Expert Opinion on Drug Discovery最新文献_第4页

The root cause: why do so many drugs fail to translate from bench to bedside? 根本原因是：为什么这么多的药物不能从实验室转化为临床？

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-08-01 Epub Date: 2026-06-18 DOI: 10.1080/17460441.2026.2665217

Andre Levchenko, Mark Corrigan, Bruce Wexler

引用次数: 0

Targeting ferroptosis in lung cancer: emerging strategies and drug discovery opportunities. 靶向肺癌铁下垂：新策略和药物发现机会。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-08-01 Epub Date: 2026-07-31 DOI: 10.1080/17460441.2026.2708187

Qianyi Chen, Hao Liu, Cien Sun, Ziming Wang, William C Cho, Jianfei Shen

{"title":"Targeting ferroptosis in lung cancer: emerging strategies and drug discovery opportunities.","authors":"Qianyi Chen, Hao Liu, Cien Sun, Ziming Wang, William C Cho, Jianfei Shen","doi":"10.1080/17460441.2026.2708187","DOIUrl":"10.1080/17460441.2026.2708187","url":null,"abstract":"Introduction: Lung cancer remains the leading cause of cancer-related mortality worldwide, with lung adenocarcinoma (LUAD) being its most prevalent histological subtype, which is plagued by severe drug resistance and dismal long-term survival. Current treatment approaches are often limited by drug resistance and metastasis. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, represents a promising novel therapeutic target to address these unmet clinical needs.Areas covered: The authors of this narrative review synthesize the preclinical and translational evidence for ferroptosis-targeted lung cancer therapy and provide the reader with their expert perspectives on future development. Literature was retrieved from PubMed, Web of Science, Embase and China National Knowledge Infrastructure (CNKI) covering publications published between January 2018 and March 2026.Expert opinion: While ferroptosis induction effectively reverses therapeutic resistance in preclinical lung cancer models, its clinical translation is impeded by off-target toxicity, inconsistent subtype responses and the lack of validated predictive biomarkers. Ferroptosis agents will likely act as combinatorial adjuvants rather than monotherapies in the foreseeable future. Advancing subtype-selective compounds and multi-omics stratification signatures are essential to realize its clinical potential.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"865-884"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629944","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

Balancing optimism versus potential risks of AI-driven drug discovery. 平衡乐观与人工智能驱动的药物发现的潜在风险。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-08-01 Epub Date: 2026-06-24 DOI: 10.1080/17460441.2026.2691836

Jonathan D Hirst

引用次数: 0

Why next-generation mechanistic models will transform drug discovery: integrating efficacy and safety. 为什么下一代机制模型将改变药物发现：整合疗效和安全性。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-08-01 Epub Date: 2026-07-08 DOI: 10.1080/17460441.2026.2699304

Gustavo Santos Sandes Felizardo, Vinícius Alexandre Fiaia Costa, Eder Soares de Almeida Santos, Luiz Carlos da Cunha, Bruno Junior Neves

{"title":"Why next-generation mechanistic models will transform drug discovery: integrating efficacy and safety.","authors":"Gustavo Santos Sandes Felizardo, Vinícius Alexandre Fiaia Costa, Eder Soares de Almeida Santos, Luiz Carlos da Cunha, Bruno Junior Neves","doi":"10.1080/17460441.2026.2699304","DOIUrl":"10.1080/17460441.2026.2699304","url":null,"abstract":"Introduction: Drug discovery remains constrained by high attrition rates and the fragmented evaluation of exposure, efficacy, and safety. Mechanistic models offer a biologically grounded framework for connecting these determinants across multiple levels of biological organization. This may help improve translational decision-making by supporting earlier and more integrated assessment of candidate progression.Areas covered: This narrative review examines the conceptual basis and current role of next-generation mechanistic models in drug discovery, with emphasis on physiologically based pharmacokinetic models, virtual cell-based assays, quantitative systems pharmacology, artificial intelligence (AI)-augmented mechanistic models, and emerging virtual-cell frameworks. It highlights how these approaches may connect efficacy and safety across biological scales, support in vitro-to-in vivo extrapolation, incorporate in silico predictions, and improve candidate prioritization. The literature was surveyed through PubMed searches conducted up to 25 May 2026.Expert opinion: Next-generation mechanistic models are unlikely to transform drug discovery simply by increasing biological detail or computational sophistication. Progress in this direction will depend on standardized data streams, robust validation, explicit model calibration, reproducibility, tighter integration between models, and careful alignment between model design and context of use. Under these conditions, mechanistic frameworks may become important components of a more predictive and less attrition-prone drug discovery pipeline.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"885-900"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381896","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

From mitochondrial signal to discovery decision: a reserve-demand framework for translational risk assessment. 从线粒体信号到发现决策：翻译风险评估的储备-需求框架。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-08-01 Epub Date: 2026-07-03 DOI: 10.1080/17460441.2026.2697796

George W Rogers, Yvonne Will

{"title":"From mitochondrial signal to discovery decision: a reserve-demand framework for translational risk assessment.","authors":"George W Rogers, Yvonne Will","doi":"10.1080/17460441.2026.2697796","DOIUrl":"10.1080/17460441.2026.2697796","url":null,"abstract":"Introduction: Mitochondrial safety assessment is used in drug discovery, supported by bioenergetic profiling, mechanistic assays, human-relevant cellular systems, and multidimensional data. These advances have improved detection of mitochondrial perturbation but have not solved the harder problem: how such signals should be interpreted and translated into discovery decisions.Areas covered: This perspective proposes a qualitative decision-centered framework for interpreting mitochondrial findings. This framework is anchored in reserve-demand biology, which explains why mitochondrial perturbations become consequential when drug-induced reductions in bioenergetic capacity intersect with tissue-specific demand, exposure, duration, and stress context. Furthermore, the authors describe a qualitative Translational Risk Profile organized around mechanistic severity, exposure relevance, temporal progression, and translational concordance. This profile is paired with a Decision Taxonomy: Stop, Optimize, Monitor, or Acceptable Risk. Examples illustrate how mitochondrial evidence patterns can support different discovery actions.Expert opinion: The major limitation in mitochondrial safety assessment is no longer signal detection, but decision-oriented interpretation. Future progress will depend on integrating mechanism, exposure, duration, biomarkers, human-relevant models and quantitative or computational evidence into explicit decision frameworks. Mitochondrial findings should not be treated as binary hazards. They should be interpreted as context-dependent evidence that can guide chemistry, candidate selection, monitoring strategy, and translational risk management.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"839-853"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351453","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

Preclinical discovery and clinical development of glofitamab in relapsed/ refractory large B-cell lymphomas. 格非他单抗治疗复发/难治性大b细胞淋巴瘤的临床前发现和临床进展。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-08-01 Epub Date: 2026-06-07 DOI: 10.1080/17460441.2026.2678871

Philipp Berning, Gilles Salles

{"title":"Preclinical discovery and clinical development of glofitamab in relapsed/ refractory large B-cell lymphomas.","authors":"Philipp Berning, Gilles Salles","doi":"10.1080/17460441.2026.2678871","DOIUrl":"10.1080/17460441.2026.2678871","url":null,"abstract":"Introduction: Relapsed/refractory (R/R) large B-cell lymphoma (LBCL) remains a clinical challenge, particularly for patients with primary refractory or relapsed disease and ineligible for cellular therapies. T-cell engagers in the form of CD20xCD3 bispecific antibodies (BsAb) offer an effective 'off-the-shelf' therapy option that redirects endogenous T cells against malignant B cells.Areas covered: This review summarizes the preclinical and translational development of glofitamab, a full-length 2:1 BsAb, focusing on R/R LBCL. The authors discuss the molecular design rationale, mechanism of action, and preclinical efficacy that enabled clinical translation. They review clinical development milestones across monotherapy and combination regimens in heavily pretreated R/R LBCL, activity after CAR T-cell therapy, and data supporting movement into earlier lines and strategies for older/unfit patients. This article is based on clinical trial reports and major trial registrations in B-cell lymphomas obtained via PubMed and ClinicalTrials.gov, covering literature published up to January 2026.Expert opinion: Glofitamab provides clinically meaningful, time-limited treatment achieving disease control in patients who are ineligible for autologous HCT and/or CAR T-cell therapy and for those relapsing after CAR T-cell therapy. Future research will be needed on biomarker-guided sequencing, optimized toxicity/infection mitigation, and combination strategies that improve durable response rates.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"827-837"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197918","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

Toward a nuanced framework for the medical development of ibogaine and its analogues and derivatives: implications for psychopharmacology. 伊博加因及其类似物和衍生物的医学发展的微妙框架：对精神药理学的影响。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-08-01 Epub Date: 2026-07-06 DOI: 10.1080/17460441.2026.2693144

Christopher D Verrico, Lynnette A Averill, Cameron J Moore, Amy L McGuire, Thomas R Kosten, Ramiro Salas

{"title":"Toward a nuanced framework for the medical development of ibogaine and its analogues and derivatives: implications for psychopharmacology.","authors":"Christopher D Verrico, Lynnette A Averill, Cameron J Moore, Amy L McGuire, Thomas R Kosten, Ramiro Salas","doi":"10.1080/17460441.2026.2693144","DOIUrl":"10.1080/17460441.2026.2693144","url":null,"abstract":"Introduction: Ibogaine is a naturally occurring indole alkaloid with suggested therapeutic potential across substance use disorders, trauma-related conditions, mood disorders, and suicidality. However, its clinical translation has been hindered by safety concerns, regulatory barriers, and uncertainty regarding its complex pharmacology. Recent interest has surged in developing ibogaine analogs and derivatives that retain therapeutic efficacy while minimizing safety risks. Ibogaine pharmacology is complex with many affected targets, which complicates these efforts.Areas covered: Herein, the authors propose a conceptual framework that distinguishes between two primary strategies: (1) development of ibogaine-like compounds that preserve broad, polypharmacological effects while mitigating key safety liabilities, and (2) creation of more selective, purpose-built 'bespoke' analogs designed to optimally target specific neurobiological pathways and clinical indications-such as opioid use disorder (OUD), traumatic brain injury, or post-traumatic stress disorder (PTSD). Furthermore, the authors critically evaluate the current evidence supporting each approach, and discuss the translational trade-offs related to safety, efficacy, comorbidity, and scalability. The authors also highlight the importance of individual variability, including pharmacogenetics in treatment response.Expert opinion: It is important, and particularly within policy-driven research initiatives, that this evolving field must resist oversimplified narratives that frame derivatives as uniformly superior or interchangeable. Greater conceptual clarity and mechanistic humility are also essential as ibogaine-based therapies move toward regulated medical use within Westernized healthcare models.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"855-864"},"PeriodicalIF":7.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381953","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

Epigenetic reactivation in Friedreich's ataxia from benzamides to gene‑targeted chimeras. 从苯酰胺到基因靶向嵌合体friedrreich共济失调的表观遗传再激活。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-07-01 Epub Date: 2026-06-16 DOI: 10.1080/17460441.2026.2689723

Faizan U Ansari, Teerapat Rojsajjakul, Jiayi Liu, Sathiji K Nageshwaran, Ian A Blair

{"title":"Epigenetic reactivation in Friedreich's ataxia from benzamides to gene‑targeted chimeras.","authors":"Faizan U Ansari, Teerapat Rojsajjakul, Jiayi Liu, Sathiji K Nageshwaran, Ian A Blair","doi":"10.1080/17460441.2026.2689723","DOIUrl":"10.1080/17460441.2026.2689723","url":null,"abstract":"Introduction: Friedreich's ataxia (FRDA) is a prototypical repeat expansion disorder in which large intronic guanine‑adenine‑adenine (GAA) tracts at the frataxin (FXN) gene locus induce heterochromatin formation, impaired transcriptional elongation, and reduced FXN expression, driving progressive neurodegeneration and cardiomyopathy. Epigenetic therapies that restore endogenous FXN transcription have therefore emerged as a coherent disease‑modifying strategy focused on reversing repeat‑associated gene silencing at its root.Areas covered: This review summarizes the evolution of FXN protein‑reactivating approaches from first‑generation systemic epigenetic therapies, including class I‑selective benzamide histone deacetylase inhibitors and high‑dose nicotinamide, to emerging locus‑targeted platforms such as anti‑gene oligonucleotides and gene‑targeted chimera small molecules. The authors also examine splice‑modulating strategies aimed at increasing the extra‑mitochondrial FXN‑E isoform, discuss delivery and safety challenges across modalities, and highlight biomarker frameworks integrating isoform‑resolved FXN protein measurements and chromatin readouts. PubMed/MEDLINE, Embase, Web of Science, Google Scholar, and Cochrane Library for trial reports were searched from January 1996 to June 2026.Expert opinion: Early clinical programs established that FXN protein expression and chromatin marks can be pharmacologically modulated in humans, but also exposed the limitations of non‑selective chromatin modulation for chronic pediatric‑onset neurodegeneration. In our view, the most promising path forward lies in repeat‑ and locus‑directed FXN reactivation, complemented by splicing‑directed modulation of FXN‑E, with rigorous attention to CNS and cardiac exposure, off‑target risk, and mechanistically anchored biomarkers.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"779-791"},"PeriodicalIF":7.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249985","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

Advances in 3D cell culture models for alzheimer's disease drug discovery. 用于阿尔茨海默病药物发现的三维细胞培养模型的进展。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-07-01 Epub Date: 2026-06-27 DOI: 10.1080/17460441.2026.2691833

Karla Valdivia-Aviña, Sarah Eliuth Ochoa-Hugo, Mercedes Azucena Hernández-Sapiéns, Alejandro Arturo Canales-Aguirre

{"title":"Advances in 3D cell culture models for alzheimer's disease drug discovery.","authors":"Karla Valdivia-Aviña, Sarah Eliuth Ochoa-Hugo, Mercedes Azucena Hernández-Sapiéns, Alejandro Arturo Canales-Aguirre","doi":"10.1080/17460441.2026.2691833","DOIUrl":"10.1080/17460441.2026.2691833","url":null,"abstract":"Introduction: Alzheimer's Disease (AD) affects more than 57 million people, yet drug development faces high failure rates due to the limited translational validity of conventional models. This review analyzes how 3D (three-dimensional) systems provide a technical validation platform that more accurately replicates the human brain microenvironment.Areas covered: This review analyzes the evolution of 3D culture systems, including spheroids, organoids, hydrogels, and microfluidics. A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and ScienceDirect, covering publications from January 2014 to March 2026. The analysis synthesizes evidence on the capacity of these models to reproduce beta-amyloid (β-amyloid) aggregation and tau hyperphosphorylation, while exploring the integration of artificial intelligence to optimize compound screening.Expert opinion: 3D models serve as high-fidelity biological filters that complement current preclinical methodologies, improving early identification of toxicities and therapeutic efficacy. Their strategic integration and technical standardization are essential steps to refine predictive accuracy and optimize the transition to clinical trials.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"761-777"},"PeriodicalIF":7.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338333","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

Building tomorrow's medicines: how robotic synthesis is actualizing AI's drug discovery promise. 构建明天的药物：机器人合成如何实现人工智能的药物发现承诺。

IF 7.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2026-07-01 Epub Date: 2026-06-07 DOI: 10.1080/17460441.2026.2684572

Dinesh Kumar

引用次数: 0