A5077048997- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- Metabolomics and Mass Spectrometry Studies
- Effects of Radiation Exposure
- Radiopharmaceutical Chemistry and Applications
- Metabolism, Diabetes, and Cancer
- Cancer Research and Treatments
- Genetics and Neurodevelopmental Disorders
- ATP Synthase and ATPases Research
- Click Chemistry and Applications
- Hemoglobin structure and function
- Catalytic C–H Functionalization Methods
- Pancreatic function and diabetes
- Monoclonal and Polyclonal Antibodies Research
- Synthesis and Catalytic Reactions
- Radiation Therapy and Dosimetry
- Chemical Synthesis and Analysis
- Metal-Catalyzed Oxygenation Mechanisms
- Lanthanide and Transition Metal Complexes
- High Altitude and Hypoxia
Oxford Research Group
2016-2025
University of Oxford
2014-2019
Oxfam
2017-2018
Science Oxford
2015
Four compounds in clinical trials for anaemia treatment are potent inhibitors of the hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs), but differ potency and how they interact with HIF at PHD active site.
The 2-oxoglutarate (2OG)-dependent Jumonji C domain (JmjC) family is the largest of histone lysine demethylases. There interest in developing small-molecule probes that modulate JmjC activity to investigate their biological roles. 5-Carboxy-8-hydroxyquinoline (IOX1) most potent broad-spectrum inhibitor 2OG oxygenases, including demethylases, reported date; however, it suffers from low cell permeability. Here, we describe structure-activity relationship studies leading discovery an n-octyl...
A Betti reaction was used for efficient generation of 2OG oxygenase inhibitors, including KDM4 demethylases.
Abstract The mechanism of Amifostine (WR-2721) mediated radioprotection is poorly understood. effects amifostine on human basal metabolism, mouse liver metabolism and normal tumor hepatic cells were studied. Indirect calorimetric canopy tests showed significant reductions in oxygen consumption carbon dioxide emission cancer patients receiving amifostine. Glucose levels significantly decreased lactate increased patient venous blood. Although vitro did not inhibit the activity...
Tight, non-active site binding cyclic peptides are promising affinity reagents for studying proteins and their interactions.
The 2-oxoglutarate-dependent hypoxia inducible factor prolyl hydroxylases (PHDs) are targets for treatment of a variety diseases including anaemia. One PHD inhibitor is approved use the renal anaemia and others in late stage clinical trials. number reported templates inhibition limited. We report structure-activity relationship crystallographic studies on promising class 4-hydroxypyrimidine-containing inhibitors.
Abstract Human prolyl hydroxylases are involved in the modification of transcription factors, procollagen, and ribosomal proteins, current medicinal chemistry targets. To date, there few reports on inhibitors selective for different types hydroxylases. We report a structurally informed template‐based strategy development human hydroxylase OGFOD1. These did not target other oxygenases tested, including similar hypoxia‐inducible factor hydroxylase, PHD2.
Prolyl hydroxylation domain (PHD) enzymes catalyze the of transcription factor hypoxia-inducible (HIF) and serve as cellular oxygen sensors. HIF PHD regulate numerous potentially tissue-protective target genes which can adapt cells to metabolic ischemic stress. We describe a fluorescent inhibitor (1-chloro-4-hydroxybenzo[g]isoquinoline-3-carbonyl)glycine is suited fluorescence-based detection assays for monitoring inhibitors in biological systems. In cell-based assays, application allowed...
Fe(II)- and 2-oxoglutarate (2OG)-dependent JumonjiC domain-containing histone demethylases (JmjC KDMs) are epigenetic eraser enzymes involved in the regulation of gene expression emerging drug targets oncology. We screened a set clinically used iron chelators report that they potently inhibit JMJD2A (KDM4A) vitro. Mode action investigations revealed one compound, deferasirox, is bona fide active site-binding inhibitor as shown by kinetic spectroscopic studies. Synthesis derivatives with...
Fe(II)- and 2-oxoglutarate (2OG)-dependent JumonjiC domain-containing histone demethylases (JmjC KDMs) are epigenetic eraser enzymes involved in the regulation of gene expression emerging drug targets oncology. We screened a set clinically used iron chelators report that they potently inhibit JMJD2A (KDM4A) vitro. Mode action investigations revealed one compound, deferasirox, is bona fide active site-binding inhibitor as shown by kinetic spectroscopic studies. Synthesis derivatives with...
Fe(II)- and 2-oxoglutarate (2OG)-dependent JumonjiC domain-containing histone demethylases (JmjC KDMs) are epigenetic eraser enzymes involved in the regulation of gene expression emerging drug targets oncology. We screened a set clinically used iron chelators report that they potently inhibit JMJD2A (KDM4A) vitro. Mode action investigations revealed one compound, deferasirox, is bona fide active site-binding inhibitor as shown by kinetic spectroscopic studies. Synthesis derivatives with...
Fe(II)- and 2-oxoglutarate (2OG)-dependent JumonjiC domain-containing histone demethylases (JmjC KDMs) are epigenetic eraser enzymes involved in the regulation of gene expression emerging drug targets oncology. We screened a set clinically used iron chelators report that they potently inhibit JMJD2A (KDM4A) vitro. Mode action investigations revealed one compound, deferasirox, is bona fide active site-binding inhibitor as shown by kinetic spectroscopic studies. Synthesis derivatives with...