher selectivity and non-inferior efficacy than ibrutinib.Areas covered: This paper reviews recent developments in the use of acalabrutinib in treatment-naïve and relapsed/refractory mantle cell lymphoma (MCL). Google Scholar and PubMed were initially searched for articles in English, published from 2017 to February 2026. The reference lists of the articles were then searched again. In addition, a manual search was performed of conference proceedings from the last 5 years of The American Society of Hematology, American Society of Clinical Oncology and the European Hematology Association.Expert opinion: Acalabrutinib is approved by FDA for the treatment of previously treated and relapsed/refractory patients with MCL. While it has been found to demonstrate high activity and good tolerability as a single drug and in combination with other agents, further clinical trials are required to optimize its use in MCL and other lymphomas.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"729-739"},"PeriodicalIF":7.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148250014","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}

引用次数: 0

"Too soon to tell"? The potential of tools like AggrescanAI for novel drug discovery and development. “现在下结论还太早”？像侵略者ai这样的工具在新药发现和开发方面的潜力。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-07-01 Epub Date: 2026-06-09 DOI: 10.1080/17460441.2026.2686257

Cristina Marino-Buslje, Salvador Ventura

引用次数: 0

Moving forward with molecular skeleton editing (MSE) for new drug discovery: where to next? 分子骨架编辑（MSE）用于新药发现：下一步该做什么？

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-07-01 Epub Date: 2026-06-07 DOI: 10.1080/17460441.2026.2684438

Anthony J Burke, Carolina S Marques

{"title":"Moving forward with molecular skeleton editing (MSE) for new drug discovery: where to next?","authors":"Anthony J Burke, Carolina S Marques","doi":"10.1080/17460441.2026.2684438","DOIUrl":"10.1080/17460441.2026.2684438","url":null,"abstract":"Introduction: Molecular Skeleton Editing has emerged as a powerful strategy in medicinal chemistry, gaining significant attention over the past decade for its ability to rapidly access structurally diverse molecules. This approach encompasses the substitution, deletion and insertion of atoms within molecular frameworks, often resulting in ring expansion or contraction. From a drug discovery perspective, these transformations enable the direct conversion of core scaffolds into bioisosteric analogues while preserving substitution patterns, providing an efficient route to optimize biological and physicochemical properties.Areas covered: This review focuses on molecular editing approaches relevant to drug discovery that involve single-atom substitution, deletion or insertion, leading to skeletal modifications of cyclic frameworks. Representative examples highlighting the synthesis of therapeutically relevant compounds through these methodologies will be discussed. Peripheral editing, skeletal recasting, stereochemical editing, and functional group transpositions are beyond the scope of this review.Expert opinion: Recent advances demonstrate the considerable potential of molecular skeletal editing to accelerate lead optimization by enabling direct scaffold diversification from existing drugs and natural products, avoiding de novo synthesis. Despite these advances, important challenges remain, particularly the extension of editing methodologies to saturated sp³-rich systems and the development of stereoselective processes that preserve or generate optically pure products.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"741-751"},"PeriodicalIF":7.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197963","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}

引用次数: 0

Unfolding prion misfolding and the challenge of identifying effective therapeutics: is there hope on the horizon? 揭示朊病毒错误折叠和确定有效治疗方法的挑战：是否有希望？

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-07-01 Epub Date: 2026-06-19 DOI: 10.1080/17460441.2026.2688321

Sanaz Sabzehei, Nicole Innocenti, Marta Rigoli, Jesús R Requena, Emiliano Biasini

{"title":"Unfolding prion misfolding and the challenge of identifying effective therapeutics: is there hope on the horizon?","authors":"Sanaz Sabzehei, Nicole Innocenti, Marta Rigoli, Jesús R Requena, Emiliano Biasini","doi":"10.1080/17460441.2026.2688321","DOIUrl":"10.1080/17460441.2026.2688321","url":null,"abstract":"Introduction: Prion diseases are rare, fatal neurodegenerative disorders caused by the conformational conversion of cellular prion protein (PrP) into a pathogenic counterpart called PrPSc, that replicates by templated misfolding. The resulting misfolding cascade leads to synaptic failure and neuronal loss. Despite major advances in understanding prion structure and biology, no therapies exist. The mechanism of prion propagation challenges conventional drug discovery, limiting targets. Small molecules, immunotherapies, and gene silencing, have shown limited clinical success. Increasingly, research is shifting toward alternative strategies to modulate proteostasis, enhance clearance, or target transient folding and misfolding intermediates of PrP, offering new therapeutic opportunities. However, these emerging strategies remain at an early conceptual or preclinical stage, and significant translational hurdles remain.Areas covered: This chapter reviews prion drug discovery through the lens of PrP energy landscape. It summarizes efforts to target PrP conversion and highlights emerging approaches focused on degradation and intermediate targeting. Advances in structural biology and computational modelling are discussed as tools to identify novel therapeutic vulnerabilities.Expert opinion: The persistent failure of conventional strategies underscores the need for innovative approaches. Targeting transient conformational intermediates and exploiting cellular quality-control systems may redefine druggability in prion diseases and open new avenues for effective intervention.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"793-801"},"PeriodicalIF":7.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276787","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}

引用次数: 0

Why is it so difficult to discover drugs for amyotrophic lateral sclerosis? A protein intrinsic disorder perspective. 为什么发现治疗肌萎缩性侧索硬化症的药物如此困难？蛋白质内在失调的观点。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-06-01 Epub Date: 2026-03-24 DOI: 10.1080/17460441.2026.2648612

Vladimir N Uversky

{"title":"Why is it so difficult to discover drugs for amyotrophic lateral sclerosis? A protein intrinsic disorder perspective.","authors":"Vladimir N Uversky","doi":"10.1080/17460441.2026.2648612","DOIUrl":"10.1080/17460441.2026.2648612","url":null,"abstract":"Introduction: Amyotrophic Lateral Sclerosis (ALS) is the most common adult motor neuron disease, now viewed as a spectrum disorder rather than a single entity. Because of the significant person-to-person variability in the disease's biology, driven by both genetic and environmental interactions, finding a single \"magic bullet\" drug is unlikely. Despite decades of research, only a few ALS drugs have being developed. Drug discovery has a 95% failure rate due to genetic complexity, lack of sensitive biomarkers, diagnostic delays, inadequate animal models, and poor clinical trial design.Areas covered: This article considers several aspects related to the prevalence of intrinsic disorder in ALS-related proteins and highlights how these features might hinder rational structure-based drug discovery.Expert opinion: There is a common oversight in current drug discovery methodologies, which is the neglect of intrinsically disordered proteins (IDPs) playing several crucial roles in the pathology of neurodegeneration in general and ALS in particular. Therefore, it seems that the 'one-size-fits-all' approach to ALS is hitting a wall because these 'shapeshifters' of the cellular world are ignored. Consequently, to be more successful in finding drugs treating ALS, gears should be shifted from rational structure-based models to intrinsic disorder-centric approaches.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"553-573"},"PeriodicalIF":7.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510939","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}

引用次数: 0

Multi-target approaches to prion disease drug discovery: a status update. 朊病毒疾病的多靶点方法药物发现：现状更新。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-06-01 Epub Date: 2026-05-05 DOI: 10.1080/17460441.2026.2667912

Lea Nikolić, Giuseppe Legname

{"title":"Multi-target approaches to prion disease drug discovery: a status update.","authors":"Lea Nikolić, Giuseppe Legname","doi":"10.1080/17460441.2026.2667912","DOIUrl":"10.1080/17460441.2026.2667912","url":null,"abstract":"Introduction: Prion diseases comprise a heterogeneous group of rare and fatal neurodegenerative disorders characterized by self-propagating misfolding of the cellular prion protein. Although no therapy has yet proven capable of halting disease progression, several promising approaches are beginning to shift the field from repeated disappointment toward cautious but genuine translational optimism.Areas covered: This review examines emerging therapeutic approaches targeting key nodes of prion biology, including prion protein-targeting strategies and interventions directed at cellular pathways involved in disease pathogenesis. The authors further discuss the potential and challenges associated with polypharmacology, such as drug combinations and multi-target-directed ligands, which aim to address the biological complexity of prion disease.Expert opinion: The persistent limitations of single-target therapies for human prion disease emphasize the need to better align therapeutic strategies with disease stage, biological heterogeneity, and network-level pathogenesis. Achieving meaningful therapeutic impact will require an integrated strategy that brings together earlier intervention, improved patient stratification, and rational use of combination and multi-target approaches, supported by advances in biomarkers and experimental modeling.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"575-592"},"PeriodicalIF":7.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766667","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}

引用次数: 0

In vitro prediction of the immunogenicity of therapeutic proteins: state of the art and current challenges and perspectives. 治疗性蛋白免疫原性的体外预测：现状和当前的挑战和观点。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-06-01 Epub Date: 2026-05-04 DOI: 10.1080/17460441.2026.2665791

Olivier Fardel, Emna Mahfoudhi, Laurence Launay, Amélie Moreau, Claire Denizot, David Malnoë, Yannick Parmentier

{"title":"In vitro prediction of the immunogenicity of therapeutic proteins: state of the art and current challenges and perspectives.","authors":"Olivier Fardel, Emna Mahfoudhi, Laurence Launay, Amélie Moreau, Claire Denizot, David Malnoë, Yannick Parmentier","doi":"10.1080/17460441.2026.2665791","DOIUrl":"10.1080/17460441.2026.2665791","url":null,"abstract":"Introduction: Immunogenicity of therapeutic proteins is a major concern because it may compromise their clinical use and efficacy. Preclinical prediction of anti-drug antibody development using in vitro assays is therefore a challenge for candidate biologics.Areas covered: This review, based on a thorough literature search of the PubMed database up to December 2025, provides an overview of in vitro assays predicting biologic immunogenicity, including antigen internalization assay, dendritic cell activation assay, peptide-MHC II affinity measurement, MHC‑associated peptide proteomics (MAPPs) assay, and T cell activation/proliferation assays. The main features and applications of these assays are summarized, with special emphasis on their advantages and limitations.Expert opinion: Although in vitro immunogenicity assays are proposed to discriminate between low- and high-immunogenic biologics, they face numerous challenges. These include selecting the most appropriate test(s), lack of standardization in methods and technical parameters, defining positivity thresholds, high costs, the need for specialized equipment and trained personnel, the complexity and labor-intensive nature of assays, and the difficulty of translating in vitro results into clinical immunogenicity outcomes. Additional assay validation studies are undoubtedly required to better define the implementation and robustness of in vitro immunogenicity prediction for biologics, which could be advantageously combined with in silico approaches.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"655-673"},"PeriodicalIF":7.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766687","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}

引用次数: 0

Artificial intelligence in antimicrobial drug discovery: predictive and generative strategies. 抗菌药物发现中的人工智能：预测和生成策略。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-06-01 Epub Date: 2026-05-19 DOI: 10.1080/17460441.2026.2674968

Ximeng Duan, Na Liu, Lin Liu, Wei Geng, Dongmei Tan, Lin Liu, Hongxiang Lou, Xiuyun Li

{"title":"Artificial intelligence in antimicrobial drug discovery: predictive and generative strategies.","authors":"Ximeng Duan, Na Liu, Lin Liu, Wei Geng, Dongmei Tan, Lin Liu, Hongxiang Lou, Xiuyun Li","doi":"10.1080/17460441.2026.2674968","DOIUrl":"10.1080/17460441.2026.2674968","url":null,"abstract":"Introduction: The slow pipeline of antimicrobial drug development stands in stark contrast to the continued expansion of microbial infections, which pose a persistent and major threat to global public health. Traditional discovery strategies, including natural product extraction, structural modification and high-throughput screening, are limited by low efficiency, high costs and slow innovation. Artificial intelligence (AI), particularly machine learning, deep learning, and natural language processing, is now reshaping drug discovery, bringing unprecedented speed and precision to the development of novel antimicrobial drugs.Areas covered: This review summarizes recent advances and challenges in AI-driven strategies for discovering antimicrobial drugs against bacterial, fungal, and viral infections, covering major drug classes including small molecules, peptides, phages, and protein drugs. The article was based on literature retrieved through a structured, iterative search of major scientific databases (PubMed, Web of Science, Scopus), with a focus on studies published between 2020 and 2025.Expert opinion: The integration of AI-driven predictive and generative strategies will be the defining cornerstone of the next decade's 'autonomous discovery' paradigm for antimicrobial drug development, despite current enduring challenges including data bias, lack of standardized benchmarking frameworks, and clinical translational gaps.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"675-697"},"PeriodicalIF":7.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971992","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}

引用次数: 0