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Trends in pharmacological sciences最新文献

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Mirikizumab (Omvoh™) for ulcerative colitis. 治疗溃疡性结肠炎的米利珠单抗（Omvoh™）。
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-03-01 Epub Date: 2024-01-22 DOI: 10.1016/j.tips.2024.01.001
Alexander Hammerhøj, Theresa Louise Boye, Ebbe Langholz, Ole Haagen Nielsen
{"title":"Mirikizumab (Omvoh™) for ulcerative colitis.","authors":"Alexander Hammerhøj, Theresa Louise Boye, Ebbe Langholz, Ole Haagen Nielsen","doi":"10.1016/j.tips.2024.01.001","DOIUrl":"10.1016/j.tips.2024.01.001","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542178","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
Mitochondrial DNA competition: starving out the mutant genome. 线粒体 DNA 竞争：饿死突变基因组
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-03-01 Epub Date: 2024-02-23 DOI: 10.1016/j.tips.2024.01.011
Antonella Spinazzola, Diego Perez-Rodriguez, Jan Ježek, Ian J Holt
{"title":"Mitochondrial DNA competition: starving out the mutant genome.","authors":"Antonella Spinazzola, Diego Perez-Rodriguez, Jan Ježek, Ian J Holt","doi":"10.1016/j.tips.2024.01.011","DOIUrl":"10.1016/j.tips.2024.01.011","url":null,"abstract":"<p><p>High levels of pathogenic mitochondrial DNA (mtDNA) variants lead to severe genetic diseases, and the accumulation of such mutants may also contribute to common disorders. Thus, selecting against these mutants is a major goal in mitochondrial medicine. Although mutant mtDNA can drift randomly, mounting evidence indicates that active forces play a role in the selection for and against mtDNA variants. The underlying mechanisms are beginning to be clarified, and recent studies suggest that metabolic cues, including fuel availability, contribute to shaping mtDNA heteroplasmy. In the context of pathological mtDNAs, remodeling of nutrient metabolism supports mitochondria with deleterious mtDNAs and enables them to outcompete functional variants owing to a replicative advantage. The elevated nutrient requirement represents a mutant Achilles' heel because small molecules that restrict nutrient consumption or interfere with nutrient sensing can purge cells of deleterious mtDNAs and restore mitochondrial respiration. These advances herald the dawn of a new era of small-molecule therapies to counteract pathological mtDNAs.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944501","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
Recent advances in generative biology for biotherapeutic discovery. 用于生物治疗发现的生成生物学的最新进展。
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-03-01 Epub Date: 2024-02-19 DOI: 10.1016/j.tips.2024.01.003
Marissa Mock, Christopher James Langmead, Peter Grandsard, Suzanne Edavettal, Alan Russell
{"title":"Recent advances in generative biology for biotherapeutic discovery.","authors":"Marissa Mock, Christopher James Langmead, Peter Grandsard, Suzanne Edavettal, Alan Russell","doi":"10.1016/j.tips.2024.01.003","DOIUrl":"10.1016/j.tips.2024.01.003","url":null,"abstract":"<p><p>Generative biology combines artificial intelligence (AI), advanced life sciences technologies, and automation to revolutionize the process of designing novel biomolecules with prescribed properties, giving drug discoverers the ability to escape the limitations of biology during the design of next-generation protein therapeutics. Significant hurdles remain, namely: (i) the inherently complex nature of drug discovery, (ii) the bewildering number of promising computational and experimental techniques that have emerged in the past several years, and (iii) the limited availability of relevant protein sequence-function data for drug-like molecules. There is a need to focus on computational methods that will be most practically effective for protein drug discovery and on building experimental platforms to generate the data most appropriate for these methods. Here, we discuss recent advances in computational and experimental life sciences that are most crucial for impacting the pace and success of protein drug discovery.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913536","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
Targeting chromosomal instability and aneuploidy in cancer. 针对癌症中的染色体不稳定性和非整倍体。
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-03-01 Epub Date: 2024-02-13 DOI: 10.1016/j.tips.2024.01.009
Sugandha Bhatia, Kum Kum Khanna, Pascal H G Duijf
{"title":"Targeting chromosomal instability and aneuploidy in cancer.","authors":"Sugandha Bhatia, Kum Kum Khanna, Pascal H G Duijf","doi":"10.1016/j.tips.2024.01.009","DOIUrl":"10.1016/j.tips.2024.01.009","url":null,"abstract":"<p><p>Cancer development and therapy resistance are driven by chromosomal instability (CIN), which causes chromosome gains and losses (i.e., aneuploidy) and structural chromosomal alterations. Technical limitations and knowledge gaps have delayed therapeutic targeting of CIN and aneuploidy in cancers. However, our toolbox for creating and studying aneuploidy in cell models has greatly expanded recently. Moreover, accumulating evidence suggests that seven conventional antimitotic chemotherapeutic drugs achieve clinical response by inducing CIN instead of mitotic arrest, although additional anticancer activities may also contribute in vivo. In this review, we discuss these recent developments. We also highlight new discoveries, which together show that 25 chromosome arm aneuploidies (CAAs) may be targetable by 36 drugs across 14 types of cancer. Collectively, these advances offer many new opportunities to improve cancer treatment.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736207","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
Advances in inhibitor development targeting the PWWP domain. 针对 PWWP 结构域的抑制剂开发进展。
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-03-01 Epub Date: 2024-02-09 DOI: 10.1016/j.tips.2024.01.007
Yunyuan Huang, Yanxi Li, Jinrong Min
{"title":"Advances in inhibitor development targeting the PWWP domain.","authors":"Yunyuan Huang, Yanxi Li, Jinrong Min","doi":"10.1016/j.tips.2024.01.007","DOIUrl":"10.1016/j.tips.2024.01.007","url":null,"abstract":"<p><p>The PWWP domain binds to both histone and DNA of a nucleosome in a bivalent way. PWWP domain-containing proteins are involved in different biological processes, and their aberrant expression is implicated in various human diseases. Here, we discuss the recent developments and challenges in targeting the PWWP domain for therapeutic intervention.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716435","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
Histone lysine acetyltransferase inhibitors: an emerging class of drugs for cancer therapy 组蛋白赖氨酸乙酰转移酶抑制剂：一类新兴的癌症治疗药物
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-02-20 DOI: 10.1016/j.tips.2024.01.010
Jeffrey White, Frederick A. Derheimer, Kristen Jensen-Pergakes, Shawn O’Connell, Shikhar Sharma, Noah Spiegel, Thomas A. Paul
{"title":"Histone lysine acetyltransferase inhibitors: an emerging class of drugs for cancer therapy","authors":"Jeffrey White, Frederick A. Derheimer, Kristen Jensen-Pergakes, Shawn O’Connell, Shikhar Sharma, Noah Spiegel, Thomas A. Paul","doi":"10.1016/j.tips.2024.01.010","DOIUrl":"https://doi.org/10.1016/j.tips.2024.01.010","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139926804","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
Leveraging spatial omics for the development of precision sarcoma treatments. 利用空间全息技术开发肉瘤精准治疗方法。
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-02-01 Epub Date: 2024-01-11 DOI: 10.1016/j.tips.2023.12.006
Cui Tu, Arutha Kulasinghe, Andrew Barbour, Fernando Souza-Fonseca-Guimaraes
{"title":"Leveraging spatial omics for the development of precision sarcoma treatments.","authors":"Cui Tu, Arutha Kulasinghe, Andrew Barbour, Fernando Souza-Fonseca-Guimaraes","doi":"10.1016/j.tips.2023.12.006","DOIUrl":"10.1016/j.tips.2023.12.006","url":null,"abstract":"<p><p>Sarcomas are rare and heterogeneous cancers that arise from bone or soft tissue, and are the second most prevalent solid cancer in children and adolescents. Owing to the complex nature of pediatric sarcomas, the development of therapeutics for pediatric sarcoma has seen little progress in the past decades. Existing treatments are largely limited to chemotherapy, radiation, and surgery. Limited knowledge of the sarcoma tumor microenvironment (TME) and of well-defined target antigens in the different subtypes necessitates an alternative investigative approach to improve treatments. Recent advances in spatial omics technologies have enabled a more comprehensive study of the TME in multiple cancers. In this opinion article we discuss advances in our understanding of the TME of some cancers enabled by spatial omics technologies, and we explore how these technologies might advance the development of precision treatments for sarcoma, especially pediatric sarcoma.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139425597","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
Context-dependent role of SIRT3 in cancer. SIRT3 在癌症中的作用与环境有关。
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-02-01 Epub Date: 2024-01-19 DOI: 10.1016/j.tips.2023.12.005
Jin Zhang, Jing Ye, Shiou Zhu, Bo Han, Bo Liu
{"title":"Context-dependent role of SIRT3 in cancer.","authors":"Jin Zhang, Jing Ye, Shiou Zhu, Bo Han, Bo Liu","doi":"10.1016/j.tips.2023.12.005","DOIUrl":"10.1016/j.tips.2023.12.005","url":null,"abstract":"<p><p>Sirtuin 3 (SIRT3), an NAD<sup>+</sup>-dependent deacetylase, plays a key role in the modulation of metabolic reprogramming and regulation of cell death, as well as in shaping tumor phenotypes. Owing to its critical role in determining tumor-type specificity or the direction of tumor evolution, the development of small-molecule modulators of SIRT3, including inhibitors and activators, is of significant interest. In this review, we discuss recent studies on the oncogenic or tumor-suppressive functions of SIRT3, evaluate advances in SIRT3-targeted drug discovery, and present potential avenues for the design of small-molecule modulators of SIRT3 for cancer therapy.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139502798","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
Emerging epigenetic insights into aging mechanisms and interventions. 表观遗传学对衰老机制和干预措施的新见解。
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-02-01 Epub Date: 2024-01-11 DOI: 10.1016/j.tips.2023.12.002
Zeming Wu, Weiqi Zhang, Jing Qu, Guang-Hui Liu
{"title":"Emerging epigenetic insights into aging mechanisms and interventions.","authors":"Zeming Wu, Weiqi Zhang, Jing Qu, Guang-Hui Liu","doi":"10.1016/j.tips.2023.12.002","DOIUrl":"10.1016/j.tips.2023.12.002","url":null,"abstract":"<p><p>Epigenetic dysregulation emerges as a critical hallmark and driving force of aging. Although still an evolving field with much to explore, it has rapidly gained significance by providing valuable insights into the mechanisms of aging and potential therapeutic opportunities for age-related diseases. Recent years have witnessed remarkable strides in our understanding of the epigenetic landscape of aging, encompassing pivotal elements, such as DNA methylation, histone modifications, RNA modifications, and noncoding (nc) RNAs. Here, we review the latest discoveries that shed light on new epigenetic mechanisms and critical targets for predicting and intervening in aging and related disorders. Furthermore, we explore burgeoning interventions and exemplary clinical trials explicitly designed to foster healthy aging, while contemplating the potential ramifications of epigenetic influences.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139432861","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
Subscription and Copyright Information 订阅和版权信息
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-02-01 DOI: 10.1016/s0165-6147(24)00011-7
{"title":"Subscription and Copyright Information","authors":"","doi":"10.1016/s0165-6147(24)00011-7","DOIUrl":"https://doi.org/10.1016/s0165-6147(24)00011-7","url":null,"abstract":"Abstract not available","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139656382","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
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