Baetz Kristin, McHardy Lianne, Gable Ken, Tarling Tamsin, Rebérioux Delphine, Bryan Jenny, Andersen Raymond J, Dunn Teresa, Hieter Phil, Roberge Michel
Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada V5Z 4H4.
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4525-30. doi: 10.1073/pnas.0307122101. Epub 2004 Mar 15.
Methods to systematically test drugs against all possible proteins in a cell are needed to identify the targets underlying their therapeutic action and unwanted effects. Here, we show that a genome-wide drug-induced haploinsufficiency screen by using yeast can reveal drug mode of action in yeast and can be used to predict drug mode of action in human cells. We demonstrate that dihydromotuporamine C, a compound in preclinical development that inhibits angiogenesis and metastasis by an unknown mechanism, targets sphingolipid metabolism. The systematic, unbiased and genome-wide nature of this technique makes it attractive as a general approach to identify cellular pathways affected by drugs.
需要系统地测试药物针对细胞中所有可能蛋白质的方法，以确定其治疗作用和不良影响背后的靶点。在这里，我们表明，通过酵母进行全基因组药物诱导的单倍体不足筛选，可以揭示酵母中的药物作用模式，并可用于预测人类细胞中的药物作用模式。我们证明，二氢莫土波明C是一种处于临床前开发阶段的化合物，通过未知机制抑制血管生成和转移，其靶点是鞘脂代谢。该技术的系统性、无偏性和全基因组性质使其成为一种识别受药物影响的细胞途径的通用方法，颇具吸引力。
