Liver X receptor agonist,potent and selective
CAS：293754-55-9
分子式：C17H12F9NO3S
分子量：481.33
纯度：98%
存储：Store at -20°C

Background:

T0901317 is an agonist for multiple targets, which possesses EC50 values of 20 nM and 5 μM for LXRα and FXR, respectively. Furthermore, it is RORα and RORγ dual inverse agonist with estimated IC50 of 2.0 μM and 1.7 μM, respectively. [1, 2]

LXRs play central roles in cholesterol metabolism, which are nuclear receptors that regulate the metabolism of several important lipids, including cholesterol and bile acids. LXRs were first identified as orphan members of the nuclear receptor superfamily. Like LXRs, FXR was also initially thought as an orphan member of the nuclear receptor superfamily. But FXR was later identified as the physiological receptor for bile acids and shown to regulate a feedback loop for bile acid transport and synthesis as well as modulating additional functions in lipid metabolism. Retinoic acid receptor-related orphan receptors (RORs) are important in a variety of physiological processes including hepatic gluconeogenesis, lipid metabolism, circadian rhythm, and immunological functions. T0901317 inhibited transactivation activity of RORα and RORγ by direct binding with high affinity which led to the regulation of the receptor’s ability to interact with transcriptional cofactor proteins, but did not show inhibitory activity against RORβ. [1, 2]

A short synthetic rhodamine-labeled peptide was used to conduct a fluorescence polarization assay for T0901317 binding to LXRα. In this homogeneous biochemical assay, the greater the extent of rhodamine-peptide binding to LXR, the greater the extent of fluorescence polarization observed. The potency of T0901317 binding to LXRα was determined, which possessed EC50 of 20 nM. Adopting HEK293 cells transfected with Gal4 DBD-FXR ligand-binding-domain chimeric receptor along with Gal4-responsive luciferase reporter, T0901317 activated FXR with an EC50 of