Selective Inhibitors of a Human Prolyl Hydroxylase (OGFOD1) Involved in Ribosomal Decoding.

Abstract

Human prolyl hydroxylases are involved in the modification of transcription factors, procollagen, and ribosomal proteins, and are current medicinal chemistry targets. To date, there are few reports on inhibitors selective for the different types of prolyl hydroxylases. We report a structurally informed template-based strategy for the development of inhibitors selective for the human ribosomal prolyl hydroxylase OGFOD1. These inhibitors did not target the other human oxygenases tested, including the structurally similar hypoxia-inducible transcription factor prolyl hydroxylase, PHD2.

• Authors: Cyrille C Thinnes, Christopher T Lohans, Martine I Abboud, Tzu-Lan Yeh, Anthony Tumber, Radosław P Nowak, Martin Attwood, Matthew E Cockman, Udo Oppermann, Christoph Loenarz, Christopher J Schofield
• Journal: Chemistry (Weinheim an der Bergstrasse, Germany) (Chemistry) Vol. 25 Issue 8 Pg. 2019-2024 (Feb 06 2019) ISSN: 1521-3765 [Electronic] Germany
• PMID: 30427558 (Publication Type: Journal Article)
• Copyright: © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Chemical References

• Carrier Proteins
• Nuclear Proteins
• OGFOD1 protein, human
• Prolyl-Hydroxylase Inhibitors
• Prolyl Hydroxylases

Topics

• Carrier Proteins (antagonists & inhibitors)
• Drug Design
• Humans
• Nuclear Proteins (antagonists & inhibitors)
• Prolyl Hydroxylases (metabolism)
• Prolyl-Hydroxylase Inhibitors (chemistry, metabolism, pharmacology)
• Ribosomes (drug effects, metabolism)
• Structure-Activity Relationship
• Substrate Specificity