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Ex vivo permeability study of poorly soluble drugs across gastrointestinal membranes: acceptor compartment media composition. 差溶性药物通过胃肠道膜的体内外渗透性研究：受体区介质成分。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-18 DOI: 10.1016/j.drudis.2024.104214
Andrejs Sitovs, Valentyn Mohylyuk
{"title":"Ex vivo permeability study of poorly soluble drugs across gastrointestinal membranes: acceptor compartment media composition.","authors":"Andrejs Sitovs, Valentyn Mohylyuk","doi":"10.1016/j.drudis.2024.104214","DOIUrl":"10.1016/j.drudis.2024.104214","url":null,"abstract":"<p><p>Ex vivo drug permeability testing across gastrointestinal (GI) membranes is crucial in drug discovery and oral drug delivery. It is a reliable method for drugs with good solubility, but it poses challenges for poorly soluble drugs, which are common in development pipelines today. Although enabling formulations increase the apparent solubility in the GI compartment (dissolution vessel or permeation chamber's donor compartment), maintaining solubilized drug in the acceptor compartment during ex vivo testing remains largely unresolved. This review compiles and critically evaluates the diverse compositions of acceptor media used in ex vivo permeability studies for poorly soluble drugs, highlighting this significant yet underexplored aspect of pharmaceutical science. An algorithm is proposed for selecting solubility-enhancing additives for the acceptor media in ex vivo permeability studies of poorly soluble drugs.</p>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454525","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 Challenges and Opportunities in Clinical Trial Diversity: Mistrust in the healthcare system is a significant barrier to recruitment. 临床试验多样性的挑战与机遇 对医疗系统的不信任是招募人员的一大障碍。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-18 DOI: 10.1016/j.drudis.2024.104210
Lisa Bailey
{"title":"The Challenges and Opportunities in Clinical Trial Diversity: Mistrust in the healthcare system is a significant barrier to recruitment.","authors":"Lisa Bailey","doi":"10.1016/j.drudis.2024.104210","DOIUrl":"10.1016/j.drudis.2024.104210","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454528","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
Environmental risk assessment in the EU regulation of medicines for human use: an analysis of stakeholder perspectives on its current and future role 欧盟人用药品监管中的环境风险评估：利益相关者对其当前和未来作用的观点分析。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-18 DOI: 10.1016/j.drudis.2024.104213
Jim F. Zinken , Anna M.G. Pasmooij , Antwan G.H. Ederveen , Jarno Hoekman , Lourens T. Bloem
{"title":"Environmental risk assessment in the EU regulation of medicines for human use: an analysis of stakeholder perspectives on its current and future role","authors":"Jim F. Zinken ,&nbsp;Anna M.G. Pasmooij ,&nbsp;Antwan G.H. Ederveen ,&nbsp;Jarno Hoekman ,&nbsp;Lourens T. Bloem","doi":"10.1016/j.drudis.2024.104213","DOIUrl":"10.1016/j.drudis.2024.104213","url":null,"abstract":"<div><div>An environmental risk assessment (ERA) is mandatory for all applications for marketing authorisation of medicines in the European Union (EU). We investigated stakeholder perspectives on the role of the ERA in EU regulation of medicines for human use. We discuss the current position of the ERA and the current conduct and assessment of the ERA, such as the required expertise, data, and studies, its applicability to generic drugs, and its use in regulatory decision-making. We also discuss future perspectives, including extension of the ERA to cover antimicrobial resistance, improved risk mitigation, impact on ‘over-the-counter’ (OTC) status, and incorporation into reimbursement considerations.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454524","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
Unlocking therapeutic frontiers: harnessing artificial intelligence in drug discovery for neurodegenerative diseases 开启治疗前沿：利用人工智能发现治疗神经退行性疾病的药物。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-18 DOI: 10.1016/j.drudis.2024.104216
Bilal Nehmeh , Joseph Rebehmed , Riham Nehmeh , Robin Taleb , Elias Akoury
{"title":"Unlocking therapeutic frontiers: harnessing artificial intelligence in drug discovery for neurodegenerative diseases","authors":"Bilal Nehmeh ,&nbsp;Joseph Rebehmed ,&nbsp;Riham Nehmeh ,&nbsp;Robin Taleb ,&nbsp;Elias Akoury","doi":"10.1016/j.drudis.2024.104216","DOIUrl":"10.1016/j.drudis.2024.104216","url":null,"abstract":"<div><div>Neurodegenerative diseases (NDs) pose serious healthcare challenges with limited therapeutic treatments and high social burdens. The integration of artificial intelligence (AI) into drug discovery has emerged as a promising approach to address these challenges. This review explores the application of AI techniques to unravel therapeutic frontiers for NDs. We examine the current landscape of AI-driven drug discovery and discuss the potentials of AI in accelerating the identification of novel therapeutic targets on ND research and drug development, optimization of drug candidates, and expediating personalized medicine approaches. Finally, we outline future directions and challenges in harnessing AI for the advancement of therapeutics in this critical area by emphasizing the importance of interdisciplinary collaboration and ethical considerations.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454530","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
Peptide-based therapeutics targeting genetic disorders 针对遗传疾病的多肽疗法。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-16 DOI: 10.1016/j.drudis.2024.104209
Shweta Subramanian, Meenakshi Jain, Rajkumar Misra, Rahul Jain
{"title":"Peptide-based therapeutics targeting genetic disorders","authors":"Shweta Subramanian,&nbsp;Meenakshi Jain,&nbsp;Rajkumar Misra,&nbsp;Rahul Jain","doi":"10.1016/j.drudis.2024.104209","DOIUrl":"10.1016/j.drudis.2024.104209","url":null,"abstract":"<div><div>Genetic disorders (GDs) are challenging to treat owing to a lack of optimal treatment regimens and intricate and often difficult-to-understand underlying biological processes. Limited therapeutic approaches, which mostly provide symptomatic relief, are available. To date, a limited number of peptide-based drugs for the treatment of GDs are available, and several candidates are under clinical study. This review provides mechanistic insights into GDs and potential target areas where peptide-based drugs are beneficial. In addition, it emphasizes the usefulness of peptides as carriers for gene delivery, biomarkers for mutation detection and peptide-based vaccines for treating GDs.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454526","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, and prospects of, 3D preclinical models for skin drug discovery 用于皮肤药物发现的三维临床前模型的进展和前景。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-11 DOI: 10.1016/j.drudis.2024.104208
Mohammad Imran , Peter Michael Moyle , Danielle Kamato , Yousuf Mohammed
{"title":"Advances in, and prospects of, 3D preclinical models for skin drug discovery","authors":"Mohammad Imran ,&nbsp;Peter Michael Moyle ,&nbsp;Danielle Kamato ,&nbsp;Yousuf Mohammed","doi":"10.1016/j.drudis.2024.104208","DOIUrl":"10.1016/j.drudis.2024.104208","url":null,"abstract":"<div><div>The skin has an important role in regulating homeostasis and protecting the body from endogenous and exogenous microenvironments. Although 3D models for drug discovery have been extensively studied, there is a growing demand for more advanced 3D skin models to enhance skin research. The use of these advanced skin models holds promise across domains such as cosmetics, skin disease treatments, and toxicity testing of new therapeutics. Recent advances include the development of skin-on-a-chip, spheroids, reconstructed skin, organoids, and computational approaches, including quantitative structure–activity relationship (QSAR) and quantitative structure–property relationship (QSPR) research. These innovations are bridging the gap between traditional 2D and advanced 3D models, moving progress from research to clinical applications. In this review, we highlight <em>in vitro</em> and computational skin models with advanced drug discovery for skin-related applications.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454522","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
Drug discovery and development in idiopathic pulmonary fibrosis: the changing landscape 特发性肺纤维化的药物发现与开发：不断变化的形势。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-11 DOI: 10.1016/j.drudis.2024.104207
Simon Cruwys, Peter Hein, Bob Humphries, Darcey Black
{"title":"Drug discovery and development in idiopathic pulmonary fibrosis: the changing landscape","authors":"Simon Cruwys,&nbsp;Peter Hein,&nbsp;Bob Humphries,&nbsp;Darcey Black","doi":"10.1016/j.drudis.2024.104207","DOIUrl":"10.1016/j.drudis.2024.104207","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is an area of high unmet clinical need and high research activity in the pharmaceutical and biotech industries. The two approved therapies, nintedanib and pirfenidone, have issues with efficacy and tolerability. Despite a considerable number of development programs reaching late-stage Phase 2b or 3 clinical trials, no drug other than nintedanib and pirfenidone has successfully demonstrated a benefit for patients. An analysis of these failures, and consideration of the trajectories of some of the current development projects, may offer novel paradigms for choosing modes-of-action and for the development of successful drugs.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454523","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
Peptides as innovative strategies to combat drug resistance in cancer therapy 肽作为抗癌疗法中抗药性的创新策略。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-10 DOI: 10.1016/j.drudis.2024.104206
Henry O. Lamb , Aurélie H. Benfield , Sónia Troeira Henriques
{"title":"Peptides as innovative strategies to combat drug resistance in cancer therapy","authors":"Henry O. Lamb ,&nbsp;Aurélie H. Benfield ,&nbsp;Sónia Troeira Henriques","doi":"10.1016/j.drudis.2024.104206","DOIUrl":"10.1016/j.drudis.2024.104206","url":null,"abstract":"<div><div>Drug resistance is the leading cause of treatment failure in patients with cancer. Thus, innovative therapeutic strategies are required to overcome this critical challenge and improve patient outcomes. In this review, we examine the potential of peptide-based therapies to combat drug resistance in cancer. We highlight the unique strategies and mechanisms that can be explored by using peptides, including their ability to selectively target tumours, facilitate drug delivery into cancer cells, and inhibit key intracellular proteins that drive cancer progression and resistance. Peptides offer a promising approach to overcoming both intrinsic and adaptative cancer resistance against chemotherapy, targeted therapies, and biologics.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454527","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
The Wnt signaling cascade: a potential but untapped therapeutic target for monkeypox infection Wnt信号级联：猴痘感染的潜在但尚未开发的治疗靶点。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-10 DOI: 10.1016/j.drudis.2024.104204
Navid Faraji, Mohammad Abavisani, Amirhossein Sahebkar
{"title":"The Wnt signaling cascade: a potential but untapped therapeutic target for monkeypox infection","authors":"Navid Faraji,&nbsp;Mohammad Abavisani,&nbsp;Amirhossein Sahebkar","doi":"10.1016/j.drudis.2024.104204","DOIUrl":"10.1016/j.drudis.2024.104204","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405789","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
Therapeutic development approaches to treat haploinsufficiency diseases: restoring protein levels 治疗单倍蛋白缺乏疾病的治疗开发方法：恢复蛋白质水平。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-09 DOI: 10.1016/j.drudis.2024.104201
Elena F. Evans , Zeenat A. Shyr , Bryan J. Traynor , Wei Zheng
{"title":"Therapeutic development approaches to treat haploinsufficiency diseases: restoring protein levels","authors":"Elena F. Evans ,&nbsp;Zeenat A. Shyr ,&nbsp;Bryan J. Traynor ,&nbsp;Wei Zheng","doi":"10.1016/j.drudis.2024.104201","DOIUrl":"10.1016/j.drudis.2024.104201","url":null,"abstract":"<div><div>Rare diseases affect one in ten people but only a small fraction of these diseases have an FDA-approved treatment. Haploinsufficiency, caused by a dominant loss-of-function mutation, is a unique rare disease group because patients have one normal allele of the affected gene. This makes rare haploinsufficiency diseases promising candidates for drug development by increasing expression of the normal gene allele, decreasing the target protein degradation and enhancing the target protein function. This review summarizes recent progresses and approaches used in the translational research of therapeutics to treat haploinsufficiency diseases including gene therapy, nucleotide-based therapeutics and small-molecule drug development. We hope that these drug development strategies will accelerate therapeutic development to treat haploinsufficiency diseases.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":null,"pages":null},"PeriodicalIF":6.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386848","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
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