烟酰胺腺嘌呤二核苷酸为基础的治疗和更新

Title:Nicotinamide Adenine Dinucleotide Based Therapeutics, Update

Volume: 22 Issue: 34

Author(s): K.W. Pankiewicz, R. Petrelli, R. Singh and K. Felczak

Affiliation:

关键词: NAD类似物，NAD依赖酶，IMP脱氢酶，NAD激酶，细菌连接酶，NMN腺苷转移酶，磷酸核糖转移酶，酶抑制剂，药物设计

摘要: About 500 NAD (P)-dependent enzymes in the cell use NAD (P) as a cofactor or a substrate. This family of broadly diversified enzymes is crucial for maintaining homeostasis of all living organisms. The NAD binding domain of these enzymes is conserved and it was believed that NAD mimics would not be of therapeutic value due to lack of selectivity. Consequently, only mycophenolic acid which selectively binds at the cofactor pocket of NAD-dependent IMP-dehydrogenase (IMPDH) has been approved as an immunosuppressant. Recently, it became clear that the NAD (P)-binding domain was structurally much more diversified than anticipated and numerous highly potent and selective inhibitors of NAD (P) dependent enzymes have been reported. It is likely, that as in the case of protein kinases inhibitors, inhibitors of NAD (P)-dependent enzymes would find soon their way to the clinic. In this review, recent developments of selective inhibitors of NAD-dependent human IMPDH, as well as inhibitors of IMPDHs from parasites, and from bacterial sources are reported. Therapies against Cryptosporidium parvum and the development of new antibiotics that are on the horizon will be discussed. New inhibitors of bacterial NAD-ligases, NAD-kinases, NMN-adenylyl transferases, as well as phosphoribosyl transferases are also described. Although none of these compounds has yet to be approved, the progress in revealing and understanding crucial factors that might allow for designing more potent and efficient drug candidates is enormous and highly encouraging.

Cite this article as:

K.W. Pankiewicz, R. Petrelli, R. Singh and K. Felczak , Nicotinamide Adenine Dinucleotide Based Therapeutics, Update, Current Medicinal Chemistry 2015; 22 (34) . https://dx.doi.org/10.2174/0929867322666150821100720