Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Malaga, 29071, Malaga, Spain.
Curr Pharm Des. 2014;20(2):293-300. doi: 10.2174/13816128113199990030.
It has been estimated that the cost of bringing a new drug onto the market is 10 years and 0.5-2 billions of dollars, making it a non-profitable project, particularly in the case of low prevalence diseases. The advances in Systems Biology have been absolutely decisive for drug discovery, as iterative rounds of predictions made from in silico models followed by selected experimental validations have resulted in a substantial saving of time and investments. Many diseases have their origins in proteins that are not located in the cytosol but in intracellular compartments (i.e. mitochondria, lysosome, peroxisome and others) or cell membranes. In these cases, biocomputational approaches present limitations to their study. In the present work, we review them and propose new initiatives to advance towards a safer, more efficient and personalized pharmacology. This focus could be especially useful for drug discovery and the reposition of known drugs in rare and emergent diseases associated with compartmentalized proteins.
据估计，将一种新药推向市场需要 10 年时间和 0.5-20 亿美元的成本，因此对于发病率较低的疾病来说，这是一个无利可图的项目。系统生物学的进步对药物发现绝对具有决定性意义，因为从计算机模型中进行迭代预测，然后进行选定的实验验证，已经大大节省了时间和投资。许多疾病的起源是位于细胞溶质以外的蛋白质，例如在内质网、溶酶体、过氧化物酶体和其他细胞器或细胞膜中。在这些情况下，生物计算方法对其研究存在局限性。在本工作中，我们对它们进行了回顾，并提出了新的倡议，以推进更安全、更有效和个性化的药理学。这种方法对于发现药物和重新定位与分隔蛋白相关的罕见和突发疾病的已知药物可能特别有用。
