Expert Opinion on Drug Discovery最新文献_第3页

Cortical bone loss in osteoporosis: the rabbit as a platform for drug discovery and testing. 骨质疏松症的皮质骨丢失：兔作为药物发现和测试的平台。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-09-01 Epub Date: 2025-07-25 DOI: 10.1080/17460441.2025.2536045

Xuan Wei, Kim D Harrison, Lindsay L Loundagin, David M L Cooper

{"title":"Cortical bone loss in osteoporosis: the rabbit as a platform for drug discovery and testing.","authors":"Xuan Wei, Kim D Harrison, Lindsay L Loundagin, David M L Cooper","doi":"10.1080/17460441.2025.2536045","DOIUrl":"10.1080/17460441.2025.2536045","url":null,"abstract":"Introduction: Osteoporosis (OP) affects bone quality and quantity of millions of people worldwide. Osteoporotic fractures significantly decrease the quality of life of patients and are associated with increased mortality in the following years. Thus, there is continued clinical interest in treatments that preserve bone and mitigate fracture risk. As a routine method, several preclinical animal models exist to test current and potential OP treatments. However, most studies focus on trabecular bone, while cortical bone is under-studied, despite its significant role in bone strength and fragility.Areas covered: The authors review the available on the use of the rabbit model to investigate the pathophysiology and treatments (antiresorptive and osteoanabolic) of OP, emphasizing cortical bone outcomes. Google Scholar was utilized to find the most up-to-date literature on the subject.Expert opinion: The rabbit model of OP is suitable choice for investigation treatments in cortical bone, owing to its human-like cortical remodeling process, which is fundamental to the development of OP. Opportunities exist to utilize novel imaging and histological methods with the rabbit model to examine the mechanisms underpinning the pathophysiology of OP, and to investigate existing and new targets for drug discovery at a microscopic level within the cortical bone compartment.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1169-1192"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706929","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

Novel insights into structure-activity relationships of kynurenine 3-monooxygenase inhibitors (KMOis) with emphasis on chemical space, activity landscape exploration. 犬尿氨酸3-单加氧酶抑制剂（KMOis）结构-活性关系的新见解，重点是化学空间，活性景观探索。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-09-01 Epub Date: 2025-07-16 DOI: 10.1080/17460441.2025.2532688

Chaitali Mallick, Sagnik Banerjee, Sk Abdul Amin

{"title":"Novel insights into structure-activity relationships of kynurenine 3-monooxygenase inhibitors (KMOis) with emphasis on chemical space, activity landscape exploration.","authors":"Chaitali Mallick, Sagnik Banerjee, Sk Abdul Amin","doi":"10.1080/17460441.2025.2532688","DOIUrl":"10.1080/17460441.2025.2532688","url":null,"abstract":"Introduction: Kynurenine 3-monooxygenase (KMO) is a pivotal target in the kynurenine pathway (KP). KMO inhibitors (KMOis) decrease neurotoxic metabolites like 3-hydroxykynurenine and quinolinic acid while increasing neuroprotective kynurenic acid levels. It offers a promising therapeutic approach for treating neurodegenerative diseases, psychiatric disorders, acute pancreatitis, and immune-mediated conditions.Areas covered: The authors provide an overview of the biology and function of KMO and highlight the key evidence for KMOi design. The authors also provide a summary of the structure - activity relationships (SARs) of several series of KMOis based on a comprehensive search of literature utilizing PubMed, Google Scholar, and Scopus, covering the period between 2015 and 2025. This works also provides explicit coverage to the chemical space of human KMOis (hKMOis), thereby providing a novel framework for the rational design of next-generation therapeutics targeting this enzyme.Expert opinion: The KP, particularly KMO, has emerged as a compelling target for drug discovery. The Structure-Similarity Activity Trailing (SimilACTrail) map of hKMOis has provided novel insights for mapping the molecular landscape of hKMOis. A high scaffold-hopping rate (40.24%) underscores the potential for chemical innovation, while the identification of activity cliffs (0.58%) provides critical data for refining SARs. These findings offer a promising avenue for therapeutic development, with opportunities for the optimization of chemical scaffolds.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1209-1221"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642189","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 potential of academic drug discovery: successes and challenges. 学术药物发现的潜力：成功与挑战。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-09-01 Epub Date: 2025-07-02 DOI: 10.1080/17460441.2025.2528125

Matthew Stremlau, Barbara S Slusher

引用次数: 0

Bisquinoline as a promising scaffold in anti-infective drug discovery: the current state of the art and future prospects. 双喹啉作为抗感染药物发现中有前景的支架：现状及未来展望。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-09-01 Epub Date: 2025-07-29 DOI: 10.1080/17460441.2025.2539203

Swagatika Dash, Suvarna G Kini, Amit Sharma

{"title":"Bisquinoline as a promising scaffold in anti-infective drug discovery: the current state of the art and future prospects.","authors":"Swagatika Dash, Suvarna G Kini, Amit Sharma","doi":"10.1080/17460441.2025.2539203","DOIUrl":"10.1080/17460441.2025.2539203","url":null,"abstract":"Introduction: Bisquinoline is a privileged pharmacophore in medicinal chemistry due to its diverse biological activities, particularly against infectious diseases such as malaria, tuberculosis, leishmania, fungi, bacteria, protozoa, schistosomiasis, and HIV. The success of piperaquine, a bisquinoline-derived antimalarial, has underscored its therapeutic potential, driving interest in its role as a small-molecule probe for targeting critical disease pathways. As drug resistance increases and the need for effective treatments rises, bisquinoline's broad pharmacological profile presents promising drug discovery opportunities.Areas covered: This review explores research on bisquinoline derivatives as anti-infective agents, focusing on synthetic approaches, detailed structure-activity relationships, and therapeutic applications. It includes detailed insights into piperaquine, the only approved bisquinoline drug, based on literature from 2000 to 2025 sourced from PubMed, Scopus, and Web of Science concerning 'bisquinoline scaffold' keywords.Expert opinion: In the last two decades, significant progress has been made in developing bisquinoline derivatives with various pharmacological effects. These advancements have expanded our understanding of the scaffold's pharmacological diversity and its potential for creating more effective drugs with fewer side effects. This continued progression will aid the development of the next-generation of bisquinoline-based therapeutics.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1141-1168"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741693","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

Understanding the key challenges in tuberculosis drug discovery: what does the future hold? 了解结核病药物发现的主要挑战：未来会怎样？

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-09-01 Epub Date: 2025-07-12 DOI: 10.1080/17460441.2025.2531229

Rima Zein-Eddine, Masoud Ramuz, Guislaine Refrégier, Johannes F Lutzeyer, Alexey Aleksandrov, Hannu Myllykallio

{"title":"Understanding the key challenges in tuberculosis drug discovery: what does the future hold?","authors":"Rima Zein-Eddine, Masoud Ramuz, Guislaine Refrégier, Johannes F Lutzeyer, Alexey Aleksandrov, Hannu Myllykallio","doi":"10.1080/17460441.2025.2531229","DOIUrl":"10.1080/17460441.2025.2531229","url":null,"abstract":"Introduction: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health concern. It spreads through airborne droplets and has a high mortality rate, particularly without treatment. Drug resistance is rising, with treatments against multidrug-resistant TB (MDR-TB) showing poor treatment success rates. The thick, lipid-rich wall of Mtb and its slow growth reduce antibiotic effectiveness, requiring long treatment courses of 4-6 months. Current therapies often fail against drug-resistant strains, highlighting the urgent need for new, short-course treatment, affordable, and combination-friendly drugs.Areas covered: Within this perspective, the authors review and comment on the following topics regarding Mtb resistance emergence and treatment strategies: i) Existing treatment ii) Resistance evolution in Mtb; iii) Key challenges in drug discovery targeting Mtb; iv) emerging strategies and recent advances in Mtb drug discovery, and v) Next-generation approaches. Literature was identified through a search of PubMed, google scholar, and web of science, from January 2010 to March 2025.Expert opinion: AI is accelerating the discovery of bioavailable and safe preclinical drug candidates for TB, though data limitations and biological complexity remain challenging. Future progress requires multi-modal models, open-access datasets, and interdisciplinary collaboration.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1115-1130"},"PeriodicalIF":4.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616856","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 upadacitinib for the treatment of Crohn's disease. 用于治疗克罗恩病的upadacitinib的临床前发现和开发。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-08-01 Epub Date: 2025-06-27 DOI: 10.1080/17460441.2025.2522890

Sophie Vieujean, Silvio Danese, Laurent Peyrin-Biroulet

{"title":"The preclinical discovery and development of upadacitinib for the treatment of Crohn's disease.","authors":"Sophie Vieujean, Silvio Danese, Laurent Peyrin-Biroulet","doi":"10.1080/17460441.2025.2522890","DOIUrl":"10.1080/17460441.2025.2522890","url":null,"abstract":"Introduction: The JAK-STAT pathway plays a pivotal role in immune regulation and is implicated in the pathogenesis of Crohn's disease (CD). Upadacitinib is a JAK inhibitor with greater selectivity for JAK1 over JAK2 and JAK3, and is emerging as a promising alternative to biologic therapies in CD.Areas covered: A literature search of MEDLINE and EMBASE up to February 2025 was conducted using defined keywords to identify preclinical, clinical, and real-world studies on upadacitinib in CD. In early trials, upadacitinib demonstrated efficacy in reducing proinflammatory cytokines, improving intestinal barrier integrity, and achieving high intracellular drug concentrations in target tissues. The phase II CELEST trial demonstrated that upadacitinib induced both endoscopic and clinical responses in patients with moderate-to-severe CD. Subsequent phase III studies (U-EXCEED, U-EXCEL, U-ENDURE) confirmed rapid clinical remission, sustained efficacy, and a manageable safety profile, leading to regulatory approval. The efficacy and safety of this molecule in CD have been confirmed by real-world studies.Expert opinion: The currently available data suggests that upadacitinib is an effective oral therapy for CD, offering an alternative to biologics with predictable pharmacokinetics, rapid symptom relief, and sustained long-term benefits. Future research will refine its role in treatment algorithms, biomarker-driven personalization, and combination therapies.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"951-971"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505301","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 models of insomnia: advances, limitations, and future directions for drug discovery. 失眠的临床前模型：进展、局限性和药物发现的未来方向。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-08-01 Epub Date: 2025-07-02 DOI: 10.1080/17460441.2025.2528135

Oscar Arias-Carrión

{"title":"Preclinical models of insomnia: advances, limitations, and future directions for drug discovery.","authors":"Oscar Arias-Carrión","doi":"10.1080/17460441.2025.2528135","DOIUrl":"10.1080/17460441.2025.2528135","url":null,"abstract":"Introduction: Insomnia is a highly prevalent and clinically burdensome disorder that profoundly affects cognition, emotional regulation, cardiometabolic health, and neurodegenerative progression. Despite advances in understanding its neurobiology, current animal models fail to capture the chronic, heterogeneous, and comorbid nature of human insomnia, impeding progress in translational drug discovery.Areas covered: This narrative review critically appraises genetic, environmental, pharmacological, and circuit-level models of insomnia, focusing on their translational relevance to drug discovery and is based on literature searches using PubMed and Scopus (2000-2025) where key systematic reviews were identified. The author also discusses how oversimplified paradigms and limited modeling of comorbidity constrain clinical applicability and highlight emerging tools - optogenetics, chemogenetics, CRISPR, wearable EEG, and AI - that enable high-resolution mapping of sleep - wake mechanisms.Expert opinion: A paradigm shift toward integrated, multidimensional models is urgently needed to reflect the complexity of chronic insomnia better. Embedding these models into translational pipelines - through precision genetics, circuit manipulation, and AI-enhanced analytics - will accelerate mechanism-based drug discovery and support the development of durable, personalized treatments for this disabling and multifactorial disorder.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1061-1074"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527108","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

Designing drugs against leishmaniasis: is targeting the sterol biosynthesis pathway the answer? 设计抗利什曼病药物：靶向甾醇生物合成途径是答案吗？

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-08-01 Epub Date: 2025-07-12 DOI: 10.1080/17460441.2025.2530589

Gonzalo Visbal, Maribel Navarro

{"title":"Designing drugs against leishmaniasis: is targeting the sterol biosynthesis pathway the answer?","authors":"Gonzalo Visbal, Maribel Navarro","doi":"10.1080/17460441.2025.2530589","DOIUrl":"10.1080/17460441.2025.2530589","url":null,"abstract":"Introduction: Leishmaniasis is a devastating and complex parasitic disease caused by different species of protozoan members of the genus Leishmania. Unfortunately, available drugs are far from ideal and no vaccines are available. Under these circumstances, new effective antileishmanial drugs with reduced host toxicity and improved dosing protocols are urgently needed. The sterol biosynthesis pathway (SBP) is a promising focus for combating Leishmania infections. Thus, various strategies have been documented, such as drug repurposing, combined therapy, rational drug design, and the use of synergistic effects to develop the metallodrugs that can act on essential parasite targets.Areas covered: This article reviews the critical enzymes participating in the ergostane-based sterol biosynthesis pathway (SBP) of Leishmania species, as well as recent progress in rational drug design, repurposing drugs, combined therapies, and the development of metallodrugs for use as antileishmanial agents. This review is based on literature searchers using SciFinder, Lens.org, Google Scholar, Web of Science, Pub Med, and DrugBank.Expert opinion: The limited focus on human leishmaniasis has resulted in a shortfall in effective treatments for this parasitic disease. The post-squalene segment of the sterol biosynthetic pathway is a promising target for treating Leishmania infections, particularly effective drugs or metallodrugs that inhibit the CYP51 or 24-SMT enzymes.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1031-1044"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616854","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 impact of CD3 affinity-attenuation on T cell engaging bispecific antibodies: is it really that simple? CD3亲和力衰减对T细胞参与双特异性抗体的影响：真的那么简单吗？

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-08-01 Epub Date: 2025-06-23 DOI: 10.1080/17460441.2025.2522088

Omar Abdelmotaleb, Anneliese Schneider, Christian Gassner, Stephan Märsch, Christian Klein

{"title":"The impact of CD3 affinity-attenuation on T cell engaging bispecific antibodies: is it really that simple?","authors":"Omar Abdelmotaleb, Anneliese Schneider, Christian Gassner, Stephan Märsch, Christian Klein","doi":"10.1080/17460441.2025.2522088","DOIUrl":"10.1080/17460441.2025.2522088","url":null,"abstract":"Introduction: The first generation of approved T cell engagers (TCEs) showing promising efficacy in hematological and solid tumors relies on high binding affinity to CD3. Treatment of tumors with TCEs has been clinically associated with toxicities related to cytokine release syndrome (CRS). In addition to clinical strategies to mitigate CRS, antibody engineering efforts have been undertaken to generate TCEs with optimized therapeutic index. Strategies pursued in this context include affinity attenuation of CD3 binding arm, to achieve potent tumor cell killing with minimal cytokine secretion.Areas covered: A literature search was conducted to identify peer-reviewed articles related to CD3 affinity and T cell engagers. Here, we provide an overview of the current state and recent developments in CD3 affinity-attenuation, both preclinically and clinically, with a focus on the challenges of developing TCEs with attenuated affinity to CD3 as well as identifying possible areas of improvement.Expert opinion: CD3 affinity reduction can effectively lower cytokine levels preclinically; however, it is crucial to consider all factors influencing the mode of action of TCEs. Prioritizing the use of the most translatable preclinical models is essential to identify the right candidates for further development.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"943-949"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474415","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 the application of NMR to the study of GPCRs and ligand-GPCR interactions. 核磁共振在gpcr及其配体- gpcr相互作用研究中的应用进展。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-08-01 Epub Date: 2025-06-10 DOI: 10.1080/17460441.2025.2515045

Olga A Alimowska, Afnan Khan, R Scott Prosser

{"title":"Advances in the application of NMR to the study of GPCRs and ligand-GPCR interactions.","authors":"Olga A Alimowska, Afnan Khan, R Scott Prosser","doi":"10.1080/17460441.2025.2515045","DOIUrl":"10.1080/17460441.2025.2515045","url":null,"abstract":"Introduction: GPCRs are targeted by nearly one-third of FDA-approved drugs and are therefore of great interest in drug discovery pursuits. Nuclear magnetic resonance (NMR) builds upon our understanding of the structural biology of GPCRs by helping to identify dynamic facets of ligand engagement, activation, and G protein coupling, often through the identification of an ensemble.Areas covered: The basic facets of NMR spectroscopy and relaxation experiments (e.g. CPMG, WaterLOGSY, STD) are described as they pertain to the study of structure activity relationships (SAR), ligand-fragment interaction dynamics, and fragment-based drug discovery. This article is based on literature searches that have utilized ISI Web of Knowledge, MEDLINE, and Google Scholar.Expert opinion: The structural biology of GPCRs and their associated complexes are rapidly advancing, particularly via cryoEM techniques which provide high-resolution structures and additional insights into minor states represented into the ensemble. Nevertheless, there is still an important niche for NMR methods to capture in terms of the delineation of detailed and physiologically representative ensembles of functional states and their associated dynamics.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"973-989"},"PeriodicalIF":4.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247220","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