Development of Tailless Homologue Receptor (TLX) Agonist Chemical Tools,Journal of Medicinal Chemistry

当前位置： X-MOL 学术 › J. Med. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Development of Tailless Homologue Receptor (TLX) Agonist Chemical Tools
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2024-09-05 , DOI: 10.1021/acs.jmedchem.4c01443
Emily C Hank ₁ , Minh Sai ₁ , Till Kasch ₁ , Isabelle Meijer ₁ , Julian A Marschner ₁ , Daniel Merk ₁

Affiliation

The human tailless homologue receptor (TLX) is a ligand-activated transcription factor acting as a master regulator of neural stem cell homeostasis. Despite its promising potential in neurodegenerative disease treatment, TLX ligands are rare but required to explore phenotypic effects of TLX modulation and for target validation. We have systematically studied and optimized a TLX agonist scaffold obtained by fragment fusion. Structural modification enabled the development of two TLX agonists endowed with nanomolar potency and binding affinity. Both exhibited favorable chemical tool characteristics including high selectivity and low toxicity. Most notably, the TLX agonists comprise different scaffolds and display high chemical diversity, enabling their use as a set for target identification and validation studies.

中文翻译：

无尾同系物受体（TLX）激动剂化学工具的开发

人无尾同源受体（TLX）是一种配体激活的转录因子，是神经干细胞稳态的主要调节因子。尽管 TLX 配体在神经退行性疾病治疗方面具有广阔的潜力，但它很少见，但需要探索 TLX 调节的表型效应和靶标验证。我们系统地研究和优化了通过片段融合获得的 TLX 激动剂支架。结构修饰使两种具有纳摩尔效力和结合亲和力的 TLX 激动剂得以开发。两者都表现出良好的化学工具特性，包括高选择性和低毒性。最值得注意的是，TLX 激动剂包含不同的支架并显示出高度的化学多样性，使其能够用作靶标识别和验证研究的集合。

更新日期：2024-09-05

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南