Year: 2026
Type: article
Abstract: The transcription factor tailless homologue (TLX, NR2E1) maintains persistence of neural stem cells (NSCs) in a proliferating, undifferentiated state, thereby controlling NSC homeostasis and enabling neurogenesis. TLX is responsive to small-molecule ligands, offering potential access to new neuroprotective treatments, but TLX ligands are very rare. Here, we used a drug fragment screening hit as lead to develop TLX modulators and identified substructures tuning activity between agonism and inverse agonism. Structural optimization provided potent TLX activating and inhibiting fragment ligands with validated binding and favorable ligand efficiency for structural extension.
Source: Journal of Medicinal Chemistry
Institution: Ludwig-Maximilians-Universität München
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7125956563