TO-901317

TO-901317 is a synthetic small molecule that acts as a potent and selective agonist of the liver X receptors (LXRα and LXRβ), which are ligand-dependent nuclear transcription factors involved in the regulation of cholesterol homeostasis and lipid metabolism[1][2][3]. It is a nonsterol benzenesulfonamide compound with high affinity for both LXR isoforms (EC₅₀ ≈ 20 nM for LXRα)[3]. In preclinical studies, TO-901317 has been shown to inhibit the development of atherosclerosis in LDL receptor-deficient mice without affecting plasma total cholesterol levels[1], improve hepatic glucose metabolism and insulin resistance by reducing oxidative stress and suppressing JNK pathway activation via LXRs[4], modulate neuroinflammation markers such as iNOS and COX2 through NFκB signaling pathways[7], reduce diacylglycerol accumulation in diabetic hearts[5], and increase hippocampal precursor proliferation in mouse models relevant to neurodevelopmental disorders[8]. It also exhibits inverse agonist activity at retinoic acid receptor-related orphan receptors (RORα/γ) and can activate farnesoid X receptor (FXR) at higher concentrations[6][9]. The compound is primarily used experimentally as a research tool; it has not been approved for clinical use.

Other names

N-(2,2,2-Trifluoroethyl)-N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]benzenesulfonamide