Journal of Chinese Pharmaceutical Sciences ›› 2015, Vol. 24 ›› Issue (8): 514-523.DOI: 10.5246/jcps.2015.08.065

• Original articles • Previous Articles     Next Articles

Investigation of the effect of 2'-substitution of NMN analogues on CD38 NADase inhibitory activity

Jianguo Li1, Fen Pei1, Wenjie Zhu2, Hongwei Jin1*, Yongjuan Zhao2, Liangren Zhang1*, Honcheung Lee2, Lihe Zhang1   

  1. 1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
    2. School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China
  • Received:2015-04-13 Revised:2015-05-11 Online:2015-08-22 Published:2015-05-28
  • Contact: Tel.: 86-10-82802567, Fax: 86-10-82802724, Tel/Fax: 86-10-82805514, E-mail:,
  • Supported by:
    National Natural Sciences Foundation of China (Grant No. 91213302, 81172917 and 31301156).


CD38 is a nicotinamide adenine dinucleotide (NAD)-metabolizing enzyme responsible for catalyzing the synthesis of Ca2+ messengers. Its inhibitor plays an important role in probing the regulatory pathway and physiological function of CD38. For clearly understanding the effect of 2'-substitution of nicotinamide mononucleotide (NMN) analogues on CD38 NADase inhibitory activity, a new kind of NMN analogues with two substituents at C-2' was investigated. Molecular dynamics (MD) simulation and quantum chemical calculation were used to investigate the mechanism by which 2'-substitution affects the inhibitory activity. The results showed that two substituents at C-2' interfered the formation of covalent bond between C-1' of NMN analogues and CD38. The findings of this study will be helpful for comprehensively clarifying the structure-activity relationships of NMN- related CD38 NADase’s inhibitor.

Key words: CD38, NMN analogues, Structure-activity relationship, Molecular modeling

CLC Number: