Expert Opinion on Drug Discovery最新文献

The latest progress in assay development in leishmaniasis drug discovery: a review of the available papers on PubMed from the past year.

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-01-06 DOI: 10.1080/17460441.2025.2450787

Gabriela P Dos Santos, Adriano C Coelho, Juliana Q Reimao

{"title":"The latest progress in assay development in leishmaniasis drug discovery: a review of the available papers on PubMed from the past year.","authors":"Gabriela P Dos Santos, Adriano C Coelho, Juliana Q Reimao","doi":"10.1080/17460441.2025.2450787","DOIUrl":"https://doi.org/10.1080/17460441.2025.2450787","url":null,"abstract":"Introduction: Leishmaniasis is a significant neglected tropical disease with limited treatment options that urgently requires ongoing efforts in drug discovery. Recent advances have focused on the development of new assays and methods to identify effective therapeutic candidates.Areas covered: This review explores recent trends and methodologies in leishmaniasis drug discovery, with a particular focus on in silico and in vitro studies, as well as in vivo validation, using animal models. A detailed analysis of recent studies was provided, discussing the methodologies employed, such as manual and automated parasite quantification, and the use of fluorescence and luminescence-based techniques. Additionally, global research trends were analyzed, highlighting the leading countries in scientific output and the collaborative efforts driving advancements in this field.Expert opinion: The field of leishmaniasis drug discovery has rapidly progressed in the last years, but the lack of standardized methodologies and limited in vivo validation remain significant hurdles. To advance promising treatments to clinical trials, cross-validation of preclinical findings and interdisciplinary collaboration are essential. Increased funding and global partnerships are also crucial to accelerate the discovery and development of alternative and effective therapies.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931066","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 anticancer drug discovery efforts targeting glycosylation: the emergence of fluorinated monosaccharides analogs.

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-01-06 DOI: 10.1080/17460441.2024.2444375

Ana F Costa, Andreia Teixeira, Celso A Reis, Catarina Gomes

{"title":"Novel anticancer drug discovery efforts targeting glycosylation: the emergence of fluorinated monosaccharides analogs.","authors":"Ana F Costa, Andreia Teixeira, Celso A Reis, Catarina Gomes","doi":"10.1080/17460441.2024.2444375","DOIUrl":"10.1080/17460441.2024.2444375","url":null,"abstract":"Introduction: Glycosylation is an essential enzymatic process of building glycan structures that occur mainly within the cell and gives rise to a diversity of cell surface and secreted glycoconjugates. These glycoconjugates play vital roles, for instance in cellcell adhesion, interaction and communication, activation of cell surface receptors, inflammatory response and immune recognition. This controlled and wellcoordinated enzymatic process is altered in cancer, leading to the biosynthesis of cancerassociated glycans, which impact glycandependent biological roles.Areas covered: In this review, the authors discuss the importance of targeting cancerassociated glycans through potent glycan biosynthesis inhibitors. It focuses on the use of analogs, providing an overview of findings involving these in cancer. The highly explored fluorinated monosaccharide analogs targeting aberrant glycosylation are described, aiming to inspire advances in the field.Expert opinion: Altered glycosylation, such as increased sialylation and fucosylation, is a feature in cancer and has been shown to play key roles in several malignant properties of cancer cells. Strategies aiming at remodeling cancer cells´ glycome are emerging and present a huge potential for cancer therapy. Fluorinated monosaccharides have been gathering promising preclinical results as novel cancer drugs. Nevertheless, cancer specific targeting strategies must be considered to avoid significant sideeffects.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-11"},"PeriodicalIF":6.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920892","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

Approach advancements for engineering novel peptide analogs of existing lantibiotics: where are we today?

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-01-01 Epub Date: 2024-12-21 DOI: 10.1080/17460441.2024.2441351

Thushinari Joseph, Leif Smith

{"title":"Approach advancements for engineering novel peptide analogs of existing lantibiotics: where are we today?","authors":"Thushinari Joseph, Leif Smith","doi":"10.1080/17460441.2024.2441351","DOIUrl":"10.1080/17460441.2024.2441351","url":null,"abstract":"Introduction: The emergence of antibiotic resistance among the clinically important bacterial pathogens has increased healthcare costs and reduced patient safety and quality of life. Lantibiotics is a large class of ribosomally synthesized, and posttranslationally modified peptides have been the primary focus of numerous research aimed at discovering compounds for treating bacterial infections.Areas covered: The article explains the most up to date hierarchy of methods followed in the field for high throughput screening of lantibiotics/analogs with improved therapeutic properties. Herein, we explain how the structure and the biosynthesis of lantibiotics can be manipulated for the expansion of the horizon of lantibiotic potency. Furthermore, we discuss the lantibiotic analogs that have demonstrated the efficacy against bacterial pathogens of interest in animal models.Expert opinion: In this current age of rapidly advancing antimicrobial resistance, there is a dire need for the development of therapeutic agents that possess distinct mechanisms of action to existing modes of treatment. Recent advances in the understanding of many of the lantibiotic biosynthesis systems and the discovery of new analogs with superior properties to the native compound may have paved the way for the development of a much-needed novel potent class of antibiotic.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"17-30"},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817733","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

A cautionary tale of paradox and false positives in cannabidiol research.

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI: 10.1080/17460441.2024.2441359

Peter S Cogan

{"title":"A cautionary tale of paradox and false positives in cannabidiol research.","authors":"Peter S Cogan","doi":"10.1080/17460441.2024.2441359","DOIUrl":"10.1080/17460441.2024.2441359","url":null,"abstract":"Introduction: Decades of research on cannabidiol (CBD) have identified thousands of purported cellular effects, and many of these have been proposed to correlate with a vast therapeutic potential. Yet despite the large volume of findings fueling broad optimism in this regard, few have translated into any demonstrable clinical benefit or even notable side effects. Therein resides the great paradox of CBD: a drug that appears to affect almost everything in vitro does not clearly do much of anything in a clinical setting.Areas covered: Comparative critical evaluation of literature searched in PubMed and Google Scholar discovers multiple instances of inconsistent and contradictory findings regarding the pharmacology and clinical effects of CBD, as well as several uncelebrated reports that suggest potential explanations for these observations. Many of those effects attributed to the ostensible pharmacologic activity of cannabidiol are almost certainly the product of false-positive experimental results and artifactual findings that are unlikely to be realized under physiologic conditions.Expert opinion: Concerns regarding the physiological relevance and translational potential of in vitro findings across the field of cannabinoid research are both far-reaching and demanding of attention in the form of appropriate experimental controls that remain almost universally absent.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"5-15"},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812531","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 design and development of chemical modulators of the voltage-gated potassium channels K_V7.4 and K_V7.5.

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-01-01 Epub Date: 2024-12-09 DOI: 10.1080/17460441.2024.2438226

Jana Lemke, Maik Gollasch, Dmitry Tsvetkov, Lukas Schulig

{"title":"Advances in the design and development of chemical modulators of the voltage-gated potassium channels KV7.4 and KV7.5.","authors":"Jana Lemke, Maik Gollasch, Dmitry Tsvetkov, Lukas Schulig","doi":"10.1080/17460441.2024.2438226","DOIUrl":"10.1080/17460441.2024.2438226","url":null,"abstract":"Introduction: Hypertension remains a major public health concern, with significant morbidity and mortality worldwide. Despite the availability of various antihypertensive medications, blood pressure control remains suboptimal in many individuals. During the last decades, KV7.4 and KV7.5, which were already known from the view of neuronal regulation, emerged as possible important players in the regulation of vascular tone and blood pressure.Areas covered: This review covers physiological functions and current advancements in the development of KV7.4 and KV7.5 channel modulators. The authors highlight the structural elements likely to be important for the future design of KV7 subtype-selective modulators, underscoring their potential as an innovative hypertension treatment.Expert opinion: Extensive research has been focused on targeting neuronal KV7.2 and KV7.3 channels, while KV7.4 and KV7.5 attracted less attention. Many of the developed compounds represent derivatives of flupirtine or retigabine, whereby subtype channel selectivity has only been demonstrated for a handful of individual compounds. Novel substances address additional sites within the binding pocket by incorporating new functional groups. A comprehensive and systematic evaluation of a compound set with significant subtype selectivity should be performed. The discovery of new highly active, less toxic, and selective compounds, therefore, remains the goal of further research in the coming years.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"47-62"},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767186","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

Evolution of antisense oligonucleotides: navigating nucleic acid chemistry and delivery challenges. 反义寡核苷酸的演变：驾驭核酸化学和递送挑战。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI: 10.1080/17460441.2024.2440095

Ruchi Ruchi, Govind Mukesh Raman, Vikas Kumar, Raman Bahal

{"title":"Evolution of antisense oligonucleotides: navigating nucleic acid chemistry and delivery challenges.","authors":"Ruchi Ruchi, Govind Mukesh Raman, Vikas Kumar, Raman Bahal","doi":"10.1080/17460441.2024.2440095","DOIUrl":"10.1080/17460441.2024.2440095","url":null,"abstract":"Introduction: Antisense oligonucleotide (ASO) was established as a viable therapeutic option for genetic disorders. ASOs can target RNAs implicated in various diseases, including upregulated mRNA and pre-mRNA undergoing abnormal alternative splicing events. Therapeutic applications of ASOs have been proven with the Food and Drug Administration approval of several drugs in recent years. Earlier enzymatic stability and delivery remains a big challenge for ASOs. Introducing new chemical modifications and new formulations resolving the issues related to the nuclease stability and delivery of the ASOs. Excitingly, ASOs-based bioconjugates that target the hepatocyte have gained much attraction. Efforts are ongoing to increase the therapeutic application of the ASOs to the extrahepatic tissue as well.Area covered: We have briefly discussed the mechanism of ASOs, the development of new chemistries, and delivery strategies for ASO-based drug discovery and development. The discussion focuses more on the already approved ASOs and those in the clinical development stage.Expert opinion: To expand the clinical application of ASOs, continuous effort is required to develop precise delivery strategies for targeting extrahepatic tissue to minimize the off-target effects.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"63-80"},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799877","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

Validation guidelines for drug-target prediction methods. 药物靶点预测方法的验证指南。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-01-01 Epub Date: 2024-11-21 DOI: 10.1080/17460441.2024.2430955

Ziaurrehman Tanoli, Aron Schulman, Tero Aittokallio

{"title":"Validation guidelines for drug-target prediction methods.","authors":"Ziaurrehman Tanoli, Aron Schulman, Tero Aittokallio","doi":"10.1080/17460441.2024.2430955","DOIUrl":"10.1080/17460441.2024.2430955","url":null,"abstract":"Introduction: Mapping the interactions between pharmaceutical compounds and their molecular targets is a fundamental aspect of drug discovery and repurposing. Drug-target interactions are important for elucidating mechanisms of action and optimizing drug efficacy and safety profiles. Several computational methods have been developed to systematically predict drug-target interactions. However, computational and experimental validation of the drug-target predictions greatly vary across the studies.Areas covered: Through a PubMed query, a corpus comprising 3,286 articles on drug-target interaction prediction published within the past decade was covered. Natural language processing was used for automated abstract classification to study the evolution of computational methods, validation strategies and performance assessment metrics in the 3,286 articles. Additionally, a manual analysis of 259 studies that performed experimental validation of computational predictions revealed prevalent experimental protocols.Expert opinion: Starting from 2014, there has been a noticeable increase in articles focusing on drug-target interaction prediction. Docking and regression stands out as the most commonly used techniques among computational methods, and cross-validation is frequently employed as the computational validation strategy. Testing the predictions using multiple, orthogonal validation strategies is recommended and should be reported for the specific target prediction applications. Experimental validation remains relatively rare and should be performed more routinely to evaluate biological relevance of predictions.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"31-45"},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681195","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

Development of environmentally biodegradable drugs: what are the key challenges?

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-01-01 Epub Date: 2024-12-24 DOI: 10.1080/17460441.2024.2442746

Michael G Bertram, Bob B M Wong, Klaus Kümmerer, Manuela Jörg

引用次数: 0

Integrated machine learning and physics-based methods assisted de novo design of Fatty Acyl-CoA synthase inhibitors. 基于机器学习和物理学的综合方法辅助从头设计脂肪酸酰-CoA 合酶抑制剂。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-01-01 Epub Date: 2024-11-25 DOI: 10.1080/17460441.2024.2432972

Atul Pawar, Hemchandra Deka, Monishka Battula, Hossam M Aljawdah, Preeti Chunarkar Patil, Rupesh Chikhale

{"title":"Integrated machine learning and physics-based methods assisted de novo design of Fatty Acyl-CoA synthase inhibitors.","authors":"Atul Pawar, Hemchandra Deka, Monishka Battula, Hossam M Aljawdah, Preeti Chunarkar Patil, Rupesh Chikhale","doi":"10.1080/17460441.2024.2432972","DOIUrl":"10.1080/17460441.2024.2432972","url":null,"abstract":"Background: Tuberculosis is an infectious disease that has become endemic worldwide. The causative bacteria Mycobacterium tuberculosis (Mtb) is targeted via several exciting drug targets. One newly discovered target is the Fatty Acyl-CoA synthase, which plays a significant role in activating the long-chain fatty acids.Research design & methods: This study aims to generate novel compounds using Machine Learning (ML) algorithms to inhibit this synthase. Experimentally derived bioactive compounds were chosen from ChEMBL and used as inputs for effective molecule generation by Reinvent4. The library of new molecules generated was subjected to a two-tiered molecular docking protocol, and the results were further studied to obtain a binding free energy check.Results: The ML-based de novo drug design (DNDD) approach successfully generated a diverse library of novel molecules targeting Fatty Acyl-CoA synthase. After rigorous molecular docking and binding free energy analysis, four new compounds were identified as potential lead candidates with promising inhibitory effects on Mtb lipid metabolism.Conclusions: The study demonstrated the effectiveness of a machine-learning approach in generating novel drug candidates against Mtb. The identified hit compounds show potential as inhibitors of Fatty Acyl-CoA synthase, offering a new avenue for developing treatments for tuberculosis, particularly in combating drug-resistant strains.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"123-135"},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715894","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 anticancer drug discovery strategies targeting hypoxia-inducible factors.

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI: 10.1080/17460441.2024.2442739

Muhamad Mustafa, Mahmoud Rashed, Jean-Yves Winum

{"title":"Novel anticancer drug discovery strategies targeting hypoxia-inducible factors.","authors":"Muhamad Mustafa, Mahmoud Rashed, Jean-Yves Winum","doi":"10.1080/17460441.2024.2442739","DOIUrl":"10.1080/17460441.2024.2442739","url":null,"abstract":"Introduction: Hypoxia is a key feature of solid tumors, associated with aggressive behaviors such as radiation and chemotherapy resistance, increased metastasis, and poor prognosis. Hypoxia-inducible factors (HIFs) are essential transcription factors that help tumor cells adapt to hypoxic environments by promoting the expression of pro-oncogenic genes. Reducing HIF activity presents a promising strategy for advancing cancer treatment.Area covered: In this paper, the authors present an overview of recent studies on the development of HIF-1/2 inhibitors as potential anticancer drugs. The article offers a comprehensive analysis of the structural characteristics of these inhibitors and explores their relationship with anticancer activity, focusing on research conducted over the past decade, from 2015 to 2024.Expert opinion: Because they play a big role in medicinal chemistry and the discovery of anticancer drugs, HIF inhibitors have always gotten a lot of attention and have been used to make a lot of important molecules with different biological effects, especially in the field of cancer research. Several techniques and chemical scaffolds have successfully targeted HIF-1α. However, additional research is required to sustain HIF-1α inhibition while maintaining anticancer activity. The FDA approval of Belzutifan provided researchers with an opportunity to conduct broader HIF-2 studies.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"103-121"},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817734","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