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Updated: Jan 29, 2026

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation

Published on: February 28, 2019

システム最適化フラグメントTLXリガンドによるアゴニズムとインバースアゴニズムの実現

Emily C Hank¹, Loris Knümann¹, Úrsula López-García¹

¹Department of Pharmacy, Ludwig-Maximilians-Universität München, Munich 81377, Germany.

Journal of medicinal chemistry

|January 28, 2026

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.

キーワード:

神経保護 TLX 神経幹細胞低分子アゴニストインバースアゴニスト神経発生創薬

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