ROR 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.

6'''-Feruloylspinosin is an orally active RORα activator that crosses the blood-brain barrier, with a K_d of 0.308 μM, and is found in natural sources. 6'''-Feruloylspinosin modulates AMPK and mTOR phosphorylation. 6'''-Feruloylspinosin promotes autophagy through the AMPK/mTOR signaling pathway, inhibits GSK3β phosphorylation at Tyr216, and activates the PGC-1α/Nrf2/HO-1 pathway. 6'''-Feruloylspinosin regulates neurotransmitter levels, enhances mRNA expression of GABA_A α1, α5, and GABA_B R1 receptor subunits, increases brain 5-HT and GABA, restores melatonin levels, and ameliorates anxiety-like behaviors. 6'''-Feruloylspinosin regulates oxidative stress homeostasis, inhibits mitochondrial dysfunction, decreases MDA while increasing GSH. 6'''-Feruloylspinosin can be used for research on Alzheimer's disease, acute myocardial infarction, heart failure with insomnia, and insomnia.

CM002 is a circadian clock activator. CM002 inhibits the lineage commitment and terminal differentiation of preadipocytes by activating the circadian clock, thereby blocking the adipogenesis process driven by Wnt signaling-mediated transcriptional induction. CM002 attenuates lipid storage in a clock-dependent manner via inhibition of the lipogenic program in mature adipocytes. CM002 enhances circadian clock output across various adipose depots in both lean and obese mice through BMAL1/CLOCK-dependent metabolic reprogramming, inhibits adipocyte development and hypertrophy, and improves insulin sensitivity. CM002 can be used in research on obesity and type 2 diabetes.

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.