Lipoic acid can be used as a coenzyme to participate in the acyl transfer of material metabolism in the body. Besides, lipoic acid can eliminate free radicals, which leads to accelerated aging and disease. Generally speaking, intestine absorbs lipoic acid and then it enters the cell. Moreover, lipoic acid is both fat soluble and water soluble.
Mitochondria use multiple carbon fuels to produce ATP and metabolites. In quick succession, these carbon fuels feed into the TCA cycle in the mitochondrial matrix to generate the reducing equivalents NADH and FADH2. Furthermore, mitochondria are complex organelles that play an important role in many facets of cellular function, from metabolism to immune regulation and cell death. Mitochondrial metabolism is a key determinant of tumor progression by impacting on functions such as epithelial-to-mesenchymal transition. Mitochondrial metabolism and derived oncometabolites shape the epigenetic landscape to alter aggressiveness features of cancer cells. Changes in mitochondrial metabolism are relevant for the survival of tumors in response to therapy.
Here, we focus on the lipoic acid antagonist, Devimistat.
Devimistat, a lipoic acid antagonist, is a mitochondrial metabolism inhibitor. It is worth noting, mitochondria as a necessary cofactor, synthesizes lipoic acids, during mitochondrial energy metabolism. Lipoic acids have been shown to decrease cell viability and proliferation in cancer, such as head and neck cancer. Notably, Devimistat abrogates mitochondrial energy metabolism to induce apoptosis in various cancer cells. Specifically, Devimistat targets the altered form of mitochondrial energy metabolism utilized by tumor cells. Moreover, Devimistat induces the change in mitochondrial enzyme activities and cellular redox status, leading to cell death, including apoptosis. In vitro, Devimistat induces apoptosis of GPM-2 gastric cancer cells.
Taken together, Devimistat, a lipoic acid antagonist, is a mitochondrial metabolism inhibitor.