Horiuchi Kurumi Y
Reaction Biology Corporation, One Great Valley Parkway, Suite 2, Malvern, PA 19355, USA.
Drug Discov Today Technol. 2015 Nov;18:62-8. doi: 10.1016/j.ddtec.2015.10.010. Epub 2015 Nov 21.
The importance of epigenetics in the initiation and progression of disease has attracted many investigators to incorporate this novel and exciting field in drug development. Protein methyltransferases are one of the target classes which have gained attention as potential therapeutic targets after promising results of inhibitors for EZH2 and DOT1L in clinical trials. There are many technologies developed in order to find small molecule inhibitors for protein methyltransferases. However, in contrast to high throughput screening, profiling against different methyltransferases is challenging since each enzyme has a different substrate preference so that it is hard to profile in one assay format. Here, different technologies for methyltransferase assays will be overviewed, and the advantages and disadvantages of each will be discussed.
表观遗传学在疾病发生和发展中的重要性吸引了众多研究人员将这一新颖且令人兴奋的领域纳入药物研发。蛋白质甲基转移酶是一类靶点，在EZH2和DOT1L抑制剂的临床试验取得有前景的结果后，作为潜在治疗靶点受到关注。为了寻找蛋白质甲基转移酶的小分子抑制剂，人们开发了许多技术。然而，与高通量筛选不同，针对不同甲基转移酶进行分析具有挑战性，因为每种酶都有不同的底物偏好，所以很难在一种检测形式中进行分析。在此，将概述甲基转移酶检测的不同技术，并讨论每种技术的优缺点。
