@article {897,
	title = {Gliflozins, sucrose and flavonoids are allosteric activators of lecithin-cholesterol acyltransferase},
	journal = {Scientific Reports},
	volume = {14},
	year = {2024},
	month = {2024/10/30/},
	pages = {26085},
	abstract = {Abstract            Lecithin-cholesterol acyltransferase (LCAT) serves as a pivotal enzyme in preserving cholesterol homeostasis via reverse cholesterol transport, a process closely associated with the onset of atherosclerosis. Impaired LCAT function can lead to severe LCAT deficiency disorders for which no pharmacological treatment exists. LCAT-based therapies, such as small molecule positive allosteric modulators (PAMs), against LCAT deficiencies and atherosclerosis hold promise, although their efficacy against atherosclerosis remains challenging. Herein we utilized a quantitative in silico metric to predict the activity of novel PAMs and tested their potencies with in vitro enzymatic assays. As predicted, sodium-glucose cotransporter 2 (SGLT2) inhibitors (gliflozins), sucrose and flavonoids activate LCAT. This has intriguing implications for the mechanism of action of gliflozins, which are commonly used in the treatment of type 2 diabetes, and for the endogenous activation of LCAT. Our results underscore the potential of molecular dynamics simulations in rational drug design.},
	isbn = {2045-2322},
	doi = {10.1038/s41598-024-77104-3},
	url = {https://www.nature.com/articles/s41598-024-77104-3}
}
