HM74A activators constitute a group of compounds that can interact with the Hydroxycarboxylic acid receptor 2, either directly or indirectly, to modulate its activity. This receptor plays a significant role in metabolic regulation, particularly in the context of lipid metabolism and energy homeostasis. The activators identified span a range of compounds that interact with metabolic pathways, highlighting the multifaceted approach to influencing HM74A activity. Direct activators like Lactate and Nicotinic acid are known to bind HM74A and activate its signaling pathways. Lactate, an endogenous ligand, directly engages with HM74A, triggering downstream signaling cascades that influence various metabolic processes. Nicotinic acid, or Niacin, a well-documented activator of HM74A, exerts anti-lipolytic effects through its interaction with the receptor. Other direct activators, such as Monomethyl fumarate and 3-Hydroxybutyrate, may activate HM74A due to their structural similarities to known ligands or their roles in metabolic pathways.Indirect activators, including PPARγ agonists like Pioglitazone and Rosiglitazone, influence adipocyte function and lipid metabolism, thereby modulating HM74A activity. Acipimox, a Niacin analogue, also activates HM74A, affecting lipid metabolism. Omega-3 fatty acids such as DHA and EPA, through their roles in lipid metabolism, could indirectly influence HM74A activity, demonstrating the interplay between dietary components and receptor modulation. Additionally, compounds like Berberine, Curcumin, and Resveratrol, known for their broad metabolic effects, could indirectly activate HM74A. These compounds modulate various signaling pathways and metabolic processes, which can lead to changes in HM74A activity.