Nature Reviews. Drug Discovery最新文献_第4页

Understanding anellovirus immune evasion 了解无肠病毒的免疫逃避

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-09-06 DOI: 10.1038/d41573-024-00140-1

Sarah Crunkhorn

引用次数: 0

Protein isoform-centric therapeutics: expanding targets and increasing specificity 以蛋白质同工酶为中心的疗法：扩大靶点，提高特异性

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-09-04 DOI: 10.1038/s41573-024-01025-z

Peter Kjer-Hansen, Tri Giang Phan, Robert J. Weatheritt

{"title":"Protein isoform-centric therapeutics: expanding targets and increasing specificity","authors":"Peter Kjer-Hansen, Tri Giang Phan, Robert J. Weatheritt","doi":"10.1038/s41573-024-01025-z","DOIUrl":"10.1038/s41573-024-01025-z","url":null,"abstract":"Most protein-coding genes produce multiple protein isoforms; however, these isoforms are commonly neglected in drug discovery. The expression of protein isoforms can be specific to a disease, tissue and/or developmental stage, and this specific expression can be harnessed to achieve greater drug specificity than pan-targeting of all gene products and to enable improved treatments for diseases caused by aberrant protein isoform production. In recent years, several protein isoform-centric therapeutics have been developed. Here, we collate these studies and clinical trials to highlight three distinct but overlapping modes of action for protein isoform-centric drugs: isoform switching, isoform introduction or depletion, and modulation of isoform activity. In addition, we discuss how protein isoforms can be used clinically as targets for cell type-specific drug delivery and immunotherapy, diagnostic biomarkers and sources of cancer neoantigens. Collectively, we emphasize the value of a focus on isoforms as a route to discovering drugs with greater specificity and fewer adverse effects. This approach could enable the targeting of proteins for which pan-inhibition of all isoforms is toxic and poorly tolerated. Multiple protein isoforms arise from most genes by alternative RNA splicing and other mechanisms, but these isoforms are often neglected in drug discovery. This Review discusses the modes of action of emerging therapeutics that focus on protein isoforms as well as how isoforms can serve as biomarkers and facilitate targeted drug delivery.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":null,"pages":null},"PeriodicalIF":122.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Engineered parasite delivers proteins to the brain 工程寄生虫向大脑输送蛋白质

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-08-23 DOI: 10.1038/d41573-024-00137-w

Sarah Crunkhorn

引用次数: 0

Degrading cell-free DNA to prevent recurrent stroke 降解无细胞 DNA 以预防中风复发

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-08-22 DOI: 10.1038/d41573-024-00136-x

Alex Eccleston

引用次数: 0

FDA approves first TCR-engineered T cell therapy, for rare soft-tissue cancer FDA 批准首款 TCR 工程 T 细胞疗法，用于治疗罕见软组织癌症

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-08-16 DOI: 10.1038/d41573-024-00134-z

Asher Mullard

引用次数: 0

FDA approves IDH1 and IDH2 inhibitor for brain cancer 美国食品和药物管理局批准用于治疗脑癌的 IDH1 和 IDH2 抑制剂

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-08-16 DOI: 10.1038/d41573-024-00135-y

Asher Mullard

引用次数: 0

A golden age of muscarinic acetylcholine receptor modulation in neurological diseases 神经系统疾病中毒蕈碱乙酰胆碱受体调节的黄金时代。

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-08-14 DOI: 10.1038/s41573-024-01007-1

Andrew B. Tobin

{"title":"A golden age of muscarinic acetylcholine receptor modulation in neurological diseases","authors":"Andrew B. Tobin","doi":"10.1038/s41573-024-01007-1","DOIUrl":"10.1038/s41573-024-01007-1","url":null,"abstract":"Over the past 40 years, the muscarinic acetylcholine receptor family, particularly the M1-receptor and M4-receptor subtypes, have emerged as validated targets for the symptomatic treatment of neurological diseases such as schizophrenia and Alzheimer disease. However, despite considerable effort and investment, no drugs have yet gained clinical approval. This is largely attributable to cholinergic adverse effects that have halted the majority of programmes and resulted in a waning of interest in these G-protein-coupled receptor targets. Recently, this trend has been reversed. Driven by advances in structure-based drug design and an appreciation of the optimal pharmacological properties necessary to deliver clinical efficacy while minimizing adverse effects, a new generation of M1-receptor and M4-receptor orthosteric agonists and positive allosteric modulators are now entering the clinic. These agents offer the prospect of novel therapeutic solutions for ‘hard to treat’ neurological diseases, heralding a new era of muscarinic drug discovery. The M1 and M4 muscarinic acetylcholine receptors represent promising therapeutic targets for Alzheimer disease and schizophrenia. However, the development of agents targeting these receptors has been limited by their adverse cholinergic effects. Here, Tobin discusses how recent advances in the field — including an increased understanding of receptor biology and signalling, as well as the application of structure-based drug design — are enabling a new generation of muscarinic receptor modulators to enter clinical development.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":null,"pages":null},"PeriodicalIF":122.7,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Comprehensive measurement of biopharmaceutical R&D investment 全面衡量生物制药研发投资

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-08-06 DOI: 10.1038/d41573-024-00131-2

Amitabh Chandra, John Drum, Michael Daly, Henry Mirsberger, Samuel Spare, Ulrich Neumann, Silas Martin, Noam Kirson

引用次数: 0

Per-patient approach to calculating drug development costs yields lower estimate 按患者人数计算药物开发成本的方法得出了较低的估算值

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-08-05 DOI: 10.1038/d41573-024-00130-3

Asher Mullard

引用次数: 0

Anti-IL-11 antibody shows anti-ageing properties 抗 IL-11 抗体具有抗衰老特性。

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-08-01 DOI: 10.1038/d41573-024-00132-1

Alex Eccleston

引用次数: 0