TLX agonist 3 is a potent and selective tailless homolog (TLX, NR2E1) agonist, with an EC50 of 0.25 μM and a Kd of 1.6 μM. It exhibits high selectivity for related nuclear receptors and enhances TLX oligomerization (EC50 = 5.0 μM). TLX agonist 3 is applicable in research on neurodegenerative diseases.

TLX:0.25 μM (EC50)

TLX agonist 3 (compound 10) enhances TLX oligomerization in a concentration-dependent manner during homogeneous time-resolved fluorescence resonance energy transfer (HTRF) assays at concentrations of 2.5-20 μM over 22 hours. In HEK293 cells, it activates full-length human TLX with an EC50 of 0.7 μM. TLX agonist 3 (3 μM; 8 hours) induces expression of SIRT1 in T98G human astrocyte cells without changing TLX levels. It demonstrates good stability in rat liver microsomes at a concentration of 10 μM with a half-life of 142 minutes over 0-60 minutes and shows no significant cytotoxic effects in HEK293 cells at concentrations up to 10 μM over 24 hours. Real Time qPCRCell Line: T98G human astrocyte cells, Concentration: 3 μM, Incubation Time: 8 h, Result: Induced expression of the TLX-regulated gene SIRT1 but did not alter TLX levels.