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- Title
Selective Inhibitors of a Human Prolyl Hydroxylase (OGFOD1) Involved in Ribosomal Decoding.
- Authors
Thinnes, Cyrille C.; Lohans, Christopher T.; Abboud, Martine I.; Yeh, Tzu‐Lan; Tumber, Anthony; Nowak, Radosław P.; Attwood, Martin; Cockman, Matthew E.; Oppermann, Udo; Loenarz, Christoph; Schofield, Christopher J.
- 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. Humans have 60–70 2OG‐dependent oxygenases, of which some are important therapeutic targets. A priority in the development of oxygenase inhibitors is to identify scaffolds selective for a particular enzyme, made challenging by the highly conserved oxygenase active sites. This work reports the development of potent inhibitors for the oxygenase OGFOD1, which do not inhibit related enzymes, such as the physiologically important oxygenase PHD2.
- Subjects
CRYSTAL structure; NANOPARTICLES; POLYCYTHEMIA; HYPOXIA-inducible factors; HYDROXYLASES
- Publication
Chemistry - A European Journal, 2019, Vol 25, Issue 8, p2019
- ISSN
0947-6539
- Publication type
Article
- DOI
10.1002/chem.201804790