{"title":"从药物化学角度评估人类运动基因组的黑暗程度","authors":"Selina Voßen, Elena Xerxa, Jürgen Bajorath","doi":"10.1021/acs.jmedchem.4c01992","DOIUrl":null,"url":null,"abstract":"In drug discovery, human protein kinases (PKs) represent one of the major target classes due to their central role in cellular signaling, implication in various diseases as a consequence of deregulated signaling, and notable druggability. Individual PKs and their disease biology have been explored to different degrees, giving rise to heterogeneous functional knowledge and disease associations across the human kinome. The U.S. National Institutes of Health previously designated 162 understudied (“dark”) human PKs and lipid kinases due to the lack of functional annotations and high-quality molecular probes for functional investigations. Given the large volumes of available PK inhibitors (PKIs) and activity data, we have systematically analyzed the distribution of PKIs and associated data at different confidence levels across the human kinome and distinguished between chemically explored, underexplored, and unexplored PKs. The analysis provides a medicinal chemistry-centric view of PK exploration and further extends prior assessment of the dark kinome.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":6.8000,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Assessing Darkness of the Human Kinome from a Medicinal Chemistry Perspective\",\"authors\":\"Selina Voßen, Elena Xerxa, Jürgen Bajorath\",\"doi\":\"10.1021/acs.jmedchem.4c01992\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"In drug discovery, human protein kinases (PKs) represent one of the major target classes due to their central role in cellular signaling, implication in various diseases as a consequence of deregulated signaling, and notable druggability. Individual PKs and their disease biology have been explored to different degrees, giving rise to heterogeneous functional knowledge and disease associations across the human kinome. The U.S. National Institutes of Health previously designated 162 understudied (“dark”) human PKs and lipid kinases due to the lack of functional annotations and high-quality molecular probes for functional investigations. Given the large volumes of available PK inhibitors (PKIs) and activity data, we have systematically analyzed the distribution of PKIs and associated data at different confidence levels across the human kinome and distinguished between chemically explored, underexplored, and unexplored PKs. The analysis provides a medicinal chemistry-centric view of PK exploration and further extends prior assessment of the dark kinome.\",\"PeriodicalId\":46,\"journal\":{\"name\":\"Journal of Medicinal Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2024-09-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Medicinal Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.jmedchem.4c01992\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acs.jmedchem.4c01992","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Assessing Darkness of the Human Kinome from a Medicinal Chemistry Perspective
In drug discovery, human protein kinases (PKs) represent one of the major target classes due to their central role in cellular signaling, implication in various diseases as a consequence of deregulated signaling, and notable druggability. Individual PKs and their disease biology have been explored to different degrees, giving rise to heterogeneous functional knowledge and disease associations across the human kinome. The U.S. National Institutes of Health previously designated 162 understudied (“dark”) human PKs and lipid kinases due to the lack of functional annotations and high-quality molecular probes for functional investigations. Given the large volumes of available PK inhibitors (PKIs) and activity data, we have systematically analyzed the distribution of PKIs and associated data at different confidence levels across the human kinome and distinguished between chemically explored, underexplored, and unexplored PKs. The analysis provides a medicinal chemistry-centric view of PK exploration and further extends prior assessment of the dark kinome.
期刊介绍:
The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents.
The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.