Gao Yongzhi, Martin Nathaniel I, van Haren Matthijs J
Biological Chemistry Group, Institute of Biology Leiden, Leiden University, Sylviusweg 72, 2333 BE Leiden, the Netherlands.
Biological Chemistry Group, Institute of Biology Leiden, Leiden University, Sylviusweg 72, 2333 BE Leiden, the Netherlands.
Drug Discov Today. 2021 Nov;26(11):2699-2706. doi: 10.1016/j.drudis.2021.05.011. Epub 2021 May 21.
Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (NA) to generate 1-methyl nicotinamide. Since its discovery 70 years ago, the appreciation of the role of NNMT in human health has evolved from serving only metabolic functions to also being a driving force in diseases, including a variety of cancers. Despite the increasing evidence indicating NNMT as a viable therapeutic target, the development of cell-active inhibitors against this enzyme is lacking. In this review, we provide an overview of the current status of NNMT inhibitor development, relevant in vitro and in vivo studies, and a discussion of the challenges faced in the development of NNMT inhibitors.
烟酰胺N-甲基转移酶(NNMT)将烟酰胺(NA)甲基化生成1-甲基烟酰胺。自70年前被发现以来,人们对NNMT在人类健康中作用的认识已从仅发挥代谢功能演变为也是包括多种癌症在内的疾病的驱动因素。尽管越来越多的证据表明NNMT是一个可行的治疗靶点,但针对该酶的细胞活性抑制剂的开发仍很缺乏。在这篇综述中,我们概述了NNMT抑制剂开发的现状、相关的体外和体内研究,并讨论了NNMT抑制剂开发中面临的挑战。