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Early career researchers’ experiences in drug discovery in Africa 非洲早期职业研究人员在药物研发方面的经验。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-18 DOI: 10.1016/j.drudis.2024.104183
Godfrey Mayoka, Peter Mubanga Cheuka
{"title":"Early career researchers’ experiences in drug discovery in Africa","authors":"Godfrey Mayoka, Peter Mubanga Cheuka","doi":"10.1016/j.drudis.2024.104183","DOIUrl":"10.1016/j.drudis.2024.104183","url":null,"abstract":"","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104183"},"PeriodicalIF":6.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277766","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
Unveiling the potential of molecular imprinting polymer-based composites in the discovery of advanced drug delivery carriers 揭示分子印迹聚合物基复合材料在发现先进药物输送载体方面的潜力。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-16 DOI: 10.1016/j.drudis.2024.104164
Amit Kumar , Shashi Kashyap , Farhan Mazahir , Rajeev Sharma , Awesh K. Yadav
{"title":"Unveiling the potential of molecular imprinting polymer-based composites in the discovery of advanced drug delivery carriers","authors":"Amit Kumar ,&nbsp;Shashi Kashyap ,&nbsp;Farhan Mazahir ,&nbsp;Rajeev Sharma ,&nbsp;Awesh K. Yadav","doi":"10.1016/j.drudis.2024.104164","DOIUrl":"10.1016/j.drudis.2024.104164","url":null,"abstract":"<div><div>Molecularly imprinted polymers (MIPs) are polymeric matrices that can mimic natural recognition entities, such as antibodies and biological receptors. Molecular imprinting of therapeutics is very appealing in the design of drug delivery systems since the specific and selective binding sites created within the polymeric matrix turn these complex structures into value-added carriers with tunable features, notably high drug-loading capacity and good control of payload release. MIPs possess considerable promise as synthetic recognition elements in ‘theranostics’. Moreover, the high affinity and specificity of MIPs make them more advantageous than other polymer-based nanocomposites. This review summarizes the present state-of-the-art of MIP-based delivery systems for the targeted delivery of bioactives, with current challenges and future perspectives.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104164"},"PeriodicalIF":6.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277770","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 regulatory mechanism of natural polysaccharides in type 2 diabetes mellitus treatment 天然多糖在 2 型糖尿病治疗中的调节机制
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-14 DOI: 10.1016/j.drudis.2024.104182
Surina Bo , Mu Dan , Wei Li , Chen Chen
{"title":"The regulatory mechanism of natural polysaccharides in type 2 diabetes mellitus treatment","authors":"Surina Bo ,&nbsp;Mu Dan ,&nbsp;Wei Li ,&nbsp;Chen Chen","doi":"10.1016/j.drudis.2024.104182","DOIUrl":"10.1016/j.drudis.2024.104182","url":null,"abstract":"<div><div>Diabetes is a complex, multifactorial disease that is caused by a pathological combination of insulin resistance and pancreatic islet dysfunction. Polysaccharides are extensively dispersed in nature and have a very complicated structure with various biological properties. Natural polysaccharides have potentially extraordinary beneficial health effects on managing metabolic diseases such as diabetes, obesity and cardiovascular disease. Thus, a systematic review of the latest research into and possible regulatory mechanisms of natural polysaccharides for type 2 diabetes mellitus treatment is of great significance for a better understanding of their pharmaceutical value. We discuss the regulatory mechanisms of natural polysaccharides for the treatment of diabetes, and especially their role in reshaping dysfunctional gut microbiota. Natural polysaccharides could be developed as new and safe antidiabetic drugs, and detailed mechanistic studies could further clarify the molecular targets of polysaccharides in the treatment of diabetes.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104182"},"PeriodicalIF":6.5,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359644624003076/pdfft?md5=0e0518270b681b81f1885e4f5c0b10f9&pid=1-s2.0-S1359644624003076-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258637","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
Regulatory readiness to facilitate the appropriate use of innovation in clinical trials: The case of decentralized clinical trial approaches 为促进在临床试验中适当利用创新做好监管准备：分散式临床试验方法
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-14 DOI: 10.1016/j.drudis.2024.104180
Amos J. de Jong , Mira G.P. Zuidgeest , Yared Santa-Ana-Tellez , Anthonius de Boer , Helga Gardarsdottir , the Trials@Home Consortium
{"title":"Regulatory readiness to facilitate the appropriate use of innovation in clinical trials: The case of decentralized clinical trial approaches","authors":"Amos J. de Jong ,&nbsp;Mira G.P. Zuidgeest ,&nbsp;Yared Santa-Ana-Tellez ,&nbsp;Anthonius de Boer ,&nbsp;Helga Gardarsdottir ,&nbsp;the Trials@Home Consortium","doi":"10.1016/j.drudis.2024.104180","DOIUrl":"10.1016/j.drudis.2024.104180","url":null,"abstract":"<div><div>Methodological and operational clinical trial innovation is needed to address key challenges associated with clinical trials, including limited generalizability and (s)low recruitment rates. In this article, we discuss how appropriate implementation of innovative clinical trial approaches can be facilitated by a timely identification of, and response to, emerging situations and innovation by regulators (i.e. regulatory readiness) using decentralized clinical trial (DCT) approaches – in which trial activities are moved closer to participants and away from the investigative sites – as a case study example. Specifically, we discuss how explorative research (e.g. using regulatory sandboxes) can enable the collection of data on the usefulness of DCT approaches. Additionally, we argue that DCT approaches should be evaluated similarly to conventional clinical trials.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104180"},"PeriodicalIF":6.5,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359644624003052/pdfft?md5=54070be5f10ff3de1fbc2a29a874ccde&pid=1-s2.0-S1359644624003052-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258638","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
Expression, regulation, and function of PD-L1 on non-tumor cells in the tumor microenvironment 肿瘤微环境中非肿瘤细胞上 PD-L1 的表达、调节和功能
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-13 DOI: 10.1016/j.drudis.2024.104181
Lingrong Hu , Chengliang Sun , Kai Yuan , Peng Yang
{"title":"Expression, regulation, and function of PD-L1 on non-tumor cells in the tumor microenvironment","authors":"Lingrong Hu ,&nbsp;Chengliang Sun ,&nbsp;Kai Yuan ,&nbsp;Peng Yang","doi":"10.1016/j.drudis.2024.104181","DOIUrl":"10.1016/j.drudis.2024.104181","url":null,"abstract":"<div><div>Antiprogrammed death ligand 1 (PD-L1) therapy is a leading immunotherapy, but only some patients with solid cancers benefit. Overwhelming evidence has revealed that PD-L1 is expressed on various immune cells in the tumor microenvironment (TME), including macrophages, dendritic cells, and regulatory T cells, modulating tumor immunity and influencing tumor progression. PD-L1 can also be located on tumor cell membranes as well as in exosomes and cytoplasm. Accordingly, the dynamic expression and various forms of PD-L1 might explain the therapy’s limited efficacy and resistance. Herein a systematic summary of the expression of PD-L1 on different immune cells and their regulatory mechanisms is provided to offer a solid foundation for future studies.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104181"},"PeriodicalIF":6.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258639","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
MicroRNAs and therapeutic potentials in acute and chronic cardiac disease 急性和慢性心脏病中的微 RNA 和治疗潜力
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-12 DOI: 10.1016/j.drudis.2024.104179
Rui Song, Lubo Zhang
{"title":"MicroRNAs and therapeutic potentials in acute and chronic cardiac disease","authors":"Rui Song,&nbsp;Lubo Zhang","doi":"10.1016/j.drudis.2024.104179","DOIUrl":"10.1016/j.drudis.2024.104179","url":null,"abstract":"<div><p>microRNAs (miRNAs) are small regulatory RNAs implicated in various cardiac disorders. In this review, the role of miRNAs is discussed in relation to acute myocardial infarction and chronic heart failure. In both settings, miRNAs are altered, contributing to injury and adverse remodeling. Notably, miRNA profiles differ between acute ischemic injury and progressive heart failure. Owing to miRNA variabilities between disease stages and delivery difficulties, translation of animal studies to the clinic remains challenging. The identification of distinct miRNA signatures could lead to the development of miRNA therapies tailored to different disease stages. Here, we summarize the current understanding of miRNAs in acute and chronic cardiac diseases, identify knowledge gaps and discuss progress in developing miRNA-based treatment strategies.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104179"},"PeriodicalIF":6.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359644624003040/pdfft?md5=0a00fedfa19b4c6cd48de16392cfbb81&pid=1-s2.0-S1359644624003040-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258640","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
Targeted protein degradation: current molecular targets, localization, and strategies 靶向蛋白质降解：当前的分子靶点、定位和策略
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-12 DOI: 10.1016/j.drudis.2024.104178
Dimanthi Pliatsika, Cindy Blatter, Rainer Riedl
{"title":"Targeted protein degradation: current molecular targets, localization, and strategies","authors":"Dimanthi Pliatsika,&nbsp;Cindy Blatter,&nbsp;Rainer Riedl","doi":"10.1016/j.drudis.2024.104178","DOIUrl":"10.1016/j.drudis.2024.104178","url":null,"abstract":"<div><div>Targeted protein degradation (TPD) has revolutionized drug discovery by selectively eliminating specific proteins within and outside the cellular context. Over the past two decades, TPD has expanded its focus beyond well-established targets, exploring diverse proteins beyond cancer-related ones. This evolution extends the potential of TPD to various diseases. Notably, TPD can target proteins at demanding locations, such as the extracellular matrix (ECM) and cellular membranes, presenting both opportunities and challenges for future research. In this review, we comprehensively examine the exciting opportunities in the burgeoning field of TPD, highlighting different targets, their cellular environment, and innovative strategies for modern drug discovery.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104178"},"PeriodicalIF":6.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258642","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
Clinical strategies with antibody–drug conjugates as potential modifications for virotherapy 将抗体药物共轭物作为病毒疗法潜在改良剂的临床策略
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-11 DOI: 10.1016/j.drudis.2024.104165
Zi-Xian Liao , Po-Hsiang Huang , Shan-hui Hsu , Hsiung-Hao Chang , Chi-Heng Chang , S.-Ja Tseng
{"title":"Clinical strategies with antibody–drug conjugates as potential modifications for virotherapy","authors":"Zi-Xian Liao ,&nbsp;Po-Hsiang Huang ,&nbsp;Shan-hui Hsu ,&nbsp;Hsiung-Hao Chang ,&nbsp;Chi-Heng Chang ,&nbsp;S.-Ja Tseng","doi":"10.1016/j.drudis.2024.104165","DOIUrl":"10.1016/j.drudis.2024.104165","url":null,"abstract":"<div><p>The ability to selectively target cancer cells makes antibody–drug conjugates (ADCs) promising therapeutic options. They have been tested in clinical trials as a vehicle for tumor-specific delivery of cytotoxic payloads for a range of cancers. However, systemic administration of oncolytic virotherapy is challenging, because only a small portion of injected viruses reach the target. Despite the approval of higher viral doses, most viruses still end up in the liver, potentially causing toxicity in that organ. Integrating ADCs with virotherapy in the form of antibody–virus conjugates or virus–drug conjugates can potentially overcome these challenges and improve therapeutic outcomes.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104165"},"PeriodicalIF":6.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258641","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
Embryonic and larval zebrafish models for the discovery of new bioactive compounds against tuberculosis 用于发现抗结核新生物活性化合物的胚胎和幼体斑马鱼模型。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-07 DOI: 10.1016/j.drudis.2024.104163
Stella S. Antunes , Gabriel Forn-Cuní , Nelilma C. Romeiro , Herman P. Spaink , Fons J. Verbeek , Michelle F. Muzitano
{"title":"Embryonic and larval zebrafish models for the discovery of new bioactive compounds against tuberculosis","authors":"Stella S. Antunes ,&nbsp;Gabriel Forn-Cuní ,&nbsp;Nelilma C. Romeiro ,&nbsp;Herman P. Spaink ,&nbsp;Fons J. Verbeek ,&nbsp;Michelle F. Muzitano","doi":"10.1016/j.drudis.2024.104163","DOIUrl":"10.1016/j.drudis.2024.104163","url":null,"abstract":"<div><p>Tuberculosis (TB) is a world health challenge the treatment of which is impacted by the rise of drug-resistant strains. Thus, there is an urgent need for new antitubercular compounds and novel approaches to improve current TB therapy. The zebrafish animal model has become increasingly relevant as an experimental system. It has proven particularly useful during early development for aiding TB drug discovery, supporting both the discovery of new insights into mycobacterial pathogenesis and the evaluation of therapeutical toxicity and efficacy <em>in vivo</em>. In this review, we summarize the past two decades of zebrafish–<em>Mycobacterium marinum</em> research and discuss its contribution to the field of bioactive antituberculosis therapy development.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104163"},"PeriodicalIF":6.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152810","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
P-glycoprotein (P-gp)-driven cancer drug resistance: biological profile, non-coding RNAs, drugs and nanomodulators P-糖蛋白（P-gp）驱动的癌症耐药性：生物学概况、非编码 RNA、药物和纳米调节剂。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-07 DOI: 10.1016/j.drudis.2024.104161
Yang Guo , Milad Ashrafizadeh , Murtaza M. Tambuwala , Jun Ren , Gorka Orive , Guiping Yu
{"title":"P-glycoprotein (P-gp)-driven cancer drug resistance: biological profile, non-coding RNAs, drugs and nanomodulators","authors":"Yang Guo ,&nbsp;Milad Ashrafizadeh ,&nbsp;Murtaza M. Tambuwala ,&nbsp;Jun Ren ,&nbsp;Gorka Orive ,&nbsp;Guiping Yu","doi":"10.1016/j.drudis.2024.104161","DOIUrl":"10.1016/j.drudis.2024.104161","url":null,"abstract":"<div><p>Drug resistance has compromised the efficacy of chemotherapy. The dysregulation of drug transporters including P-glycoprotein (P-gp) can mediate drug resistance through drug efflux. In this review, we highlight the role of P-gp in cancer drug resistance and the related molecular pathways, including phosphoinositide 3-kinase (PI3K)–Akt, phosphatase and tensin homolog (PTEN) and nuclear factor-κB (NF-κB), along with non-coding RNAs (ncRNAs). Extracellular vesicles secreted by the cells can transport ncRNAs and other proteins to change P-gp activity in cancer drug resistance. P-gp requires ATP to function, and the induction of mitochondrial dysfunction or inhibition of glutamine metabolism can impair P-gp function, thus increasing chemosensitivity. Phytochemicals, small molecules and nanoparticles have been introduced as P-gp inhibitors to increase drug sensitivity in human cancers.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104161"},"PeriodicalIF":6.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152811","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
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