2. Academic Validation
  3. Design, synthesis and pharmacological evaluation of dual PDE3/4 inhibitors for therapy of liver injuries

Design, synthesis and pharmacological evaluation of dual PDE3/4 inhibitors for therapy of liver injuries

  • Eur J Med Chem. 2026 Mar 5:305:118557. doi: 10.1016/j.ejmech.2026.118557.
Gang Li 1,  Xudong Qian 2,  Yan Geng 1,  Jun Wang 2,  Jiaxin Chen 3,  Yanghui Ou 1,  Cheng Chen 1,  Yuchuan Zhong 4,  Wei Pan 2,  Nan Hao 1,  Jiaxin Huang 1,  Guoqin Wu 1,  Qi Zhou 1,  Yali Zhang 1,  Liyan Song 1,  Shuirong Chen 1,  Lianbao Ye 5,  Wen-Hua Chen 6,  Hongliang Yao 7
Affiliations

Affiliations

  • 1 Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China.
  • 2 Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, Guangdong, 529020, China.
  • 3 Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China; School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
  • 4 Zhongshan Torch Development Zone People's Hospital, Zhongshan, Guangdong, 528437, China.
  • 5 School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
  • 6 School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, Guangdong, 529020, China.
  • 7 Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, 510260, China. Electronic address: [email protected].
PMID: 41548291 DOI: 10.1016/j.ejmech.2026.118557
Abstract

Liver injury represents a serious and potentially life-threatening medical condition. Currently, there are no sufficiently targeted or highly effective therapeutic interventions available. Herein, a new series of dual PDE3/4 inhibitors was designed and synthesized for the treatment of liver injury. Among them, compound D5 exhibited IC50 values of 10 and 9.4 nM against PDE3A and PDE4B, respectively, and inhibited the pro-inflammatory factor IL-6 (IC50 = 14.89 μM). In both cholestatic and sepsis-induced liver disease mice models, D5 significantly reduced the expression levels of inflammatory markers in liver tissue and attenuated fibrosis, thereby limiting liver damage. Furthermore, D5 was found to act by modulating the cAMP/PKA/CREB signaling pathway. These findings suggest that the dual PDE3/4 inhibitor D5 is a promising therapeutic candidate for liver injury.

Keywords

Anti-inflammation; Dual PDE3/4 inhibitors; Liver injury.

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