Rapid degradation of hypoxia-inducible factor-1alpha by KRH102053, a new activator of prolyl hydroxylase 2.

ABSTRACT:

Background and purpose

Hypoxia-inducible factor (HIF) is a transcription factor induced by hypoxia and degraded by ubiquitin-dependent proteasomes in normoxic conditions. Under hypoxic conditions, hydroxylation of HIF-1alpha subunit by prolyl hydroxylase (PHD) is suppressed, thus leading to increased levels of HIF. Although PHD2 plays a key role in regulating the levels of HIF, chemical activators of PHD2 are relatively unknown. The aim of this study was to identify small molecule activators of PHD2 that could be used, eventually, to suppress the level of HIF-1alpha.

Experimental approach

By using the overproduced PHD2 as a target, a molecular library consisting of more than 600 small molecules with a benzopyran structure was screened with an HPLC assay method.

Key result

SUBMITTER: Choi HJ 

PROVIDER: S-EPMC2438970 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature