Nature Reviews Drug Discovery最新文献

Upcoming FDA approval decisions in Q2 2025

Nature Reviews Drug Discovery Pub Date : 2025-03-11 DOI: 10.1038/d41573-025-00050-w

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Engineered nasal bacteria slide drugs into the brain

Nature Reviews Drug Discovery Pub Date : 2025-03-11 DOI: 10.1038/d41573-025-00048-4

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FDA approves CSF1R inhibitor for rare, non-cancerous joint tumours

Nature Reviews Drug Discovery Pub Date : 2025-03-10 DOI: 10.1038/d41573-025-00045-7

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FDA approves MEK inhibitor for rare neurofibromas

Nature Reviews Drug Discovery Pub Date : 2025-03-10 DOI: 10.1038/d41573-025-00044-8

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Bluebird Bio’s cut-price sale highlights challenges for gene therapy field

Nature Reviews Drug Discovery Pub Date : 2025-03-10 DOI: 10.1038/d41573-025-00046-6

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Tumour-agnostic kinase inhibitors

Nature Reviews Drug Discovery Pub Date : 2025-03-06 DOI: 10.1038/s41573-025-01147-y

Jacob J. Adashek, Mina Nikanjam, Razelle Kurzrock

{"title":"Tumour-agnostic kinase inhibitors","authors":"Jacob J. Adashek, Mina Nikanjam, Razelle Kurzrock","doi":"10.1038/s41573-025-01147-y","DOIUrl":"https://doi.org/10.1038/s41573-025-01147-y","url":null,"abstract":"<p>Protein kinases are crucial targets for cancer treatment as they orchestrate important signals for oncogenesis and are often aberrantly activated owing to genomic alterations. In the past two decades, multiple kinase inhibitors have been developed, including those that are clinically effective regardless of tumour location, provided that the tumour harbours the aberrantly activated kinase. Consequently, a biomarker-based therapy model, untethered from tumour histology and organ of origin, has been established, which has led to transformative regulatory approvals of tumour-agnostic kinase inhibitors such as larotrectinib, selpercatinib, dabrafenib–trametinib and pemigatinib. However, almost all such approvals are partial in nature, as they do not include both solid and haematological cancers, even if the kinase inhibitor has shown activity in both. Moreover, clinical trials to assess these compounds are challenging because genomic sequencing of hundreds or thousands of tumours may be required to find eligible patients whose malignancy bears the targeted genetic alterations. In this Review, we describe the precision medicine paradigm that has successfully launched tumour-agnostic drug development, concentrating on small-molecule inhibitors that target kinase pathway aberrations, and we discuss the challenges in developing tumour‐agnostic agents.</p>","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Accelerating adoption of new approach methodologies in regulatory decision making: an industry perspective

Nature Reviews Drug Discovery Pub Date : 2025-03-06 DOI: 10.1038/d41573-025-00038-6

Andrew S. Robertson, Nahid Latif, Imein Bousnina, Donna Boyce, Kevin Carl, Sean P. Curtis, Jennifer Dudinak, Carlos O. Garner, Michael Garvin, Sabine Luik, Eddie Reilly, Michelle Rohrer, Katrin Rupalla, Jacintha Shenton, Jerry Stewart, Mark Taisey, Raymond C. Votzmeyer, Matthew P. Wagoner, Max Wegner, Kathy Williams

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ASO targets DNA repair protein to combat Huntington disease

Nature Reviews Drug Discovery Pub Date : 2025-03-05 DOI: 10.1038/d41573-025-00042-w

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Thirty years of NRF2: advances and therapeutic challenges

Nature Reviews Drug Discovery Pub Date : 2025-03-04 DOI: 10.1038/s41573-025-01145-0

Donna D. Zhang

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GPCR drug discovery: new agents, targets and indications

Nature Reviews Drug Discovery Pub Date : 2025-03-03 DOI: 10.1038/s41573-025-01139-y

Javier Sánchez Lorente, Aleksandr V. Sokolov, Gavin Ferguson, Helgi B. Schiöth, Alexander S. Hauser, David E. Gloriam

{"title":"GPCR drug discovery: new agents, targets and indications","authors":"Javier Sánchez Lorente, Aleksandr V. Sokolov, Gavin Ferguson, Helgi B. Schiöth, Alexander S. Hauser, David E. Gloriam","doi":"10.1038/s41573-025-01139-y","DOIUrl":"https://doi.org/10.1038/s41573-025-01139-y","url":null,"abstract":"<p>G protein-coupled receptors (GPCRs) form one of the largest drug target families, reflecting their involvement in numerous pathophysiological processes. In this Review, we analyse drug discovery trends for the GPCR superfamily, covering compounds, targets and indications that have reached regulatory approval or that are being investigated in clinical trials. We find that there are 516 approved drugs targeting GPCRs, making up 36% of all approved drugs. These drugs act on 121 GPCR targets, one-third of all non-sensory GPCRs. Furthermore, 337 agents targeting 133 GPCRs, including 30 novel targets, are being investigated in clinical trials. Notably, 165 of these agents are approved drugs being tested for additional indications and novel agents are increasingly allosteric modulators and biologics. Remarkably, diabetes and obesity drugs targeting GPCRs had sales of nearly US $30 billion in 2023 and the numbers of clinical trials for GPCR modulators in the metabolic diseases, oncology and immunology areas are increasing strongly. Finally, we highlight the potential of untapped target–disease associations and pathway-biased signalling. Overall, this Review provides an up-to-date reference for the drugged and potentially druggable GPCRome to inform future GPCR drug discovery and development.</p>","PeriodicalId":18847,"journal":{"name":"Nature Reviews Drug Discovery","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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