Röhrig Ute F, Majjigapu Somi Reddy, Vogel Pierre, Zoete Vincent, Michielin Olivier
Molecular Modeling Group, SIB Swiss Institute of Bioinformatics , CH-1015 Lausanne, Switzerland.
Laboratory of Glycochemistry and Asymmetric Synthesis, Ecole Polytechnique Fédérale de Lausanne (EPFL) , CH-1015 Lausanne, Switzerland.
J Med Chem. 2015 Dec 24;58(24):9421-37. doi: 10.1021/acs.jmedchem.5b00326. Epub 2015 May 26.
Since the discovery of indoleamine 2,3-dioxygenase 1 (IDO1) as an attractive target for anticancer therapy in 2003, the search for inhibitors has been intensely pursued both in academia and in pharmaceutical companies. Many novel IDO1 inhibitor scaffolds have been described, and a few potent compounds have entered clinical trials. However, a significant number of the reported compounds contain problematic functional groups, suggesting that enzyme inhibition could be the result of undesirable side reactions instead of selective binding to IDO1. Here, we describe issues in the employed experimental protocols, review and classify reported IDO1 inhibitors, and suggest different approaches for confirming viable inhibitor scaffolds.
自2003年发现吲哚胺2,3-双加氧酶1（IDO1）是抗癌治疗的一个有吸引力的靶点以来，学术界和制药公司都在积极寻找抑制剂。已经描述了许多新型的IDO1抑制剂支架，并且一些强效化合物已进入临床试验。然而，大量报道的化合物含有有问题的官能团，这表明酶抑制可能是不良副反应的结果，而不是与IDO1的选择性结合。在此，我们描述了所采用实验方案中的问题，对报道的IDO1抑制剂进行了综述和分类，并提出了确认可行抑制剂支架的不同方法。
