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Recent Advances on PKM2 Inhibitors and Activators in Cancer Applications

Peng Chen¹, Liang Lou¹, Bigyan Sharma¹

¹School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen 518107, P.R. China.

Current Medicinal Chemistry

|July 17, 2023

Abstract:

Metabolic reprogramming of cells, from the normal mode of glucose metabolism named glycolysis, is a pivotal characteristic of impending cancerous cells. Pyruvate kinase M2 (PKM2), an important enzyme that catalyzes the final rate-limiting stage during glycolysis, is highly expressed in numerous types of tumors and aids in development of favorable conditions for the survival of tumor cells. Increasing evidence has suggested that PKM2 is one of promising targets for innovative drug discovery, especially for the developments of antitumor therapeutics. Herein, we systematically summarize the recent advancement on PKM2 modulators including inhibitors and activators in cancer applications. We also discussed the classifications of pyruvate kinases in mammals and the biological functions of PKM2 in this review. We do hope that this review would provide a comprehensive understanding of the current research on PKM2 modulators, which may benefit the development of more potent PKM2-related drug candidates to treat PKM2-associated diseases including cancers in future.

Insights

Cancer cells reprogram glucose metabolism via pyruvate kinase M2 (PKM2). This review summarizes PKM2 modulators, like inhibitors and activators, for developing novel antitumor drugs targeting PKM2 in cancer treatment.

Area of Science:

Biochemistry and Molecular Biology
Cancer Research
Drug Discovery

Background:

Metabolic reprogramming, specifically altered glycolysis, is a hallmark of cancer.
Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme overexpressed in tumors, promoting cancer cell survival.
PKM2 is recognized as a promising therapeutic target for novel anticancer drug development.

Purpose of the Study:

To systematically review recent advancements in PKM2 modulators (inhibitors and activators) for cancer applications.
To discuss the classification of mammalian pyruvate kinases and the biological functions of PKM2.
To provide a comprehensive understanding of current PKM2 research to aid future drug development for PKM2-associated diseases.

Main Methods:

Systematic review of recent scientific literature on PKM2 modulators.
Analysis of PKM2's role in cancer metabolism and cell survival.
Discussion of PKM2 classification and biological functions.

Main Results:

PKM2 plays a critical role in cancer cell glycolysis and survival.
Various PKM2 inhibitors and activators have been developed as potential anticancer therapeutics.
Understanding PKM2's functions is crucial for targeted cancer drug design.

Conclusions:

PKM2 is a significant target for developing innovative antitumor drugs.
This review consolidates current knowledge on PKM2 modulators, facilitating the development of potent PKM2-related drug candidates.
Further research into PKM2 modulators holds promise for treating various cancers and PKM2-associated diseases.

Read full analysis

Keywords:

PKM2 activators antitumor biomedical applications inhibitors modulators.

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