Expert Opinion on Drug Discovery最新文献_第8页

Challenges with drug efficacy prediction of in vitro models of biofilms infecting cystic fibrosis airway. 囊性纤维化气道生物膜感染体外模型药效预测面临的挑战。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-06-01 Epub Date: 2024-05-07 DOI: 10.1080/17460441.2024.2350567

Ana Margarida Sousa, Maria Olívia Pereira

引用次数: 0

Innovative peptide architectures: advancements in foldamers and stapled peptides for drug discovery. 创新肽结构：折叠肽和钉肽在药物发现方面的进展。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-06-01 Epub Date: 2024-05-16 DOI: 10.1080/17460441.2024.2350568

Zhou Dongrui, Maho Miyamoto, Hidetomo Yokoo, Yosuke Demizu

{"title":"Innovative peptide architectures: advancements in foldamers and stapled peptides for drug discovery.","authors":"Zhou Dongrui, Maho Miyamoto, Hidetomo Yokoo, Yosuke Demizu","doi":"10.1080/17460441.2024.2350568","DOIUrl":"10.1080/17460441.2024.2350568","url":null,"abstract":"Introduction: Peptide foldamers play a critical role in pharmaceutical research and biomedical applications. This review highlights recent (post-2020) advancements in novel foldamers, synthetic techniques, and their applications in pharmaceutical research.Areas covered: The authors summarize the structures and applications of peptide foldamers such as α, β, γ-peptides, hydrocarbon-stapled peptides, urea-type foldamers, sulfonic-γ-amino acid foldamers, aromatic foldamers, and peptoids, which tackle the challenges of traditional peptide drugs. Regarding antimicrobial use, foldamers have shown progress in their potential against drug-resistant bacteria. In drug development, peptide foldamers have been used as drug delivery systems (DDS) and protein-protein interaction (PPI) inhibitors.Expert opinion: These structures exhibit resistance to enzymatic degradation, are promising for therapeutic delivery, and disrupt crucial PPIs associated with diseases such as cancer with specificity, versatility, and stability, which are useful therapeutic properties. However, the complexity and cost of their synthesis, along with the necessity for thorough safety and efficacy assessments, necessitate extensive research and cross-sector collaboration. Advances in synthesis methods, computational modeling, and targeted delivery systems are essential for fully realizing the therapeutic potential of foldamers and integrating them into mainstream medical treatments.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"699-723"},"PeriodicalIF":6.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957000","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

Using DNA-encoded libraries of fragments for hit discovery of challenging therapeutic targets. 利用 DNA 编码的片段库发现具有挑战性的治疗靶点。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-06-01 Epub Date: 2024-05-16 DOI: 10.1080/17460441.2024.2354287

Guixian Zhao, Mengping Zhu, Yangfeng Li, Gong Zhang, Yizhou Li

{"title":"Using DNA-encoded libraries of fragments for hit discovery of challenging therapeutic targets.","authors":"Guixian Zhao, Mengping Zhu, Yangfeng Li, Gong Zhang, Yizhou Li","doi":"10.1080/17460441.2024.2354287","DOIUrl":"10.1080/17460441.2024.2354287","url":null,"abstract":"Introduction: The effectiveness of Fragment-based drug design (FBDD) for targeting challenging therapeutic targets has been hindered by two factors: the small library size and the complexity of the fragment-to-hit optimization process. The DNA-encoded library (DEL) technology offers a compelling and robust high-throughput selection approach to potentially address these limitations.Area covered: In this review, the authors propose the viewpoint that the DEL technology matches perfectly with the concept of FBDD to facilitate hit discovery. They begin by analyzing the technical limitations of FBDD from a medicinal chemistry perspective and explain why DEL may offer potential solutions to these limitations. Subsequently, they elaborate in detail on how the integration of DEL with FBDD works. In addition, they present case studies involving both de novo hit discovery and full ligand discovery, especially for challenging therapeutic targets harboring broad drug-target interfaces.Expert opinion: The future of DEL-based fragment discovery may be promoted by both technical advances and application scopes. From the technical aspect, expanding the chemical diversity of DEL will be essential to achieve success in fragment-based drug discovery. From the application scope side, DEL-based fragment discovery holds promise for tackling a series of challenging targets.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"725-740"},"PeriodicalIF":6.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957008","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

Another string to your bow: machine learning prediction of the pharmacokinetic properties of small molecules. 您的另一项任务：通过机器学习预测小分子药物的药代动力学特性。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-06-01 Epub Date: 2024-05-10 DOI: 10.1080/17460441.2024.2348157

Davide Bassani, Neil John Parrott, Nenad Manevski, Jitao David Zhang

{"title":"Another string to your bow: machine learning prediction of the pharmacokinetic properties of small molecules.","authors":"Davide Bassani, Neil John Parrott, Nenad Manevski, Jitao David Zhang","doi":"10.1080/17460441.2024.2348157","DOIUrl":"10.1080/17460441.2024.2348157","url":null,"abstract":"Introduction: Prediction of pharmacokinetic (PK) properties is crucial for drug discovery and development. Machine-learning (ML) models, which use statistical pattern recognition to learn correlations between input features (such as chemical structures) and target variables (such as PK parameters), are being increasingly used for this purpose. To embed ML models for PK prediction into workflows and to guide future development, a solid understanding of their applicability, advantages, limitations, and synergies with other approaches is necessary.Areas covered: This narrative review discusses the design and application of ML models to predict PK parameters of small molecules, especially in light of established approaches including in vitro-in vivo extrapolation (IVIVE) and physiologically based pharmacokinetic (PBPK) models. The authors illustrate scenarios in which the three approaches are used and emphasize how they enhance and complement each other. In particular, they highlight achievements, the state of the art and potentials of applying machine learning for PK prediction through a comphrehensive literature review.Expert opinion: ML models, when carefully crafted, regularly updated, and appropriately used, empower users to prioritize molecules with favorable PK properties. Informed practitioners can leverage these models to improve the efficiency of drug discovery and development process.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"683-698"},"PeriodicalIF":6.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897857","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

Lessons learnt from machine learning in early stages of drug discovery. 从药物发现早期阶段的机器学习中汲取的经验教训。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-06-01 Epub Date: 2024-05-10 DOI: 10.1080/17460441.2024.2354279

Claudio N Cavasotto, Juan I Di Filippo, Valeria Scardino

引用次数: 0

New drug discovery strategies for the treatment of benznidazole-resistance in Trypanosoma cruzi, the causative agent of Chagas disease. 治疗南美锥虫病病原体克氏锥虫对苯并咪唑耐药性的新药研发战略。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-06-01 Epub Date: 2024-05-07 DOI: 10.1080/17460441.2024.2349155

Silvane Maria Fonseca Murta, Pedro Augusto Lemos Santana, Thibault Joseph William Jacques Dit Lapierre, André Berndt Penteado, Marissa El Hajje, Thabata Corazza Navarro Vinha, Daniel Barbosa Liarte, Mariana Laureano de Souza, Gustavo Henrique Goulart Trossini, Celso de Oliveira Rezende Júnior, Renata Barbosa de Oliveira, Rafaela Salgado Ferreira

{"title":"New drug discovery strategies for the treatment of benznidazole-resistance in Trypanosoma cruzi, the causative agent of Chagas disease.","authors":"Silvane Maria Fonseca Murta, Pedro Augusto Lemos Santana, Thibault Joseph William Jacques Dit Lapierre, André Berndt Penteado, Marissa El Hajje, Thabata Corazza Navarro Vinha, Daniel Barbosa Liarte, Mariana Laureano de Souza, Gustavo Henrique Goulart Trossini, Celso de Oliveira Rezende Júnior, Renata Barbosa de Oliveira, Rafaela Salgado Ferreira","doi":"10.1080/17460441.2024.2349155","DOIUrl":"10.1080/17460441.2024.2349155","url":null,"abstract":"Introduction: Benznidazole, the drug of choice for treating Chagas Disease (CD), has significant limitations, such as poor cure efficacy, mainly in the chronic phase of CD, association with side effects, and parasite resistance. Understanding parasite resistance to benznidazole is crucial for developing new drugs to treat CD.Areas covered: Here, the authors review the current understanding of the molecular basis of benznidazole resistance. Furthermore, they discuss the state-of-the-art methods and critical outcomes employed to evaluate the efficacy of potential drugs against T. cruzi, aiming to select better compounds likely to succeed in the clinic. Finally, the authors describe the different strategies employed to overcome resistance to benznidazole and find effective new treatments for CD.Expert opinion: Resistance to benznidazole is a complex phenomenon that occurs naturally among T. cruzi strains. The combination of compounds that inhibit different metabolic pathways of the parasite is an important strategy for developing a new chemotherapeutic protocol.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"741-753"},"PeriodicalIF":6.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876171","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

Recent advances in computational and experimental protein-ligand affinity determination techniques. 计算和实验蛋白质配体亲和力测定技术的最新进展。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-06-01 Epub Date: 2024-05-07 DOI: 10.1080/17460441.2024.2349169

Visvaldas Kairys, Lina Baranauskiene, Migle Kazlauskiene, Asta Zubrienė, Vytautas Petrauskas, Daumantas Matulis, Egidijus Kazlauskas

{"title":"Recent advances in computational and experimental protein-ligand affinity determination techniques.","authors":"Visvaldas Kairys, Lina Baranauskiene, Migle Kazlauskiene, Asta Zubrienė, Vytautas Petrauskas, Daumantas Matulis, Egidijus Kazlauskas","doi":"10.1080/17460441.2024.2349169","DOIUrl":"10.1080/17460441.2024.2349169","url":null,"abstract":"Introduction: Modern drug discovery revolves around designing ligands that target the chosen biomolecule, typically proteins. For this, the evaluation of affinities of putative ligands is crucial. This has given rise to a multitude of dedicated computational and experimental methods that are constantly being developed and improved.Areas covered: In this review, the authors reassess both the industry mainstays and the newest trends among the methods for protein - small-molecule affinity determination. They discuss both computational affinity predictions and experimental techniques, describing their basic principles, main limitations, and advantages. Together, this serves as initial guide to the currently most popular and cutting-edge ligand-binding assays employed in rational drug design.Expert opinion: The affinity determination methods continue to develop toward miniaturization, high-throughput, and in-cell application. Moreover, the availability of data analysis tools has been constantly increasing. Nevertheless, cross-verification of data using at least two different techniques and careful result interpretation remain of utmost importance.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"649-670"},"PeriodicalIF":6.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876172","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

Hits and misses with animal models of narcolepsy and the implications for drug discovery. 嗜睡症动物模型的成功与失败以及对药物研发的影响。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-06-01 Epub Date: 2024-05-15 DOI: 10.1080/17460441.2024.2354293

Ramakrishna Nirogi, Pradeep Jayarajan, Vijay Benade, Renny Abraham, Vinod Kumar Goyal

{"title":"Hits and misses with animal models of narcolepsy and the implications for drug discovery.","authors":"Ramakrishna Nirogi, Pradeep Jayarajan, Vijay Benade, Renny Abraham, Vinod Kumar Goyal","doi":"10.1080/17460441.2024.2354293","DOIUrl":"10.1080/17460441.2024.2354293","url":null,"abstract":"Introduction: Narcolepsy is a chronic and rare neurological disorder characterized by disordered sleep. Based on animal models and further research in humans, the dysfunctional orexin system was identified as a contributing factor to the pathophysiology of narcolepsy. Animal models played a larger role in the discovery of some of the pharmacological agents with established benefit/risk profiles.Areas covered: In this review, the authors examine the phenotypes observed in animal models of narcolepsy and the characteristics of clinically used pharmacological agents in these animal models. Additionally, the authors compare the effects of clinically used pharmacological agents on the phenotypes in animal models with those observed in narcolepsy patients.Expert opinion: Research in canine and mouse models have linked narcolepsy to the O×R2mutation and orexin deficiency, leading to new diagnostic criteria and a drug development focus. Advancements in pharmacological therapies have significantly improved narcolepsy management, with insights from both clinical experience and from animal models having led to new treatments such as low sodium oxybate and solriamfetol. However, challenges persist in addressing symptoms beyond excessive daytime sleepiness and cataplexy, highlighting the need for further research, including the development of diurnal animal models to enhance understanding and treatment options for narcolepsy.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"755-768"},"PeriodicalIF":6.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920935","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

What is the plausibility that all drugs will be designed by computers by the end of the decade? 到本十年末，所有药物都由计算机设计的可能性有多大？

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-05-01 Epub Date: 2024-03-19 DOI: 10.1080/17460441.2024.2331734

José L Medina-Franco, Edgar López-López

引用次数: 0

Using automated patch clamp electrophysiology platforms in ion channel drug discovery: an industry perspective. 在离子通道药物发现中使用自动膜片钳电生理学平台：行业视角。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-05-01 Epub Date: 2024-03-13 DOI: 10.1080/17460441.2024.2329104

Marc Rogers, Alison Obergrussberger, Artem Kondratskyi, Niels Fertig

{"title":"Using automated patch clamp electrophysiology platforms in ion channel drug discovery: an industry perspective.","authors":"Marc Rogers, Alison Obergrussberger, Artem Kondratskyi, Niels Fertig","doi":"10.1080/17460441.2024.2329104","DOIUrl":"10.1080/17460441.2024.2329104","url":null,"abstract":"Introduction: Automated patch clamp (APC) is now well established as a mature technology for ion channel drug discovery in academia, biotech and pharma companies, and in contract research organizations (CRO), for a variety of applications including channelopathy research, compound screening, target validation and cardiac safety testing.Areas covered: Ion channels are an important class of drugged and approved drug targets. The authors present a review of the current state of ion channel drug discovery along with new and exciting developments in ion channel research involving APC. This includes topics such as native and iPSC-derived cells in ion channel drug discovery, channelopathy research, organellar and biologics in ion channel drug discovery.Expert opinion: It is our belief that APC will continue to play a critical role in ion channel drug discovery, not only in 'classical' hit screening, target validation and cardiac safety testing, but extending these applications to include high throughput organellar recordings and optogenetics. In this way, with advancements in APC capabilities and applications, together with high resolution cryo-EM structures, ion channel drug discovery will be re-invigorated, leading to a growing list of ion channel ligands in clinical development.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"523-535"},"PeriodicalIF":6.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119220","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