2. Academic Validation
  3. A retrospective overview of PHGDH and its inhibitors for regulating cancer metabolism

A retrospective overview of PHGDH and its inhibitors for regulating cancer metabolism

  • Eur J Med Chem. 2021 May 5;217:113379. doi: 10.1016/j.ejmech.2021.113379.
Jia-Ying Zhao 1,  Kai-Rui Feng 1,  Feng Wang 1,  Jian-Wei Zhang 1,  Jay Fei Cheng 2,  Guo-Qiang Lin 3,  Dingding Gao 4,  Ping Tian 5
Affiliations

Affiliations

  • 1 The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China.
  • 2 The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China. Electronic address: jay.f.cheng@outlook.com.
  • 3 The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China; CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
  • 4 The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China. Electronic address: gaodingding@shutcm.edu.cn.
  • 5 The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China; CAS Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China. Electronic address: tianping@shutcm.edu.cn.
PMID: 33756126 DOI: 10.1016/j.ejmech.2021.113379
Abstract

Emerging evidence suggests that Cancer metabolism is closely associated to the serine biosynthesis pathway (SSP), in which glycolytic intermediate 3-phosphoglycerate is converted to serine through a three-step enzymatic transformation. As the rate-limiting Enzyme in the first step of SSP, phosphoglycerate dehydrogenase (PHGDH) is overexpressed in various diseases, especially in Cancer. Genetic knockdown or silencing of PHGDH exhibits obvious anti-tumor response both in vitro and in vivo, demonstrating that PHGDH is a promising drug target for Cancer therapy. So far, several types of PHGDH inhibitors have been identified as a significant and newly emerging option for Anticancer treatment. Herein, this comprehensive review summarizes the recent achievements of PHGDH, especially its critical role in Cancer and the development of PHGDH inhibitors in drug discovery.

Keywords

Cancer metabolism; Inhibitors; Phosphoglycerate dehydrogenase; Serine biosynthesis pathway.

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