TMEM18 Inhibitors

The chemical class TMEM18 Inhibitors refers to compounds that modulate the activity of the TMEM18 protein indirectly by targeting metabolic pathways and processes in which TMEM18 is implicated. TMEM18 is associated with the regulation of body weight and lipid metabolism, and thus, inhibitors in this class are primarily focused on disrupting lipid regulatory pathways, energy homeostasis, and associated signaling mechanisms.

These inhibitors work by altering the balance of lipid metabolism, which is a key aspect of TMEM18's functional milieu. Orlistat, Simvastatin, Betulinic Acid, GW501516, and others like C75, WY-14643, Fenofibrate, and Rosiglitazone act by modulating enzymatic activities or receptor-mediated pathways that govern the synthesis, breakdown, and storage of lipids. By targeting these critical points in lipid metabolism, such as fatty acid synthesis, cholesterol biosynthesis, and PPAR receptor signaling, these inhibitors can create a cellular environment that may reduce or inhibit TMEM18 activity. For example, Orlistat's inhibition of lipases and Simvastatin's effect on HMG-CoA reductase both lead to changes in lipid absorption and synthesis that can cascade down to affect TMEM18's regulatory functions. In addition, compounds like AICAR, Niclosamide, and Metformin exert their influence by disturbing the energy status of the cell. AICAR and Metformin activate AMPK, a central regulator of cellular energy homeostasis, while Niclosamide decouples mitochondrial oxidative phosphorylation. The activation of AMPK can lead to a variety of downstream effects that promote energy expenditure over storage counteracting the functions of TMEM18 in energy balance and fat storage. On the other hand, Cholestyramine's role in binding bile acids can lead to altered cholesterol homeostasis, which in turn can affect TMThe following table lists chemicals that can indirectly inhibit TMEM18 by influencing related pathways or cellular processes.