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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":"29 12","pages":"Article 104209"},"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":"29 12","pages":"Article 104208"},"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":"29 11","pages":"Article 104207"},"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":"29 12","pages":"Article 104206"},"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":"29 12","pages":"Article 104204"},"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":"29 12","pages":"Article 104201"},"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
The rejection that defies antirejection drugs—chronic vascular rejection (allograft vasculopathy): The role of terminology and linguistic relativity 对抗抗排斥药物的排斥反应--慢性血管排斥反应（异体移植物血管病变）：术语和语言相对性的作用。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-09 DOI: 10.1016/j.drudis.2024.104202
Vladimir M. Subbotin , Michael V. Subotin
{"title":"The rejection that defies antirejection drugs—chronic vascular rejection (allograft vasculopathy): The role of terminology and linguistic relativity","authors":"Vladimir M. Subbotin ,&nbsp;Michael V. Subotin","doi":"10.1016/j.drudis.2024.104202","DOIUrl":"10.1016/j.drudis.2024.104202","url":null,"abstract":"<div><div>While allograft loss due to acute rejection has been dramatically reduced due to the introduction of immunophilins, this therapy has little effect on allografts lost due to chronic vascular rejection. This situation may be due to a misnomer of the pathology. Specifically, its designation as ‘chronic rejection’ has given the wrong impression that the cause of the disease has been identified. Analyzing this phenomenon under the rubric of linguistic relativity suggests that the words chosen to name the disease may have restricted our cognitive ability to solve the problem. Thus, we have to step out of the ‘alloimmunity/rejection box’.</div><div> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!-->Let’s pause between our words,</div><div> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!-->Speak and fall silent again,</div><div> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!-->So that the meaning of the word just spoken,</div><div> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!-->Sounds a clearer echo in our heads.</div><div> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!-->Let’s pause between our words.</div><div> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!--> <!-->Andrey Makarevich.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104202"},"PeriodicalIF":6.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398899","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
Utilization of phase I studies for target validation of first-in-class drugs 利用 I 期研究验证同类首创药物的靶点。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-09 DOI: 10.1016/j.drudis.2024.104200
Yoshiki Kawabe, Motomu Himori, Yoshinori Watanabe, Jacob Davis, Hiromasa Hamada
{"title":"Utilization of phase I studies for target validation of first-in-class drugs","authors":"Yoshiki Kawabe,&nbsp;Motomu Himori,&nbsp;Yoshinori Watanabe,&nbsp;Jacob Davis,&nbsp;Hiromasa Hamada","doi":"10.1016/j.drudis.2024.104200","DOIUrl":"10.1016/j.drudis.2024.104200","url":null,"abstract":"<div><div>This review discusses the growing importance of target validation within phase I (P1) trials as a new trend in drug development, especially in establishing proof of concept (POC) for first-in-class drugs. The paper describes two approaches: the P1-PIV approach, which directly evaluates the primary endpoint for a pivotal clinical study to confirm therapeutic effects during P1, and the newly introduced P1-FCTE, which assesses functional changes necessary for therapeutic effect as a novel target validation milestone in P1. By providing practical examples of first-in-class drugs, we compare the benefits, costs, hurdles and applicable therapeutic areas of these approaches. Finally, we discuss the potential of these novel approaches to facilitate POC success, shorten development timelines and ultimately increase drug discovery success rates.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104200"},"PeriodicalIF":6.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386849","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 hallmarks of tissue-agnostic therapies and strategies for early anticancer drug discovery 组织诊断疗法的特点和早期抗癌药物的发现策略。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-09 DOI: 10.1016/j.drudis.2024.104203
Jihyeob Mun , Byungho Lim
{"title":"The hallmarks of tissue-agnostic therapies and strategies for early anticancer drug discovery","authors":"Jihyeob Mun ,&nbsp;Byungho Lim","doi":"10.1016/j.drudis.2024.104203","DOIUrl":"10.1016/j.drudis.2024.104203","url":null,"abstract":"<div><div>Recently, precision medicine has enabled biomarker-driven treatment to be administered in a pan-tumor setting, so-called tissue-agnostic therapy. This represents a paradigm shift in cancer care from conventional cancer type-specific to biomarker-centric care, where patients are selected for this type of therapy based on molecular aberrations that occur across cancer types, regardless of tumor site or histology. This approach is particularly important because it offers new treatment options for patients with rare cancers or for whom there are no adequate treatments. Therefore drug development with the goal of tissue agnosticism can accelerate drug approval and address unmet medical needs. Herein, we discuss our opinions on the hallmarks of tissue-agnostic treatments and propose strategies for early drug discovery based on these hallmarks.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104203"},"PeriodicalIF":6.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398898","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
Polybodies: Next-generation clinical antibodies 多抗体：新一代临床抗体
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-10-05 DOI: 10.1016/j.drudis.2024.104198
Abhay H. Pande , Sandeep , Suraj H. Shinde
{"title":"Polybodies: Next-generation clinical antibodies","authors":"Abhay H. Pande ,&nbsp;Sandeep ,&nbsp;Suraj H. Shinde","doi":"10.1016/j.drudis.2024.104198","DOIUrl":"10.1016/j.drudis.2024.104198","url":null,"abstract":"<div><div>Conventional antibodies [full-length and fragments: F(ab′)<sub>2</sub>, fragment antigen-binding (Fab), single-chain variable fragment (scFv), variable heavy domain of heavy chain antibody (VHH)] are monospecific, first-generation antibodies, that have dominated the biopharmaceuticals field. However, protein engineering approaches has led to the advent of the next-generation antibodies (polybodies), which are significant improvement over the conventional antibodies. Polybodies comprise polyspecific and/or polyvalent antibodies that enable a single antibody to target multiple specific antigens simultaneously. Polybodies are superior to first-generation antibodies (more efficacious, broad-spectrum, resistance resilient, customizable, etc.) and provide a cost-effective healthcare solution. This review addresses recent developments in polybodies, highlighting their superiority over conventional antibodies and offering future perspectives to encourage the generation of innovative immunotherapies.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 12","pages":"Article 104198"},"PeriodicalIF":6.5,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379708","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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