{"title":"代谢途径通量信息在抗癌药物设计中的应用。","authors":"L G Boros, T F Boros","doi":"10.1007/2789_2008_094","DOIUrl":null,"url":null,"abstract":"<p><p>The metabolic phenotype of tumor cells promote the proliferative state, which indicates that (a) cell transformation is associated with the activation of specific metabolic substrate channels toward nucleic acid synthesis and (b) increased expression phosphorylation, allosteric or transcriptional regulation of intermediary metabolic enzymes and their substrate availability together mediate unlimited growth. It is evident that cell transformation due to various K-ras point mutations is associated with the activation of specific metabolic substrate channels that increase glucose channeling toward nucleic acid synthesis. Therefore, phosphorylation, allosteric and transcriptional regulation of intermediary metabolic enzymes and their substrate availability together mediate cell transformation and growth. In this review, we summarize opposite changes in metabolic phenotypes induced by various cell-transforming agents, and tumor growth-inhibiting drugs or phytochemicals, or novel synthetic antileukemic drugs such as imatinib mesylate (Gleevec). Metabolic enzymes that further incite growth signaling pathways and thus promote malignant cell transformation serve as high-efficacy nongenetic novel targets for cancer therapies.</p>","PeriodicalId":87471,"journal":{"name":"Ernst Schering Foundation symposium proceedings","volume":" 4","pages":"189-203"},"PeriodicalIF":0.0000,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/2789_2008_094","citationCount":"8","resultStr":"{\"title\":\"Use of metabolic pathway flux information in anticancer drug design.\",\"authors\":\"L G Boros, T F Boros\",\"doi\":\"10.1007/2789_2008_094\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The metabolic phenotype of tumor cells promote the proliferative state, which indicates that (a) cell transformation is associated with the activation of specific metabolic substrate channels toward nucleic acid synthesis and (b) increased expression phosphorylation, allosteric or transcriptional regulation of intermediary metabolic enzymes and their substrate availability together mediate unlimited growth. It is evident that cell transformation due to various K-ras point mutations is associated with the activation of specific metabolic substrate channels that increase glucose channeling toward nucleic acid synthesis. Therefore, phosphorylation, allosteric and transcriptional regulation of intermediary metabolic enzymes and their substrate availability together mediate cell transformation and growth. In this review, we summarize opposite changes in metabolic phenotypes induced by various cell-transforming agents, and tumor growth-inhibiting drugs or phytochemicals, or novel synthetic antileukemic drugs such as imatinib mesylate (Gleevec). Metabolic enzymes that further incite growth signaling pathways and thus promote malignant cell transformation serve as high-efficacy nongenetic novel targets for cancer therapies.</p>\",\"PeriodicalId\":87471,\"journal\":{\"name\":\"Ernst Schering Foundation symposium proceedings\",\"volume\":\" 4\",\"pages\":\"189-203\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2007-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1007/2789_2008_094\",\"citationCount\":\"8\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Ernst Schering Foundation symposium proceedings\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1007/2789_2008_094\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ernst Schering Foundation symposium proceedings","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/2789_2008_094","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Use of metabolic pathway flux information in anticancer drug design.
The metabolic phenotype of tumor cells promote the proliferative state, which indicates that (a) cell transformation is associated with the activation of specific metabolic substrate channels toward nucleic acid synthesis and (b) increased expression phosphorylation, allosteric or transcriptional regulation of intermediary metabolic enzymes and their substrate availability together mediate unlimited growth. It is evident that cell transformation due to various K-ras point mutations is associated with the activation of specific metabolic substrate channels that increase glucose channeling toward nucleic acid synthesis. Therefore, phosphorylation, allosteric and transcriptional regulation of intermediary metabolic enzymes and their substrate availability together mediate cell transformation and growth. In this review, we summarize opposite changes in metabolic phenotypes induced by various cell-transforming agents, and tumor growth-inhibiting drugs or phytochemicals, or novel synthetic antileukemic drugs such as imatinib mesylate (Gleevec). Metabolic enzymes that further incite growth signaling pathways and thus promote malignant cell transformation serve as high-efficacy nongenetic novel targets for cancer therapies.