SR-BI Activators

SR-BI Activators are diverse chemical compounds that directly or indirectly enhance the activity of SR-BI, a receptor responsible for the selective uptake of cholesterol esters from high-density lipoprotein (HDL) particles. For instance, Sphingosine-1-phosphate (S1P), a component of the HDL complex, binds to SR-BI and activates downstream PI3K/Akt signaling pathways, promoting cellular cholesterol efflux. BLT1 antagonists indirectly enhance SR-BI's activity by increasing the bioavailability of LTB4, a ligand SR-BI can bind, thus facilitating reverse cholesterol transport. Probucol, through the PPARγ pathway, and Torcetrapib, by raising HDL levels as a CETP inhibitor, both augment the cholesterol uptake function of SR-BI. Notably, LXR and PPAR agonists bolster SR-BI's role in cholesterol metabolism by upregulating its expression, which in turn increases cholesterol efflux to HDL.

Further influencing SR-BI activity are Phosphodiesterase inhibitors, such as Theophylline, which increase intracellular cAMP and subsequently activate PKA, a kinase that phosphorylates SR-BI, thereby enhancing its cholesterol efflux capacity. Ampakines, although primarily involved in neurotransmission, may also indirectly support SR-BI activity by affecting cellular energy states and cholesterol demand. Cholesterol sulfate, an endogenous ligand for SR-BI, directly engages with the receptor to modulate its conformation and optimize the selective uptake of cholesterol esters from HDL.