2. Academic Validation
  3. The SAR and action mechanisms of autophagy inhibitors that eliminate drug resistance

The SAR and action mechanisms of autophagy inhibitors that eliminate drug resistance

  • Eur J Med Chem. 2022 Dec 15:244:114846. doi: 10.1016/j.ejmech.2022.114846.
Wenchong Ye 1,  Chuangchuang Fan 2,  Kaishou Fu 3,  Xiaoyang Wang 4,  Jingchao Lin 5,  Sihui Nian 6,  Chunhui Liu 7,  Wen Zhou 8
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, E. 232, University Town, Waihuan Rd, Panyu, Guangzhou, 510006, Guangdong, China; Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 200241, Shanghai, China.
  • 2 School of Pharmacy, Wannan Medical College, Wuhu, 241002, Anhui Province, China.
  • 3 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, E. 232, University Town, Waihuan Rd, Panyu, Guangzhou, 510006, Guangdong, China.
  • 4 Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 200241, Shanghai, China.
  • 5 Metabo-Profile Biotechnology (Shanghai) Co. Ltd., 201315, Shanghai, China.
  • 6 School of Pharmacy, Wannan Medical College, Wuhu, 241002, Anhui Province, China. Electronic address: niansihui@126.com.
  • 7 Key Laboratory of Chemical Biology (Ministry of Education), Institute of Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, Shandong, PR China. Electronic address: liuchunhui@sdu.edu.com.
  • 8 Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 200241, Shanghai, China. Electronic address: zhouwen60@126.com.
PMID: 36283182 DOI: 10.1016/j.ejmech.2022.114846
Abstract

Autophagy is an essential homeostatic and catabolic process crucial for the degradation or recycling of proteins and cellular components. Drug resistance has been demonstrated to be closely implicated in increased Autophagy. Autophagy inhibition to reverse drug resistance involves in the five stages of Autophagy, including phagophore initiation, vesicle nucleation, vesicle elongation, vesicle fusion and cargo degradation. Herein, emphases were placed on discussions on the targets responsible for the upstream phagophore initiation and nucleation of autophagosome, as well as the ones mediating the downstream autophagosome and lysosome fusion and cargo degradation. The structure-activity relationships (SARs) and action mechanisms of the corresponding target-based small molecule Autophagy inhibitors were analyzed and delineated. This review will provide a promising guidance for the design and optimization of drug-like scaffolds in the discovery of Autophagy inhibitors able to eliminate drug resistance.

Keywords

Action mechanisms; Autophagy; Autophagy inhibitors; Drug resistance; Structure-activity relationships (SARs).

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