Discovery of natural product ellagic acid as a potent CD73 and CD39 dual inhibitor

  • Bioorg Med Chem Lett. 2021 Feb 15:34:127758. doi: 10.1016/j.bmcl.2020.127758.
Yuan Wang  1 ,  Chuanhao Wang  2 ,  Yazhao Zhu  2 ,  Yanming Zhang  3 ,  Baobao Chen  2 ,  Yuelin Wu  4 ,  Jianzhong Yao  5 ,  Zhenyuan Miao  6
Affiliations
  • 1. School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, People's Republic of China.
  • 2. School of Chemical and Environmental Engineering, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai 201418, People's Republic of China.
  • 3. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
  • 4. School of Chemical and Environmental Engineering, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai 201418, People's Republic of China. Electronic address: [email protected].
  • 5. School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, People's Republic of China; School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: [email protected].
  • 6. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: [email protected].
PMID: 33359608 DOI: 10.1016/j.bmcl.2020.127758
Abstract

The ATP-adenosine pathway has been recently identified as an attractive immune-oncology target and several drug candidates have been entered clinic trials. Inspired by the report of the first small-molecule CD73inhibitor AB680, we describe the discovery of natural product ellagic acid as a dual CD73 and CD39 inhibitor with an IC50 value of 1.85 ± 0.21 μM and 0.50 ± 0.22 μM, respectively. The result of cytotoxicity assays indicated that ellagic acid is a valuable lead compound with low cytotoxicity effect for immune therapy.

Keywords
CD73 inhibitors; Drug design; Ellagic acid; Immunosuppression.