Medicines Research Centre, GlaxoSmithKline, Stevenage, UK.
Clin Pharmacol Ther. 2013 Mar;93(3):263-6. doi: 10.1038/clpt.2012.240. Epub 2012 Dec 11.
Many drug targets are intracellular. To access them, a drug molecule must pass through the cell membrane, a process often facilitated or impeded by transporters. Once in the cytoplasm, basic molecules may become concentrated in organelles. To predict the pharmacologic effect accurately, there must be data concerning the concentration at the target, which is difficult to measure. Techniques that combine mass spectrometry and imaging techniques (matrix-assisted laser desorption/ionization, secondary ion mass spectrometry (SIMS), and nanoSIMS) have promise in addressing this problem.
许多药物靶点是细胞内的。为了接近这些靶点,药物分子必须穿过细胞膜,这一过程通常会受到转运蛋白的促进或阻碍。一旦进入细胞质,基本分子可能会在细胞器中浓缩。为了准确预测药物的作用,必须有关于靶点处浓度的相关数据,而这是很难测量的。结合质谱和成像技术(基质辅助激光解吸/电离、二次离子质谱(SIMS)和纳米 SIMS)的技术有望解决这个问题。