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

Perspectives on current approaches to virtual screening in drug discovery. 透视当前药物发现中的虚拟筛选方法。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-08-12 DOI: 10.1080/17460441.2024.2390511

Ingo Muegge, Jörg Bentzien, Yunhui Ge

{"title":"Perspectives on current approaches to virtual screening in drug discovery.","authors":"Ingo Muegge, Jörg Bentzien, Yunhui Ge","doi":"10.1080/17460441.2024.2390511","DOIUrl":"10.1080/17460441.2024.2390511","url":null,"abstract":"Introduction: For the past two decades, virtual screening (VS) has been an efficient hit finding approach for drug discovery. Today, billions of commercially accessible compounds are routinely screened, and many successful examples of VS have been reported. VS methods continue to evolve, including machine learning and physics-based methods.Areas covered: The authors examine recent examples of VS in drug discovery and discuss prospective hit finding results from the critical assessment of computational hit-finding experiments (CACHE) challenge. The authors also highlight the cost considerations and open-source options for conducting VS and examine chemical space coverage and library selections for VS.Expert opinion: The advancement of sophisticated VS approaches, including the use of machine learning techniques and increased computer resources as well as the ease of access to synthetically available chemical spaces, and commercial and open-source VS platforms allow for interrogating ultra-large libraries (ULL) of billions of molecules. An impressive number of prospective ULL VS campaigns have generated potent and structurally novel hits across many target classes. Nonetheless, many successful contemporary VS approaches still use considerably smaller focused libraries. This apparent dichotomy illustrates that VS is best conducted in a fit-for-purpose way choosing an appropriate chemical space. Better methods need to be developed to tackle more challenging targets.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1173-1183"},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916442","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

How to address the complexity of multi-targeted drug discovery for Alzheimer's disease? 如何应对阿尔茨海默病多靶点药物研发的复杂性？

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-07-29 DOI: 10.1080/17460441.2024.2385576

Juan F González, José M Sánchez-Montero

引用次数: 0

Approaches for the discovery of cinnamic acid derivatives with anticancer potential. 发现具有抗癌潜力的肉桂酸衍生物的方法。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-08-06 DOI: 10.1080/17460441.2024.2387122

Ioannis Fotopoulos, Dimitra Hadjipavlou-Litina

{"title":"Approaches for the discovery of cinnamic acid derivatives with anticancer potential.","authors":"Ioannis Fotopoulos, Dimitra Hadjipavlou-Litina","doi":"10.1080/17460441.2024.2387122","DOIUrl":"10.1080/17460441.2024.2387122","url":null,"abstract":"Introduction: Cinnamic acid is a privileged scaffold for the design of biologically active compounds with putative anticancer potential, following different synthetic methodologies and procedures. Since there is a need for the production of potent anticancer, cinnamate moiety can significantly contribute in the design of new and more active anticancer agents.Areas covered: In this review, the authors provide a review on the synthetic approaches for the discovery of cinnamic acid derivatives with anticancer potential. Results from molecular simulations, hybridization, and chemical derivatization along with biological experiments in vitro and structural activity relationships are given, described, and discussed by the authors. Information for the mechanism of action is taken from original literature sources.Expert opinion: The authors suggest that (i) numerous areas of biology-pharmacology need to be considered: selectivity, in vivo studies, toxicity and drug-likeness, the mechanism of action in animals and humans, development of more efficient assays for various cancer types; (ii) hybridization techniques outbalance in the discovery and production of compounds with higher activity and greater selectivity; (iii) repositioning offers new anticancer cinnamic agents.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1281-1291"},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893219","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

Molecular dynamics simulations for the structure-based drug design: targeting small-GTPases proteins. 用于基于结构的药物设计的分子动力学模拟：以小型 GTP 酶蛋白为目标。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-08-06 DOI: 10.1080/17460441.2024.2387856

Angela Parise, Sofia Cresca, Alessandra Magistrato

{"title":"Molecular dynamics simulations for the structure-based drug design: targeting small-GTPases proteins.","authors":"Angela Parise, Sofia Cresca, Alessandra Magistrato","doi":"10.1080/17460441.2024.2387856","DOIUrl":"10.1080/17460441.2024.2387856","url":null,"abstract":"Introduction: Molecular Dynamics (MD) simulations can support mechanism-based drug design. Indeed, MD simulations by capturing biomolecule motions at finite temperatures can reveal hidden binding sites, accurately predict drug-binding poses, and estimate the thermodynamics and kinetics, crucial information for drug discovery campaigns. Small-Guanosine Triphosphate Phosphohydrolases (GTPases) regulate a cascade of signaling events, that affect most cellular processes. Their deregulation is linked to several diseases, making them appealing drug targets. The broad roles of small-GTPases in cellular processes and the recent approval of a covalent KRas inhibitor as an anticancer agent renewed the interest in targeting small-GTPase with small molecules.Area covered: This review emphasizes the role of MD simulations in elucidating small-GTPase mechanisms, assessing the impact of cancer-related variants, and discovering novel inhibitors.Expert opinion: The application of MD simulations to small-GTPases exemplifies the role of MD simulations in the structure-based drug design process for challenging biomolecular targets. Furthermore, AI and machine learning-enhanced MD simulations, coupled with the upcoming power of quantum computing, are promising instruments to target elusive small-GTPases mutations and splice variants. This powerful synergy will aid in developing innovative therapeutic strategies associated to small-GTPases deregulation, which could potentially be used for personalized therapies and in a tissue-agnostic manner to treat tumors with mutations in small-GTPases.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1259-1279"},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893220","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 discovery and development of gefapixant as a novel antitussive therapy. 发现并开发了新型止咳疗法吉非匹克爽。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-08-13 DOI: 10.1080/17460441.2024.2391902

Maria Gabriella Matera, Paola Rogliani, Clive P Page, Luigino Calzetta, Mario Cazzola

{"title":"The discovery and development of gefapixant as a novel antitussive therapy.","authors":"Maria Gabriella Matera, Paola Rogliani, Clive P Page, Luigino Calzetta, Mario Cazzola","doi":"10.1080/17460441.2024.2391902","DOIUrl":"10.1080/17460441.2024.2391902","url":null,"abstract":"Introduction: Gefapixant, a P2X 3 receptor antagonist, shows considerable potential in managing refractory or unexplained chronic cough. Clinical trials have consistently demonstrated its efficacy in significantly reducing cough frequency and alleviating associated symptoms. However, its adverse effect profile, particularly taste disturbances such as dysgeusia and hypogeusia, the incidence of which is dose-dependent, poses a significant challenge to patient compliance and overall treatment satisfaction.Areas covered: The authors review the mechanism of action of gefapixant, the dose-dependent nature of its adverse effects and the findings from various clinical trials, including Phase 1, Phase 2, and Phase 3 studies. The authors also cover its regulatory status, post-marketing data, and its main competitors.Expert opinion: Gefapixant represents a significant advancement in treating chronic cough. However, balancing efficacy and tolerability is crucial. Lower effective doses and potential combination therapies may mitigate taste disturbances. Patient education and close monitoring during treatment are also important for optimal outcomes. Further research is needed to refine dosing strategies to minimize side effects while maintaining therapeutic efficacy. This research and personalized treatment approaches are key to optimizing gefapixant therapy, ensuring improved management of chronic cough while reducing adverse effects. However, pharmaceutical trials and proposals must be adapted to align with each regulatory body's specific requirements and concerns.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1159-1172"},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975504","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

Promising animal models for amyotrophic lateral sclerosis drug discovery: a comprehensive update. 用于肌萎缩性脊髓侧索硬化症药物研发的前景看好的动物模型：全面更新。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-08-08 DOI: 10.1080/17460441.2024.2387791

Léa Lescouzères, Shunmoogum A Patten

{"title":"Promising animal models for amyotrophic lateral sclerosis drug discovery: a comprehensive update.","authors":"Léa Lescouzères, Shunmoogum A Patten","doi":"10.1080/17460441.2024.2387791","DOIUrl":"10.1080/17460441.2024.2387791","url":null,"abstract":"Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Several animal models have been generated to understand ALS pathogenesis. They have provided valuable insight into disease mechanisms and the development of therapeutic strategies.Areas covered: In this review, the authors provide a concise overview of simple genetic model organisms, including C. elegans, Drosophila, zebrafish, and mouse genetic models that have been generated to study ALS. They emphasize the benefits of each model and their application in translational research for discovering new chemicals, gene therapy approaches, and antibody-based strategies for treating ALS.Expert opinion: Significant progress is being made in identifying new therapeutic targets for ALS. This progress is being enabled by promising animal models of the disease using increasingly effective genetic and pharmacological strategies. There are still challenges to be overcome in order to achieve improved success rates for translating drugs from animal models to clinics for treating ALS. Several promising future directions include the establishment of novel preclinical protocol standards, as well as the combination of animal models with human induced pluripotent stem cells (iPSCs).","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1213-1233"},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901476","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

Correction. 更正。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-08-19 DOI: 10.1080/17460441.2024.2392351

引用次数: 0

Targeting polo-like kinase 1: advancements and future directions in anti-cancer drug discovery. 靶向多聚样激酶 1：抗癌药物研发的进展与未来方向。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-07-29 DOI: 10.1080/17460441.2024.2385603

Monika Raab, Sven Becker, Mourad Sanhaji

引用次数: 0

New horizons for obsessive-compulsive disorder drug discovery: is targeting glutamate receptors the answer? 强迫症药物研发的新视野：谷氨酸受体是答案吗？

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-08-06 DOI: 10.1080/17460441.2024.2387127

Giacomo Grassi, Edoardo Scillitani, Chiara Cecchelli

{"title":"New horizons for obsessive-compulsive disorder drug discovery: is targeting glutamate receptors the answer?","authors":"Giacomo Grassi, Edoardo Scillitani, Chiara Cecchelli","doi":"10.1080/17460441.2024.2387127","DOIUrl":"10.1080/17460441.2024.2387127","url":null,"abstract":"Introduction: Over the past decade, glutamate has emerged as a prominent focus in the field of obsessive-compulsive disorder (OCD) pathophysiology. A convergence of evidence from genetic, preclinical, and clinical studies points to glutamatergic dysfunction as a key feature of this condition. In light of these findings, there has been a growing interest in exploring the potential of glutamatergic agents in the treatment of OCD.Areas covered: This paper reviews the literature on glutamate transmission in OCD. In addition, the authors examine the results of clinical trials investigating the efficacy of glutamatergic agents in the treatment of OCD patients.Expert opinion: Along with the recognition of neuroinflammation in the brain in OCD, the evidence of glutamate dysfunction represents one of the most promising recent discoveries for understanding the mechanisms involved in OCD. The importance of this discovery lies primarily in its pharmacological implications and has led to intense research activity in the field of glutamatergic agents. While this research has not yet had a substantial clinical impact, targeting glutamate receptors remains a promising horizon for the successful treatment of OCD patients.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1235-1245"},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893221","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

Opportunities and challenges with G-quadruplexes as promising targets for drug design. 将 G 型四联体作为有前途的药物设计目标的机遇与挑战。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-09-18 DOI: 10.1080/17460441.2024.2404230

Victoria Sanchez-Martin

{"title":"Opportunities and challenges with G-quadruplexes as promising targets for drug design.","authors":"Victoria Sanchez-Martin","doi":"10.1080/17460441.2024.2404230","DOIUrl":"https://doi.org/10.1080/17460441.2024.2404230","url":null,"abstract":"INTRODUCTIONG-quadruplexes (G4s) are secondary structures formed in guanine-rich regions of nucleic acids (both DNA and RNA). G4s are significantly enriched at regulatory genomic regions and are associated with important biological processes ranging from telomere homeostasis and genome instability to transcription and translation. Importantly, G4s are related to health and diseases such as cancer, neurological diseases, as well as infections with viruses and microbial pathogens. Increasing evidence suggests the potential of G4s for designing new diagnostic and therapeutic strategies although in vivo studies are still at early stages.AREAS COVEREDThis review provides an updated summary of the literature describing the impact of G4s in human diseases and different approaches based on G4 targeting in therapy.EXPERT OPINIONWithin the G4 field, most of the studies have been performed in vitro and in a descriptive manner. Therefore, detailed mechanistic understanding of G4s in the biological context remains to be deciphered. In clinics, the use of G4s as therapeutic targets has been hindered due to the low selectivity profile and poor drug-like properties of G4 ligands. Future research on G4s may overcome current methodological and interventional limitations and shed light on these unique structural elements in the pathogenesis and treatment of diseases.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":"103 1","pages":"1-15"},"PeriodicalIF":6.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263068","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