RORγ Activator

Lumisterol (9β,10α-Ergosterol) is a photoproduct of 7-dehydrocholesterol, present in the skin, and acts as an orally active VDR non-genomic modulator and ROR inverse agonist. Lumisterol binds to the SARS-CoV-2 Mpro substrate-binding pocket and the RdRP active site, inhibiting enzyme activity. Lumisterol induces NRF2-regulated antioxidant responses, p53 phosphorylation and nuclear translocation, and intracellular free radical scavenging. Lumisterol inhibits the proliferation of epidermal keratinocytes and melanoma cells, modulates cell cycle progression, and suppresses basal and TNFα-induced NFκB transcriptional activity. Lumisterol inhibits RORγ transcriptional activity and IL-17 production. Lumisterol is used in research on UVB-induced skin damage, melanoma, psoriasis, vitamin D deficiency, and COVID-19.

7ß,27-Dihydroxycholesterol (7β, 27-OHC) is a potent and selective activator of RORγt (K_i=120 nM). 7ß,27-Dihydroxycholesterol promotes the differentiation of mouse and human CD4⁺ Th17 cells. 7ß,27-Dihydroxycholesterol also increases the production of IL-17 depended on CYP27A1.