# High-Throughput Screening of Potent Drug-like Molecules Targeting 17β-HSD10 for the Treatment of Alzheimer’s Disease and Cancer

## TL;DR

This study screens thousands of molecules to find new drugs targeting an enzyme linked to Alzheimer's and cancer.

## Contribution

The first industrial-scale high-throughput screening of molecules targeting 17β-HSD10 is conducted, identifying novel inhibitors.

## Key findings

- Two novel series of potent 17β-HSD10 inhibitors with low nanomolar potency were identified.
- The inhibitors showed minimal cytotoxicity and were characterized via ligand–protein interactions and co-crystallography.
- The inhibitors demonstrate un-/non-competitive inhibition with respect to NADH, differing from prior inhibitors.

## Abstract

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.