Recent Advances in Mitochondrial Pyruvate Carrier Inhibitors

Yilei Huang; Han Zhang; Xinyan Peng; Qingwei Zhang

doi:10.1055/s-0044-1788072

Pharmaceutical Fronts, Table of Contents

CC BY 4.0 · Pharmaceutical Fronts 2024; 06(03): e221-e236
DOI: 10.1055/s-0044-1788072

Review Article

Recent Advances in Mitochondrial Pyruvate Carrier Inhibitors

Authors

Yilei Huang

¹Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China

²National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry Co. Ltd., Shanghai, People's Republic of China
Han Zhang

¹Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China

²National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry Co. Ltd., Shanghai, People's Republic of China
Xinyan Peng

¹Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China

³Pharmaceutical Department, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
Qingwei Zhang

¹Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China

²National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry Co. Ltd., Shanghai, People's Republic of China

⁴Shanghai Engineering Research Center of Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry Co., Ltd., Shanghai, People's Republic of China

Abstract

The mitochondrial pyruvate carrier (MPC) exists in the mitochondria inner membrane which transports pyruvate to the mitochondrial matrix. Evidence shows that MPC is the breakthrough point to study the regulation of basic energy metabolism, the dysfunction of which may lead to metabolic disturbance. Due to its important metabolic function, MPC has been considered a potential therapeutic target for diabetes, alopecia, cancers, neurodegenerative diseases, and liver metabolic diseases. However, MPC' protein crystal structure is still not clear as the proteins involved were only identified 10 years ago, making it difficult to carry out rational drug design based on receptor structure. In this review, we summarize the latest applications of MPC in different diseases and discuss the recent advances in pharmacochemical strategies of small-molecule inhibitors of MPC, hoping to promote the development of specific MPC inhibitors.

Keywords

metabolism - mitochondrial pyruvate carrier - MPC inhibitors

Full Text

References

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