Гены «быстрого» отклика при действии ингибиторов HIF пролилгидроксилазы

Вестник Московского университета. Серия 2: Химия. 2021. Т. 62. № 3. С. 213–222.

Хушпульян Д. М., Nikulin S., Христиченко А. Ю., Poloznikov A., Gazaryan I. G., Chubar T.

The attempts to elucidate the mechanism of hypoxic activation of erythropoietin synthesis let to the
discovery of 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, are
far more specific. Comparative transcriptomic microanalysis of various types on the enzyme inhibitors
with hypoxia at short incubation times demonstrates high 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 with respect to 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 are likely acting on
other enzymes of the same family.

Keywords: Gene expression, transcriptome, гипоксия, hypoxia, транкриптом, Neuradapt, Нейрадапт, roxadustat, роксадустат, dimethyl oxalylglycine, диметилоксалилглицин

Publication based on the results of: Разработка и валидация in vitro модели для оценки токсичности и проницаемости лекарственных препаратов через барьерную ткань тонкого кишечника в реальном времени (2022)