Expert Opinion on Drug Discovery最新文献_第10页

Advancements in the use of xenopus oocytes for modelling neurological disease for novel drug discovery. 利用爪蟾卵母细胞模拟神经疾病以发现新药的进展。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-02-01 DOI: 10.1080/17460441.2023.2270902

Eoin C O'Connor, Kumiko Kambara, Daniel Bertrand

{"title":"Advancements in the use of xenopus oocytes for modelling neurological disease for novel drug discovery.","authors":"Eoin C O'Connor, Kumiko Kambara, Daniel Bertrand","doi":"10.1080/17460441.2023.2270902","DOIUrl":"10.1080/17460441.2023.2270902","url":null,"abstract":"Introduction: Introduced about 50 years ago, the model of Xenopus oocytes for the expression of recombinant proteins has gained a broad spectrum of applications. The authors herein review the benefits brought from using this model system, with a focus on modeling neurological disease mechanisms and application to drug discovery.Areas covered: Using multiple examples spanning from ligand gated ion channels to transporters, this review presents, in the light of the latest publications, the benefits offered from using Xenopus oocytes. Studies range from the characterization of gene mutations to the discovery of novel treatments for disorders of the central nervous system (CNS).Expert opinion: Development of new drugs targeting CNS disorders has been marked by failures in the translation from preclinical to clinical studies. As progress in genetics and molecular biology highlights large functional differences arising from a single to a few amino acid exchanges, the need for drug screening and functional testing against human proteins is increasing. The use of Xenopus oocytes to enable precise modeling and characterization of clinically relevant genetic variants constitutes a powerful model system that can be used to inform various aspects of CNS drug discovery and development.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233724","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

Current strategic trends in drug discovery: the present as prologue. 药物发现的当前战略趋势：以现在为开端。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-02-01 DOI: 10.1080/17460441.2023.2275640

David R Janero

{"title":"Current strategic trends in drug discovery: the present as prologue.","authors":"David R Janero","doi":"10.1080/17460441.2023.2275640","DOIUrl":"10.1080/17460441.2023.2275640","url":null,"abstract":"Introduction: Escalating costs and inherent uncertainties associated with drug discovery invite initiatives to improve its efficiency and de-risk campaigns for inventing better therapeutics. One such initiative involves recognizing and exploiting current approaches in therapeutics invention with molecular mechanisms of action that hold promise for designing and targeting new chemical entities as drugs.Areas covered: This perspective considers the current contextual framework around three drug-discovery approaches and evaluates their potential to help identify new targets/modalities in small-molecule molecular pharmacology: diversifying ligand-directed phenotypes for G protein-coupled receptor (GPCR) pharmacotherapeutic signaling; developing therapeutic-protein degraders and stabilizers for proximity-inducing pharmacology; and mining organelle biology for druggable therapeutic targets.Expert opinion: The contemporary drug-discovery approaches examined appear generalizable and versatile to have applications in therapeutics invention beyond those case studies discussed herein. Accordingly, they may be considered strategic trends worthy of note in advancing the field toward novel ways of addressing pharmacotherapeutically unmet medical needs.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479890","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 can we unlock the full potential of marine biological resources for novel drug discovery in an effective and ethical way? 我们如何才能以有效和合乎道德的方式释放海洋生物资源的全部潜力，以发现新药?

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-02-01 DOI: 10.1080/17460441.2023.2285402

Hidayat Hussain

引用次数: 0

Advances in drug structure-activity-relationships for the development of selenium-based compounds against HIV. 硒基抗HIV药物构效关系研究进展。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-02-01 DOI: 10.1080/17460441.2023.2284830

Dazhou Shi, Shujing Xu, Dang Ding, Kai Tang, Yang Zhou, Xiangyi Jiang, Shuo Wang, Xinyong Liu, Peng Zhan

{"title":"Advances in drug structure-activity-relationships for the development of selenium-based compounds against HIV.","authors":"Dazhou Shi, Shujing Xu, Dang Ding, Kai Tang, Yang Zhou, Xiangyi Jiang, Shuo Wang, Xinyong Liu, Peng Zhan","doi":"10.1080/17460441.2023.2284830","DOIUrl":"10.1080/17460441.2023.2284830","url":null,"abstract":"Introduction: Selenium possesses numerous advantageous properties in the field of medicine, and a variety of selenium-containing compounds have been documented to exhibit anti-HIV activity. This paper aims to categorize these compounds and conduct SAR analysis to offer guidance for drug design and optimization.Areas covered: The authors present a comprehensive review of the reported SAR analysis conducted on selenium-based compounds against HIV, accompanied by a concise discussion regarding the pivotal role of selenium in drug development.Expert opinion: In addition to the conventional bioisosterism strategy, advanced strategies such as covalent inhibition, fragment-based growth and drug repositioning can also be incorporated into research on selenium-containing anti-HIV drugs. Ebselen, which acts as an HIV capsid inhibitor, serves as a valuable probe compound for the discovery of novel HIV integrase inhibitors. Furthermore, it is crucial not to underestimate the potential toxicity associated with organic selenium compounds despite no reported instances of severe toxicity.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138176011","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

Benford's Law and distributions for better drug design. Benford定律和更好的药物设计分布。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-02-01 DOI: 10.1080/17460441.2023.2277342

Alfonso T García-Sosa

{"title":"Benford's Law and distributions for better drug design.","authors":"Alfonso T García-Sosa","doi":"10.1080/17460441.2023.2277342","DOIUrl":"10.1080/17460441.2023.2277342","url":null,"abstract":"Introduction: Modern drug discovery incorporates various tools and data, heralding the beginning of the data-driven drug design (DD) era. The distributions of chemical and physical data used for Artificial Intelligence (AI)/Machine Learning (ML) and to drive DD have thus become highly important to be understood and used effectively.Areas covered: The authors perform a comprehensive exploration of the statistical distributions driving the data-intensive era of drug discovery, including Benford's Law in AI/ML-based DD.Expert opinion: As the relevance of data-driven discovery escalates, we anticipate meticulous scrutiny of datasets utilizing principles like Benford's Law to enhance data integrity and guide efficient resource allocation and experimental planning. In this data-driven era of the pharmaceutical and medical industries, addressing critical aspects such as bias mitigation, algorithm effectiveness, data stewardship, effects, and fraud prevention are essential. Harnessing Benford's Law and other distributions and statistical tests in DD provides a potent strategy to detect data anomalies, fill data gaps, and enhance dataset quality. Benford's Law is a fast method for data integrity and quality of datasets, the backbone of AI/ML and other modeling approaches, proving very useful in the design process.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71422170","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

Evaluating physiochemical properties of FDA-approved orally administered drugs. 评估美国食品药品监督管理局批准的口服药物的理化性质。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-02-01 DOI: 10.1080/17460441.2023.2275617

Tanner C Reese, Anvita Devineni, Tristan Smith, Ismail Lalami, Jung-Mo Ahn, Ganesh V Raj

{"title":"Evaluating physiochemical properties of FDA-approved orally administered drugs.","authors":"Tanner C Reese, Anvita Devineni, Tristan Smith, Ismail Lalami, Jung-Mo Ahn, Ganesh V Raj","doi":"10.1080/17460441.2023.2275617","DOIUrl":"10.1080/17460441.2023.2275617","url":null,"abstract":"Introduction: Analyses of orally administered FDA-approved drugs from 1990 to 1993 enabled the identification of a set of physiochemical properties known as Lipinski's Rule of Five (Ro5). The original Ro5 and extended versions still remain the reference criteria for drug development programs. Since many bioactive compounds do not conform to the Ro5, we validated the relevance of and adherence to these rulesets in a contemporary cohort of FDA-approved drugs.Areas covered: The authors noted that a significant proportion of FDA-approved orally administered parent compounds from 2011 to 2022 deviate from the original Ro5 criteria (~38%) or the Ro5 with extensions (~53%). They then evaluated if a contemporary Ro5 criteria (cRo5) could be devised to better predict oral bioavailability. Furthermore, they discuss many case studies showcasing the need for and benefit of increasing the size of certain compounds and cover several evolving strategies for improving oral bioavailability.Expert opinion: Despite many revisions to the Ro5, the authors find that no single proposed physiochemical rule has universal concordance with absolute oral bioavailability. Innovations in drug delivery and formulation have dramatically expanded the range of physicochemical properties and the chemical diversity for oral administration.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71422171","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 applications of positron emission tomographic (PET) imaging in psychiatric drug discovery. 正电子发射断层成像（PET）在精神药物发现中的最新应用。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-02-01 DOI: 10.1080/17460441.2023.2278635

Luc Zimmer

{"title":"Recent applications of positron emission tomographic (PET) imaging in psychiatric drug discovery.","authors":"Luc Zimmer","doi":"10.1080/17460441.2023.2278635","DOIUrl":"10.1080/17460441.2023.2278635","url":null,"abstract":"Introduction: Psychiatry is one of the medical disciplines that suffers most from a lack of innovation in its therapeutic arsenal. Many failures in drug candidate trials can be explained by pharmacological properties that have been poorly assessed upstream, in terms of brain passage, brain target binding and clinical outcomes. Positron emission tomography can provide pharmacokinetic and pharmacodynamic data to help select candidate-molecules for further clinical trials.Areas covered: This review aims to explain and discuss the various methods using positron-emitting radiolabeled molecules to trace the cerebral distribution of the drug-candidate or indirectly measure binding to its therapeutic target. More than an exhaustive review of PET studies in psychopharmacology, this article highlights the contributions this technology can make in drug discovery applied to psychiatry.Expert opinion: PET neuroimaging is the only technological approach that can, in vivo in humans, measure cerebral delivery of a drug candidate, percentage and duration of target binding, and even the pharmacological effects. PET studies in a small number of subjects in the early stages of the development of a psychotropic drug can therefore provide the pharmacokinetic/pharmacodynamic data required for subsequent clinical evaluation. While PET technology is demanding in terms of radiochemical, radiopharmacological and nuclear medicine expertise, its integration into the development process of new drugs for psychiatry has great added value.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72014063","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

Current views on in vivo models for breast cancer research and related drug development. 关于乳腺癌研究和相关药物开发的体内模型的当前观点。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-02-01 DOI: 10.1080/17460441.2023.2293152

Tiago Ferreira, Tiago Azevedo, Jessica Silva, Ana I Faustino-Rocha, Paula A Oliveira

{"title":"Current views on in vivo models for breast cancer research and related drug development.","authors":"Tiago Ferreira, Tiago Azevedo, Jessica Silva, Ana I Faustino-Rocha, Paula A Oliveira","doi":"10.1080/17460441.2023.2293152","DOIUrl":"10.1080/17460441.2023.2293152","url":null,"abstract":"Introduction: Animal models play a crucial role in breast cancer research, in particular mice and rats, who develop mammary tumors that closely resemble their human counterparts. These models allow the study of mechanisms behind breast carcinogenesis, as well as the efficacy and safety of new, and potentially more effective and advantageous therapeutic approaches. Understanding the advantages and disadvantages of each model is crucial to select the most appropriate one for the research purpose.Area covered: This review provides a concise overview of the animal models available for breast cancer research, discussing the advantages and disadvantages of each one for searching new and more effective approaches to treatments for this type of cancer.Expert opinion: Rodent models provide valuable information on the genetic alterations of the disease, the tumor microenvironment, and allow the evaluation of the efficacy of chemotherapeutic agents. However, in vivo models have limitations, and one of them is the fact that they do not fully mimic human diseases. Choosing the most suitable model for the study purpose is crucial for the development of new therapeutic agents that provide better care for breast cancer patients.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138794526","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

Successfully navigating the valley of death: the importance of accelerators to support academic drug discovery and development. 成功地导航死亡之谷:加速器对支持学术药物发现和开发的重要性。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-02-01 DOI: 10.1080/17460441.2023.2284824

Maaike Everts, Mark Drew

{"title":"Successfully navigating the valley of death: the importance of accelerators to support academic drug discovery and development.","authors":"Maaike Everts, Mark Drew","doi":"10.1080/17460441.2023.2284824","DOIUrl":"10.1080/17460441.2023.2284824","url":null,"abstract":"Introduction: The drug discovery and development 'valley of death' remains a challenge for promising new therapies originating from academic research laboratories. Drug discovery support centers and accelerators have been established to provide monetary and scientific support, but limited available funding along with cultural and expertise gaps remain obstacles for many promising technologies.Areas covered: In this meta-opinion article, the authors summarize the literature around obstacles that academic drug discovery projects face, along with potential solutions and best practices. Topics covered include funding challenges, regulatory education, reproducibility, along with cultural and organizational considerations. It describes one accelerator in particular-Critical Path Institute's Translational Therapeutics Accelerator (TRxA)-that aims to overcome several of the mentioned challenges.Expert opinion: The 'valley of death' remains a stubborn but not insurmountable part of the academic drug discovery and development landscape. Purposely designed accelerators can help, complementing more traditional intra- and extramural funding support.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648757","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 problem of antimalarial resistance and its implications for drug discovery. 抗疟药物抗药性问题及其对药物研发的影响。

IF 6.3 2区医学

Expert Opinion on Drug Discovery Pub Date : 2024-02-01 DOI: 10.1080/17460441.2023.2284820

Thomas Martin Schäfer, Lais Pessanha de Carvalho, Juliana Inoue, Andrea Kreidenweiss, Jana Held

{"title":"The problem of antimalarial resistance and its implications for drug discovery.","authors":"Thomas Martin Schäfer, Lais Pessanha de Carvalho, Juliana Inoue, Andrea Kreidenweiss, Jana Held","doi":"10.1080/17460441.2023.2284820","DOIUrl":"10.1080/17460441.2023.2284820","url":null,"abstract":"Introduction: Malaria remains a devastating infectious disease with hundreds of thousands of casualties each year. Antimalarial drug resistance has been a threat to malaria control and elimination for many decades and is still of concern today. Despite the continued effectiveness of current first-line treatments, namely artemisinin-based combination therapies, the emergence of drug-resistant parasites in Southeast Asia and even more alarmingly the occurrence of resistance mutations in Africa is of great concern and requires immediate attention.Areas covered: A comprehensive overview of the mechanisms underlying the acquisition of drug resistance in Plasmodium falciparum is given. Understanding these processes provides valuable insights that can be harnessed for the development and selection of novel antimalarials with reduced resistance potential. Additionally, strategies to mitigate resistance to antimalarial compounds on the short term by using approved drugs are discussed.Expert opinion: While employing strategies that utilize already approved drugs may offer a prompt and cost-effective approach to counter antimalarial drug resistance, it is crucial to recognize that only continuous efforts into the development of novel antimalarial drugs can ensure the successful treatment of malaria in the future. Incorporating resistance propensity assessment during this developmental process will increase the likelihood of effective and enduring malaria treatments.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":null,"pages":null},"PeriodicalIF":6.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138794686","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