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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

Yilei Huang
1   Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
2   National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry Co. Ltd., Shanghai, People's Republic of China
,
Han Zhang
1   Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
2   National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry Co. Ltd., Shanghai, People's Republic of China
,
Xinyan Peng
1   Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
3   Pharmaceutical Department, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
,
Qingwei Zhang
1   Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
2   National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry Co. Ltd., Shanghai, People's Republic of China
4   Shanghai 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
› Author Affiliations Funding This work was supported by the National Science and Technology Major Project (Grant No. 2018ZX09711002-002-009), the National Natural Science Foundation of China (Grant No. 81703358), the Science and Technology Commission of Shanghai Municipality (Grant Nos. 17431903900, 18QB1404200, 21S11908000, 22ZR1460300, 23DZ2292600), and the National Key Laboratory of Lead Druggability Research (Grant No. NKLYT2023004).
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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


Publication History

Received: 30 January 2024

Accepted: 17 June 2024

Article published online:
15 July 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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