Auer Manfred, Walkinshaw Malcolm D, Dornan Jacqueline, Pham Nhan T, Xue Xinru, Liu Miaomiao, Quinn Ronald J, Ross Eric M, Rodríguez Abimael D, La Clair James J
Xenobe Research Institute, P.O. Box 3052, San Diego, CA 92163-1052, USA.
School of Biological Sciences, University of Edinburgh, The King's Buildings, Edinburgh EH9 3BF, UK.
Mar Drugs. 2025 Aug 24;23(9):336. doi: 10.3390/md23090336.
While immunophilins are well-recognized therapeutic targets, several members of this family of peptidyl-proline isomerases (PPIases) have yet to be subjected to ligand discovery efforts. In this study, we demonstrate a cost-effective means to identify ligands to the insufficiently investigated two-domain PPIase human Cyclophilin40 (Cyp40). Central to this effort was the use of beads, wherein a confocal nanoscanning (CONA) approach was used to rapidly probe candidates. Here, we describe how one can adapt the physical nature of microsized beads as a means to strategically reduce cost and ultimately make the discovery of small molecule hit and lead compounds more accessible to everyone irrespective of financial status (democratization).
虽然免疫亲和素是公认的治疗靶点，但该肽基脯氨酸异构酶（PPIase）家族的几个成员尚未进行配体发现研究。在本研究中，我们展示了一种经济高效的方法来识别尚未充分研究的双结构域PPIase人亲环蛋白40（Cyp40）的配体。这项工作的核心是使用珠子，其中采用共聚焦纳米扫描（CONA）方法快速探测候选物。在这里，我们描述了如何利用微米级珠子的物理性质，作为一种从战略上降低成本的手段，并最终使发现小分子命中和先导化合物对每个人来说都更容易实现，而不论其经济状况如何（民主化）。
