Acta materia medica最新文献_第8页

PROTAC Degraders with Ligands Recruiting MDM2 E3 Ubiquitin Ligase: An Updated Perspective. 与配体招募MDM2 E3泛素连接酶的PROTAC降解物:一个最新的观点。

Acta materia medica Pub Date : 2022-01-01 DOI: 10.15212/amm-2022-0010

Xin Han, Wenyi Wei, Yi Sun

{"title":"PROTAC Degraders with Ligands Recruiting MDM2 E3 Ubiquitin Ligase: An Updated Perspective.","authors":"Xin Han, Wenyi Wei, Yi Sun","doi":"10.15212/amm-2022-0010","DOIUrl":"https://doi.org/10.15212/amm-2022-0010","url":null,"abstract":"Mouse double minute 2 (MDM2) is an E3 ubiquitin ligase which effectively degrades tumor suppressor p53. In the past two decades, many MDM2 inhibitors that disrupt the MDM2-p53 binding have been discovered and developed. Given that the MDM2-p53 forms auto-regulatory loop in which p53 is a substrate of MDM2 for targeted degradation, while MDM2 is a p53 target for transcriptional upregulation, these MDM2 inhibitors have limited efficacy due to p53 degradation by accumulated MDM2 upon rapid in vivo clearance of the MDM2 inhibitors. Fortunately, proteolysis targeting chimeras (PROTACs), a novel therapeutic strategy, overcome the limitations of MDM2 inhibitors. Some of MDM2 inhibitors developed in the past two decades have been used in PROTAC technology for two applications: 1) as component 1 to bind with endogenous MDM2 as a target for PROTAC-based degradation of MDM2; and 2) as component 2 to bind with endogenous MDM2 as a PROTAC E3 ligand for PROTAC-based degradation of other oncogenic proteins. In this review, we summarize current progress in the discovery and development of MDM2-based PROTAC drugs with future perspectives and challenges for their applications in effective treatment of human cancer.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"1 2","pages":"244-259"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9211018/pdf/nihms-1812315.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9628419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 16

The 'New (Nu)-clear' evidence for the tumor-driving role of PI3K. PI3K 推动肿瘤作用的 "新（Nu）-明确 "证据。

Acta materia medica Pub Date : 2022-01-01 Epub Date: 2022-05-16 DOI: 10.15212/amm-2022-0013

Franklin Mayca Pozo, Tony Hunter, Youwei Zhang

{"title":"The 'New (Nu)-clear' evidence for the tumor-driving role of PI3K.","authors":"Franklin Mayca Pozo, Tony Hunter, Youwei Zhang","doi":"10.15212/amm-2022-0013","DOIUrl":"10.15212/amm-2022-0013","url":null,"abstract":"The classical phosphatidylinositol 3-kinases (PI3Ks) are heterodimers of p110 and p85. PIK3CA, the gene encoding the catalytic p110α subunit, is one of the most frequently mutated oncogenes in human cancers with hot spot mutations occurring in the helical domain or in the kinase domain. Tumors with these two types of PIK3CA mutations show overlapping yet distinct phenotypes; however, the underlying mechanisms remain unclear. In a recent publication [1], Hao et al revealed exciting findings about the PI3K p85β regulatory subunit in promoting PIK3CA helical domain mutation-driven cancer progression. The authors found that p85β disassociated from the PI3K complex and translocated into the nucleus only in cancer cells harboring PIK3CA helical domain mutations. Disrupting nuclear localization of p85β suppressed mouse tumor growth of cancer cells with PIK3CA helical domain mutation. Mechanistically, they elegantly showed that nuclear p85β recruited the deubiquitinase USP7 to stabilize the histone methyltransferases EZH1/2, leading to enhanced H3K27 trimethylation and gene transcription. Combining an EZH inhibitor with a PI3K inhibitor specifically resulted in regression of mouse xenograft tumors with PIK3CA helical domain mutations. These findings illustrate a previously uncharacterized function of p85β in tumor development and suggest an effective approach to target tumors with PIK3CA helical mutations.","PeriodicalId":72055,"journal":{"name":"Acta materia medica","volume":"1 2","pages":"193-196"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10191166/pdf/nihms-1849224.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9496355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cytotoxic compounds from marine actinomycetes: Sources, Structures and Bioactivity. 海洋放线菌的细胞毒性化合物:来源、结构和生物活性。

Acta materia medica Pub Date : 2022-01-01 DOI: 10.15212/amm-2022-0028

Ziyan Qiu, Yinshuang Wu, Kunyan Lan, Shiyi Wang, Huilin Yu, Yufei Wang, Cong Wang, Shugeng Cao

引用次数: 2

Drug discovery is an eternal challenge for the biomedical sciences 药物发现是生物医学科学的永恒挑战

Acta materia medica Pub Date : 2022-01-01 DOI: 10.15212/amm-2022-1001

L. Hua, Wei Wenyi, Hongxi Xu

引用次数: 55