{"title":"用于乳腺癌治疗的 PI3K 抑制剂的研究进展和开发策略:综述(2016 年至今)。","authors":"Rujue Peng, Yujie Zhan, Anqi Li, Qiaoli Lv, Shan Xu","doi":"10.1016/j.bioorg.2024.107934","DOIUrl":null,"url":null,"abstract":"<p><p>Phosphatidylinositol 3-kinases (PI3Ks) are widely expressed in tissues and cells throughout the body and are involved in a variety of physiological processes including cell growth and metabolism. The phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of the rapamycin (mTOR) signaling pathway (PI3K/AKT/mTOR, PAM) is a promising target for the treatment of many cancer types because it is significantly linked to tumorigenesis and development. Aberrant activation of this pathway is observed in the majority of tumors, particularly in breast cancer. The development of PI3K inhibitors has received much attention in recent years. PI3K inhibitors are effective drugs for the treatment of various types of malignant tumors. The FDA has approved a few PI3K inhibitors for commercialization, and the majority of PI3K inhibitors under clinical trials are expected to conquer cancers, including breast cancer. This article discusses the link between the PAM signaling system and breast cancer, as well as the current clinical applications of PAM pathway inhibitors in the treatment of breast cancer. This work summarizes and describes the development tactics of seven types of PI3K inhibitors targeting breast cancer, including morpholine-substituted thienopyrimidines, with the goal of informing future PI3K inhibitor research.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107934"},"PeriodicalIF":4.5000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Research progress and development strategy of PI3K inhibitors for breast cancer treatment: A review (2016-present).\",\"authors\":\"Rujue Peng, Yujie Zhan, Anqi Li, Qiaoli Lv, Shan Xu\",\"doi\":\"10.1016/j.bioorg.2024.107934\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Phosphatidylinositol 3-kinases (PI3Ks) are widely expressed in tissues and cells throughout the body and are involved in a variety of physiological processes including cell growth and metabolism. The phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of the rapamycin (mTOR) signaling pathway (PI3K/AKT/mTOR, PAM) is a promising target for the treatment of many cancer types because it is significantly linked to tumorigenesis and development. Aberrant activation of this pathway is observed in the majority of tumors, particularly in breast cancer. The development of PI3K inhibitors has received much attention in recent years. PI3K inhibitors are effective drugs for the treatment of various types of malignant tumors. The FDA has approved a few PI3K inhibitors for commercialization, and the majority of PI3K inhibitors under clinical trials are expected to conquer cancers, including breast cancer. This article discusses the link between the PAM signaling system and breast cancer, as well as the current clinical applications of PAM pathway inhibitors in the treatment of breast cancer. This work summarizes and describes the development tactics of seven types of PI3K inhibitors targeting breast cancer, including morpholine-substituted thienopyrimidines, with the goal of informing future PI3K inhibitor research.</p>\",\"PeriodicalId\":257,\"journal\":{\"name\":\"Bioorganic Chemistry\",\"volume\":\"153 \",\"pages\":\"107934\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioorganic Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1016/j.bioorg.2024.107934\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/28 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1016/j.bioorg.2024.107934","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/28 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Research progress and development strategy of PI3K inhibitors for breast cancer treatment: A review (2016-present).
Phosphatidylinositol 3-kinases (PI3Ks) are widely expressed in tissues and cells throughout the body and are involved in a variety of physiological processes including cell growth and metabolism. The phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of the rapamycin (mTOR) signaling pathway (PI3K/AKT/mTOR, PAM) is a promising target for the treatment of many cancer types because it is significantly linked to tumorigenesis and development. Aberrant activation of this pathway is observed in the majority of tumors, particularly in breast cancer. The development of PI3K inhibitors has received much attention in recent years. PI3K inhibitors are effective drugs for the treatment of various types of malignant tumors. The FDA has approved a few PI3K inhibitors for commercialization, and the majority of PI3K inhibitors under clinical trials are expected to conquer cancers, including breast cancer. This article discusses the link between the PAM signaling system and breast cancer, as well as the current clinical applications of PAM pathway inhibitors in the treatment of breast cancer. This work summarizes and describes the development tactics of seven types of PI3K inhibitors targeting breast cancer, including morpholine-substituted thienopyrimidines, with the goal of informing future PI3K inhibitor research.
期刊介绍:
Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry.
For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature.
The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.