Expert Opinion on Drug Discovery最新文献_第7页

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

The progress and challenges in modeling colorectal cancer and the impact on novel drug discovery. 结直肠癌建模的进展和挑战以及对新药研发的影响。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-09-16 DOI: 10.1080/17460441.2024.2404238

Natália Teixeira, Ana Baião, Sofia Dias, Bruno Sarmento

{"title":"The progress and challenges in modeling colorectal cancer and the impact on novel drug discovery.","authors":"Natália Teixeira, Ana Baião, Sofia Dias, Bruno Sarmento","doi":"10.1080/17460441.2024.2404238","DOIUrl":"https://doi.org/10.1080/17460441.2024.2404238","url":null,"abstract":"Introduction: Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. This disease is complex and heterogeneous, influenced by a variety of genetic, epigenetic, and environmental factors that drive CRC initiation and progression. Despite advances in therapeutic strategies, the five-year survival rate for metastatic CRC is alarmingly low. Traditional two-dimensional (2D) cell culture systems have been the foundation of cancer research, but their inability to replicate the complex tumor microenvironment (TME) limits their effectiveness.Areas covered: This paper explores the evolution of CRC models, starting with the limitations of traditional 2D cell culture systems and the significant advancements offered by 3D models. Additionally, it highlights 3D bioprinting and on-chip CRC models, which have enhanced the ability to mimic in vivo conditions.Expert opinion: The transition to advanced 3D models represents a pivotal shift in CRC research, offering considerable improvements over the established 2D models. These models hold promise for the development of patient-specific models that better mimic in vivo conditions. However, the inherent complexity of CRC continues to pose challenges in developing models that can fully capture the disease's multifaceted nature. This complexity and high costs associated with these technologies, along with the need for standardized protocols, pose significant challenges to their widespread adoption.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-10"},"PeriodicalIF":6.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282781","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 are the translational challenges associated with Chagas disease drug discovery? 与南美锥虫病药物研发相关的转化挑战有哪些？

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-09-13 DOI: 10.1080/17460441.2024.2402409

Inmaculada Ramírez-Macías,Paola García-Huertas,Clotilde Marín

引用次数: 0

Advances in the approaches used to repurpose drugs for neuroblastoma. 神经母细胞瘤药物再利用方法的进展。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-09-11 DOI: 10.1080/17460441.2024.2402413

Marta Miera-Maluenda,María Pérez-Torres,Adriana Mañas,Alba Rubio-San-Simón,Maria Butjosa-Espín,Paula Ruiz-Duran,Jose A Seoane,Lucas Moreno,Miguel F Segura

{"title":"Advances in the approaches used to repurpose drugs for neuroblastoma.","authors":"Marta Miera-Maluenda,María Pérez-Torres,Adriana Mañas,Alba Rubio-San-Simón,Maria Butjosa-Espín,Paula Ruiz-Duran,Jose A Seoane,Lucas Moreno,Miguel F Segura","doi":"10.1080/17460441.2024.2402413","DOIUrl":"https://doi.org/10.1080/17460441.2024.2402413","url":null,"abstract":"INTRODUCTIONNeuroblastoma (NB) remains a challenging pediatric malignancy with limited treatment options, particularly for high-risk cases. Drug repurposing offers a convenient and cost-effective strategy for treating rare diseases like NB. Using existing drugs with known safety profiles accelerates the availability of new treatments, reduces development costs, and mitigates risks, offering hope for improved patient outcomes in challenging conditions.AREAS COVEREDThis review provides an overview of the advances in approaches used to repurpose drugs for NB therapy. The authors discuss strategies employed in drug repurposing, including computational and experimental methods, and rational drug design, highlighting key examples of repurposed drugs with promising clinical results. Additionally, the authors examine the challenges and opportunities associated with drug repurposing in NB and discuss future directions and potential areas for further research.EXPERT OPINIONThe fact that only one new drug has been approved in the last 30 years for the treatment of neuroblastoma plus a significant proportion of high-risk NB patients that remain uncurable, evidences the need for new fast and cost-effective alternatives. Drug repurposing may accelerate the treatment development process while reducing expenses and risks. This approach can swiftly bring effective NB therapies to market, enhancing survival rates and patient quality of life.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":"121 1","pages":"1-11"},"PeriodicalIF":6.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221469","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 broad-spectrum coronavirus antiviral drug discovery. 广谱冠状病毒抗病毒药物研发的经验教训。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-09-01 Epub Date: 2024-07-30 DOI: 10.1080/17460441.2024.2385598

Andrew A Bolinger, Jun Li, Xuping Xie, Hongmin Li, Jia Zhou

{"title":"Lessons learnt from broad-spectrum coronavirus antiviral drug discovery.","authors":"Andrew A Bolinger, Jun Li, Xuping Xie, Hongmin Li, Jia Zhou","doi":"10.1080/17460441.2024.2385598","DOIUrl":"10.1080/17460441.2024.2385598","url":null,"abstract":"Introduction: Highly pathogenic coronaviruses (CoVs), such as severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and the most recent SARS-CoV-2 responsible for the COVID-19 pandemic, pose significant threats to human populations over the past two decades. These CoVs have caused a broad spectrum of clinical manifestations ranging from asymptomatic to severe distress syndromes (ARDS), resulting in high morbidity and mortality.Areas covered: The accelerated advancements in antiviral drug discovery, spurred by the COVID-19 pandemic, have shed new light on the imperative to develop treatments effective against a broad spectrum of CoVs. This perspective discusses strategies and lessons learnt in targeting viral non-structural proteins, structural proteins, drug repurposing, and combinational approaches for the development of antivirals against CoVs.Expert opinion: Drawing lessons from the pandemic, it becomes evident that the absence of efficient broad-spectrum antiviral drugs increases the vulnerability of public health systems to the potential onslaught by highly pathogenic CoVs. The rapid and sustained spread of novel CoVs can have devastating consequences without effective and specifically targeted treatments. Prioritizing the effective development of broad-spectrum antivirals is imperative for bolstering the resilience of public health systems and mitigating the potential impact of future highly pathogenic CoVs.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1023-1041"},"PeriodicalIF":6.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent developments in the application of immobilized artificial membrane (IAM) chromatography to drug discovery. 固定人工膜（IAM）色谱法在药物发现中应用的最新进展。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-09-01 Epub Date: 2024-07-03 DOI: 10.1080/17460441.2024.2374409

Fotios Tsopelas, Theodosia Vallianatou, Anna Tsantili-Kakoulidou

{"title":"Recent developments in the application of immobilized artificial membrane (IAM) chromatography to drug discovery.","authors":"Fotios Tsopelas, Theodosia Vallianatou, Anna Tsantili-Kakoulidou","doi":"10.1080/17460441.2024.2374409","DOIUrl":"10.1080/17460441.2024.2374409","url":null,"abstract":"Introduction: Immobilized artificial membrane (IAM) chromatography is widely used in many aspects of drug discovery. It employs stationary phases, which contain phospholipids combining simulation of biological membranes with rapid measurements.Areas covered: Advances in IAM stationary phases, chromatographic conditions and the underlying retention mechanism are discussed. The potential of IAM chromatography to model permeability and drug-membrane interactions as well as its use to estimate pharmacokinetic properties and toxicity endpoints including ecotoxicity, is outlined. Efforts to construct models for prediction IAM retention factors are presented.Expert opinion: IAM chromatography, as a border case between partitioning and binding, has broadened its application from permeability studies to encompass processes involving tissue binding. Most IAM-based permeability models are hybrid models incorporating additional molecular descriptors, while for the estimation of pharmacokinetic properties and binding to off targets, IAM retention is combined with other biomimetic properties. However, for its integration into routine drug discovery protocols, reliable IAM prediction models implemented in relevant software should be developed, to enable its use in virtual screening and the design of new molecules. Conversely, preparation of new IAM columns with different phospholipids or mixed monomers offers enhanced flexibility and the potential to tailor the conditions according to the target property.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1087-1098"},"PeriodicalIF":6.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491520","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

Inhibitors and PROTACs of CDK2: challenges and opportunities. CDK2 的抑制剂和 PROTACs：挑战与机遇。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-09-01 Epub Date: 2024-07-12 DOI: 10.1080/17460441.2024.2376655

Yangjie Zeng, Xiaodong Ren, Pengyao Jin, Zhida Fan, Mengguang Liu, Yali Zhang, Linzhao Li, Ming Zhuo, Jubo Wang, Zhiyu Li, Min Wu

{"title":"Inhibitors and PROTACs of CDK2: challenges and opportunities.","authors":"Yangjie Zeng, Xiaodong Ren, Pengyao Jin, Zhida Fan, Mengguang Liu, Yali Zhang, Linzhao Li, Ming Zhuo, Jubo Wang, Zhiyu Li, Min Wu","doi":"10.1080/17460441.2024.2376655","DOIUrl":"10.1080/17460441.2024.2376655","url":null,"abstract":"Introduction: Abundant evidence suggests that the overexpression of CDK2-cyclin A/E complex disrupts normal cell cycle regulation, leading to uncontrolled proliferation of cancer cells. Thus, CDK2 has become a promising therapeutic target for cancer treatment. In recent years, insights into the structures of the CDK2 catalytic site and allosteric pockets have provided notable opportunities for developing more effective clinical candidates of CDK2 inhibitors.Area covered: This article reviews the latest CDK2 inhibitors that have entered clinical trials and discusses the design and discovery of the most promising new preclinical CDK2 inhibitors in recent years. Additionally, it summarizes the development of allosteric CDK2 inhibitors and CDK2-targeting PROTACs. The review encompasses strategies for inhibitor and PROTAC design, structure-activity relationships, as well as in vitro and in vivo biological assessments.Expert opinion: Despite considerable effort, no CDK2 inhibitor has yet received FDA approval for marketing due to poor selectivity and observed toxicity in clinical settings. Future research must prioritize the optimization of the selectivity, potency, and pharmacokinetics of CDK2 inhibitors and PROTACs. Moreover, exploring combination therapies incorporating CDK2 inhibitors with other targeted agents, or the design of multi-target inhibitors, presents significant promise for advancing cancer treatment strategies.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1125-1148"},"PeriodicalIF":6.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590072","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

Innovative drug discovery strategies in epilepsy: integrating next-generation syndrome-specific mouse models to address pharmacoresistance and epileptogenesis. 癫痫的创新药物发现策略：整合下一代综合征特异性小鼠模型，解决抗药性和癫痫发生问题。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-09-01 Epub Date: 2024-07-29 DOI: 10.1080/17460441.2024.2384455

Melissa Barker-Haliski, Nicole A Hawkins

{"title":"Innovative drug discovery strategies in epilepsy: integrating next-generation syndrome-specific mouse models to address pharmacoresistance and epileptogenesis.","authors":"Melissa Barker-Haliski, Nicole A Hawkins","doi":"10.1080/17460441.2024.2384455","DOIUrl":"10.1080/17460441.2024.2384455","url":null,"abstract":"Introduction: Although there are numerous treatment options already available for epilepsy, over 30% of patients remain resistant to these antiseizure medications (ASMs). Historically, ASM discovery has relied on the demonstration of efficacy through the use of 'traditional' acute in vivo seizure models (e.g. maximal electroshock, subcutaneous pentylenetetrazol, and kindling). However, advances in genetic sequencing technologies and remaining medical needs for people with treatment-resistant epilepsy or special patient populations have encouraged recent efforts to identify novel compounds in syndrome-specific models of epilepsy. Syndrome-specific models, including Scn1a variant models of Dravet syndrome and APP/PS1 mice associated with familial early-onset Alzheimer's disease, have already led to the discovery of two mechanistically novel treatments for developmental and epileptic encephalopathies (DEEs), namely cannabidiol and soticlestat, respectively.Areas covered: In this review, the authors discuss how it is likely that next-generation drug discovery efforts for epilepsy will more comprehensively integrate syndrome-specific epilepsy models into early drug discovery providing the reader with their expert perspectives.Expert opinion: The percentage of patients with pharmacoresistant epilepsy has remained unchanged despite over 30 marketed ASMs. Consequently, there is a high unmet need to reinvent and revise discovery strategies to more effectively address the remaining needs of patients with specific epilepsy syndromes, including drug-resistant epilepsy and DEEs.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1099-1113"},"PeriodicalIF":6.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0