Discovery of neuroprotective agents that inhibit human prolyl hydroxylase PHD2

Bioorg Med Chem. 2021 Mar 24;38:116115. doi: 10.1016/j.bmc.2021.116115. Online ahead of print.ABSTRACTProlyl hydroxylase (PHD) enzymes play a critical role in the cellular responses to hypoxia through their regulation of the hypoxia inducible factor α (HIF-α) transcription factors. PHD inhibitors show promise for the treatment of diseases including anaemia, cardiovascular disease and stroke. In this work, a pharmacophore-based virtual high throughput screen was used to identify novel potential inhibitors of human PHD2. Two moderately potent new inhibitors were discovered, with IC50 values of 4 μM and 23 μM respectively. Cell-based studies demonstrate that these compounds exhibit protective activity in neuroblastoma cells, suggesting that they have the potential to be developed into clinically useful neuroprotective agents.PMID:33862469 | DOI:10.1016/j.bmc.2021.116115
Source: Bioorganic and Medicinal Chemistry - Category: Chemistry Authors: Source Type: research