2. Academic Validation
  3. Design, synthesis and SAR studies of NAD analogues as potent inhibitors towards CD38 NADase

Design, synthesis and SAR studies of NAD analogues as potent inhibitors towards CD38 NADase

  • Molecules. 2014 Sep 29;19(10):15754-67. doi: 10.3390/molecules191015754.
Shengjun Wang 1,  Wenjie Zhu 2,  Xuan Wang 3,  Jianguo Li 4,  Kehui Zhang 5,  Liangren Zhang 6,  Yong-Juan Zhao 7,  Hon Cheung Lee 8,  Lihe Zhang 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. [email protected].
  • 2 School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518052, China. [email protected].
  • 3 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. [email protected].
  • 4 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. [email protected].
  • 5 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. [email protected].
  • 6 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. [email protected].
  • 7 School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518052, China. [email protected].
  • 8 School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518052, China. [email protected].
  • 9 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. [email protected].
PMID: 25268725 DOI: 10.3390/molecules191015754
Abstract

Nicotinamide adenine dinucleotide (NAD), one of the most important coenzymes in the cells, is a substrate of the signaling Enzyme CD38, by which NAD is converted to a second messenger, cyclic ADP-ribose, which releases calcium from intracellular calcium stores. Starting with 2'-deoxy-2'-fluoroarabinosyl-β-nicotinamide adenine dinucleotide (ara-F NAD), a series of NAD analogues were synthesized and their activities to inhibit CD38 NAD glycohydrolase (NADase) were evaluated. The adenosine-modified analogues showed potent inhibitory activities, among which 2'-deoxy-2'-fluoroarabinosyl-β-nicotinamide guanine dinucleotide (ara-F NGD) was the most effective one. The structure-activity relationship of NAD analogues was also discussed.

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