J Biomed Inform - Drug target identification in sphingolipid metabolism by computational systems biology tools: metabolic control analysis and metabolic pathway analysis.

Tópicos

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{ detect(2391) sensit(1101) algorithm(908) }

Resumo

Sphingolipids regulate cellular processes that are critically important in cell's fate and function in cancer development and progression. This fact underlies the basics of the novel cancer therapy approach. The pharmacological manipulation of the sphingolipid metabolism in cancer therapeutics necessitates the detailed understanding of the pathway. Two computational systems biology tools are used to identify potential drug target enzymes among sphingolipid pathway that can be further utilized in drug design studies for cancer therapy. The enzymes in sphingolipid pathway were ranked according to their roles in controlling the metabolic network by metabolic control analysis. The physiologically connected reactions, i.e. biologically significant and functional modules of network, were identified by metabolic pathway analysis. The final set of candidate drug target enzymes are selected such that their manipulation leads to ceramide accumulation and long chain base phosphates depletion. The mathematical tools' efficiency for drug target identification performed in this study is validated by clinically available drugs.

Resumo Limpo

sphingolipid regul cellular process critic import cell fate function cancer develop progress fact under basic novel cancer therapi approach pharmacolog manipul sphingolipid metabol cancer therapeut necessit detail understand pathway two comput system biolog tool use identifi potenti drug target enzym among sphingolipid pathway can util drug design studi cancer therapi enzym sphingolipid pathway rank accord role control metabol network metabol control analysi physiolog connect reaction ie biolog signific function modul network identifi metabol pathway analysi final set candid drug target enzym select manipul lead ceramid accumul long chain base phosphat deplet mathemat tool effici drug target identif perform studi valid clinic avail drug

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