Nature Reviews. Drug Discovery最新文献_第6页

Author Correction: B cell depletion therapies in autoimmune disease: advances and mechanistic insights 作者更正：自身免疫性疾病中的 B 细胞耗竭疗法：进展与机理认识

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-11-26 DOI: 10.1038/s41573-024-01103-2

Dennis S. W. Lee, Olga L. Rojas, Jennifer L. Gommerman

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FDA approves second TTR stabilizer for cardiac amyloidosis 美国食品和药物管理局批准第二种治疗心脏淀粉样变性的 TTR 稳定剂

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-11-25 DOI: 10.1038/d41573-024-00188-z

Asher Mullard

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StitchR platform joins up gene therapy payloads StitchR 平台连接基因治疗有效载荷

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-11-22 DOI: 10.1038/d41573-024-00186-1

Katie Kingwell

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NK2R agonist delivers one-two punch to obesity NK2R激动剂一举击退肥胖症

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-11-21 DOI: 10.1038/d41573-024-00185-2

Sarah Crunkhorn

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Targeting lysine acetylation readers and writers 瞄准赖氨酸乙酰化的读者和作者

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-11-21 DOI: 10.1038/s41573-024-01080-6

Ming-Ming Zhou, Philip A. Cole

{"title":"Targeting lysine acetylation readers and writers","authors":"Ming-Ming Zhou, Philip A. Cole","doi":"10.1038/s41573-024-01080-6","DOIUrl":"10.1038/s41573-024-01080-6","url":null,"abstract":"Lysine acetylation is a major post-translational modification in histones and other proteins that is catalysed by the ‘writer’ lysine acetyltransferases (KATs) and mediates interactions with bromodomains (BrDs) and other ‘reader’ proteins. KATs and BrDs play key roles in regulating gene expression, cell growth, chromatin structure, and epigenetics and are often dysregulated in disease states, including cancer. There have been accelerating efforts to identify potent and selective small molecules that can target individual KATs and BrDs with the goal of developing new therapeutics, and some of these agents are in clinical trials. Here, we summarize the different families of KATs and BrDs, discuss their functions and structures, and highlight key advances in the design and development of chemical agents that show promise in blocking the action of these chromatin proteins for disease treatment. Lysine acetylation is a post-translational modification on histones and other proteins that is catalysed by acetyltransferases (‘writers’) and mediates interactions with bromodomains and other ‘reader’ domains. This Review summarizes the properties and functions of these writers and readers and discusses efforts to identify small-molecule therapeutics that target them, some of which are being evaluated in clinical trials.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"24 2","pages":"112-133"},"PeriodicalIF":122.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142679095","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}

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FDA approves l-amino acid decarboxylase deficiency gene therapy 美国食品和药物管理局批准 L-氨基酸脱羧酶缺乏症基因疗法。

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-11-15 DOI: 10.1038/d41573-024-00184-3

Asher Mullard

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Senescence as a therapeutic target in cancer and age-related diseases 将衰老作为癌症和老年相关疾病的治疗靶点

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-11-15 DOI: 10.1038/s41573-024-01074-4

Domhnall McHugh, Imanol Durán, Jesús Gil

{"title":"Senescence as a therapeutic target in cancer and age-related diseases","authors":"Domhnall McHugh, Imanol Durán, Jesús Gil","doi":"10.1038/s41573-024-01074-4","DOIUrl":"10.1038/s41573-024-01074-4","url":null,"abstract":"Cellular senescence is a stress response that restrains the growth of aged, damaged or abnormal cells. Thus, senescence has a crucial role in development, tissue maintenance and cancer prevention. However, lingering senescent cells fuel chronic inflammation through the acquisition of a senescence-associated secretory phenotype (SASP), which contributes to cancer and age-related tissue dysfunction. Recent progress in understanding senescence has spurred interest in the development of approaches to target senescent cells, known as senotherapies. In this Review, we evaluate the status of various types of senotherapies, including senolytics that eliminate senescent cells, senomorphics that suppress the SASP, interventions that mitigate senescence and strategies that harness the immune system to clear senescent cells. We also summarize how these approaches can be combined with cancer therapies, and we discuss the challenges and opportunities in moving senotherapies into clinical practice. Such therapies have the potential to address root causes of age-related diseases and thus open new avenues for preventive therapies and treating multimorbidities. Recent progress in understanding senescence has spurred interest in the development of approaches that target senescent cells. This Review assesses the current status of senotherapies, such as senolytics and senomorphics, how these approaches can be combined with cancer therapies, and the challenges and opportunities in moving senotherapies to clinical practice.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"24 1","pages":"57-71"},"PeriodicalIF":122.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637120","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}

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DNA damage response inhibitors in cancer therapy: lessons from the past, current status and future implications 癌症治疗中的 DNA 损伤反应抑制剂：过去的教训、现状和未来的影响

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-11-12 DOI: 10.1038/s41573-024-01060-w

Yvette Drew, Frank T Zenke, Nicola J Curtin

{"title":"DNA damage response inhibitors in cancer therapy: lessons from the past, current status and future implications","authors":"Yvette Drew, Frank T Zenke, Nicola J Curtin","doi":"10.1038/s41573-024-01060-w","DOIUrl":"10.1038/s41573-024-01060-w","url":null,"abstract":"The DNA damage response (DDR) is a network of proteins that coordinate DNA repair and cell-cycle checkpoints to prevent damage being transmitted to daughter cells. DDR defects lead to genomic instability, which enables tumour development, but they also create vulnerabilities that can be used for cancer therapy. Historically, this vulnerability has been taken advantage of using DNA-damaging cytotoxic drugs and radiotherapy, which are more toxic to tumour cells than to normal tissues. However, the discovery of the unique sensitivity of tumours defective in the homologous recombination DNA repair pathway to PARP inhibition led to the approval of six PARP inhibitors worldwide and to a focus on making use of DDR defects through the development of other DDR-targeting drugs. Here, we analyse the lessons learnt from PARP inhibitor development and how these may be applied to new targets to maximize success. We explore why, despite so much research, no other DDR inhibitor class has been approved, and only a handful have advanced to later-stage clinical trials. We discuss why more reliable predictive biomarkers are needed, explore study design from past and current trials, and suggest alternative models for monotherapy and combination studies. Targeting multiple DDR pathways simultaneously and potential combinations with anti-angiogenic agents or immune checkpoint inhibitors are also discussed. Defects in the DNA damage response have been utilized therapeutically for cancer for a decade. This Review analyses the lessons learnt from the development of PARP inhibitors and how these may be applied to new targets to maximize success. Targeting multiple DNA damage response pathways simultaneously and combinations with other therapies are also discussed.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"24 1","pages":"19-39"},"PeriodicalIF":122.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599375","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

Benchmarking recruitment rates for phase III trials 第三阶段试验的招募率基准

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-11-08 DOI: 10.1038/d41573-024-00183-4

Subha B. Basu

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Antimalarial drug hits cardiac fibrosis 抗疟药物治疗心脏纤维化

IF 122.7 1区医学

Nature Reviews. Drug Discovery Pub Date : 2024-11-05 DOI: 10.1038/d41573-024-00182-5

M. Teresa Villanueva

引用次数: 0