Lycorine

Lycorine is a natural alkaloid extracted from the Amaryllidaceae plant. Lycorine is a potent and orally active SCAP inhibitor with a K_d value 15.24 nM. Lycorine downregulates the SCAP protein level without changing its transcription^[2]. Lycorine is also a melanoma vasculogenic inhibitor^[3]. Lycorine can be used for the study of prostate cancer and metabolic diseases^[2].
IC50 & Target:Kd: 15.24 nM (SCAP)^[1] In Vitro: Lycorine inhibits cell proliferation in a dose-dependent manner in the abovementioned 4 PCa cell lines, and the IC₅₀ ranged from 5 μM to 10 μM., it also shows Lycorine has little effects on PNT1A cell's proliferation^[1].
SCAP (SREBF chaperone) is an ER-toGolgi transport protein, undergoes a conformational change, and regulates/preserves SREBFs in the ER by forming a complex with INSIG1 (insulin induced gene 1)^[2].
Lycorine (5-40 μM; 16 hours) significantly suppresses SREBFs activity (up to -70%) in a dosedependent manner and does not cause obvious cytotoxicity in cells^[2].
Lycorine (10-20 μM; 2-16 hours) dose- and time-dependently decreases the mature SREBF1 and SREBF2 proteins in HL-7702 cells^[2].
Lycorine (20 μM; 16 hours) neither activates NR1H3 transcription nor affect NR1H3 target genes, including ABCG5 and ABCG8, but Sterols activates NR1H3 transcription activity^[1].
Lycorine hydrochloride (0-25 μM; 48 hours) treatment markedly suppresses the expression of vascular endothelial (VE)-cadherin in a dose-dependent manner and also slightly diminishes the expression of Sema4D in C8161 cells. However, the expression of the other six genes is not affected^[3].
Lycorine hydrochloride (0-25 μM; 48 hours) treatment markedly reduces VE-cadherin protein levels in C8161 cells in a dose-dependent fashion^[3].
In Vivo: Lycorine (oral chow; 15 mg/kg, 30 mg/kg; once daily) alleviates fat accumulation and metabolic syndrome, increases lipolysis and betaoxidation of fatty acid along with precursor and mature SREBFs in mice ^[2].