DECR1 Inhibitors

DECR1 inhibitors are a class of compounds that influence the activity of 2,4-dienoyl-CoA reductase indirectly by affecting the fatty acid metabolism within which DECR1 operates. These inhibitors function primarily by altering the availability of substrates for the enzyme or by changing the enzyme's regulatory environment. Compounds like etomoxir, perhexiline, and malonyl-CoA function by inhibiting enzymes upstream of DECR1, such as CPT1, which is responsible for the transport of long-chain fatty acids into mitochondria. By reducing the influx of fatty acids into the mitochondria, these inhibitors lower the substrate availability for the beta-oxidation pathway, thereby reducing the need for DECR1 activity.On the other hand, compounds such as fenofibrate and gemfibrozil activate PPARα, a nuclear receptor that regulates the expression of genes involved in fatty acid metabolism, including those involved in the beta-oxidation pathway. The activation of PPARα can lead to increased fatty acid oxidation, which may alter the activity of DECR1 indirectly. Additionally, molecules like metformin and nicotinic acid can modify the systemic metabolic state, which in turn can influence the activity of enzymes involved in fatty acid metabolism, such as DECR1. In essence, DECR1 inhibitors comprise a diverse group of compounds that modulate the mitochondrial and cellular metabolism of fatty acids, thereby impacting the enzymatic activity of DECR1 without directly interacting with the enzyme itself. These compounds achieve this by either reducing the availability of substrates or altering the expression and regulation of key metabolic pathways.