Recent Advances in Mitochondrial Pyruvate Carrier Inhibitors

Yilei Huang, Han Zhang, Xinyan Peng, Qingwei Zhang
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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.
线粒体丙酮酸载体抑制剂的最新进展
线粒体丙酮酸载体(MPC)存在于线粒体内膜,它将丙酮酸运送到线粒体基质。有证据表明,MPC 是研究基本能量代谢调节的突破点,其功能障碍可能导致代谢紊乱。由于其重要的代谢功能,MPC 被认为是糖尿病、脱发、癌症、神经退行性疾病和肝脏代谢疾病的潜在治疗靶点。然而,由于 MPC 蛋白的晶体结构在 10 年前才被确定,因此其晶体结构至今仍不清楚,这使得根据受体结构进行合理的药物设计变得十分困难。在这篇综述中,我们总结了 MPC 在不同疾病中的最新应用,并讨论了 MPC 小分子抑制剂药理化学策略的最新进展,希望能促进特异性 MPC 抑制剂的开发。
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