High-Throughput Screening of Potent Drug-like Molecules Targeting 17β-HSD10 for the Treatment of Alzheimer’s Disease and Cancer
Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide In this study, the first industrial-scale high-throughput screening of nearly 350,000 drug-like molecules targeting the enzyme 17β-HSD10, a promising therapeutic target for Alzheimer’s disease and cancers, is presented. Two novel series of potent 17β-HSD10 inhibitors that demonstrate low nanomolar potency against both the enzyme and in vivo cellular assays with minimal cytotoxicity were identified. These inhibitors were characterized further through a series of assays demonstrating ligand–protein interactions and co-crystallography, revealing un-/non-competitive inhibition with respect to the cofactor NADH, unlike previously published inhibitors. This work significantly advances the development of 17β-HSD10-targeting therapeutics, offering new potential leads for treating Alzheimer’s disease and cancers.
Source: ACS Chemical Biology
Authors: Laura Aitken, Gemma Baillie, Andrew Pannifer, Angus Morrison, Louise L. Major, Magnus S. Alphey, Ritika Sethi, Martin Timmerman, John Robinson, Jennifer Riley, Yoko Shishikura, Lizbe Koekemoer, Frank Von Delft, Helma Rutjes, Kevin D. Read, Philip S. Jones, Stuart P. McElroy, Terry K. Smith, Frank J. Gunn-Moore
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W4411417598