2. Academic Validation
  3. Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 inhibitors: Research progress and prospects

Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 inhibitors: Research progress and prospects

  • Eur J Med Chem. 2024 Mar 5:267:116211. doi: 10.1016/j.ejmech.2024.116211.
Dezhong Guan 1,  Lincheng Fang 2,  Mingshun Feng 3,  Shi Guo 4,  Lingfeng Xie 4,  Chao Chen 4,  Xue Sun 1,  Qingyun Wu 4,  Xinrui Yuan 4,  Zuoquan Xie 5,  Jinpei Zhou 6,  Huibin Zhang 7
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, China Pharmaceutical University, TongjiaXiang 24, 210009, Nanjing, China.
  • 2 Peking University Shenzhen Graduate School, Shenzhen, China.
  • 3 Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • 4 Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
  • 5 Division of Antitumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Electronic address: [email protected].
  • 6 Department of Medicinal Chemistry, China Pharmaceutical University, TongjiaXiang 24, 210009, Nanjing, China. Electronic address: [email protected].
  • 7 Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China. Electronic address: [email protected].
PMID: 38359537 DOI: 10.1016/j.ejmech.2024.116211
Abstract

The Cancer immunotherapies involved in cGAS-STING pathway have been made great progress in recent years. STING agonists exhibit broad-spectrum anti-tumor effects with strong immune response. As a negative regulator of the cGAS-STING pathway, ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) can hydrolyze extracellular 2', 3'-cGAMP and reduce extracellular 2', 3'-cGAMP concentration. ENPP1 has been validated to play important roles in diabetes, cancers, and Cardiovascular Disease and now become a promising target for tumor immunotherapy. Several ENPP1 inhibitors under development have shown good anti-tumor effects alone or in combination with Other agents in clinical and preclinical researches. In this review, the biological profiles of ENPP1 were described, and the structures and the structure-activity relationships (SAR) of the known ENPP1 inhibitors were summarized. This review also provided the prospects and challenges in the development of ENPP1 inhibitors.

Keywords

2′,3′-cGAMP; ENPP1 inhibitors; Tumor immunotherapy; cGAS-STING pathway.

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