Fast Responding Genes to HIF Prolyl Hydroxylase Inhibitors

Autor: Dmitry M. Hushpulian, Andrey A. Poloznikov, Sergey Nikulin, Irina G. Gazaryan, A. Yu. Khristichenko, T. A. Chubar
Rok vydání: 2021
Předmět:
Zdroj: Moscow University Chemistry Bulletin. 76:114-121
ISSN: 1935-0260
0027-1314
DOI: 10.3103/s002713142102005x
Popis: The attempts to elucidate the mechanism of the hypoxic activation of erythropoietin synthesis lead to the discovery of the hypoxia inducible factor (HIF) and its stability regulation via HIF prolyl hydroxylase, iron, and α-ketoglutarate dependent dioxygenase. Enzyme inhibitors mimic the action of hypoxia; however, they are far more specific. Comparative transcriptomic microanalysis of various types of the enzyme inhibitors versus hypoxia at short incubation times demonstrates the potency of inhibitors and points to the primary targets of HIF transcription factor. The power of inhibitors evaluated in the transcriptomic analysis matches the ranking of enzyme inhibitors based on the values of their half-activation constants in the HIF1 ODD-luc reporter assay. Neuradapt is 15–20 times more potent than roxadustat, and in addition, it is much more specific for the target enzyme than roxadustat and dimethyl oxalylglycine, which probably act also on other enzymes of the same family.
Databáze: OpenAIRE
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