Na, Yu-Ran Woo, Dustin J. Kim, So Yeon Yang, Eun Gyeong 2024-01-20T04:31:51Z 2024-01-20T04:31:51Z 2021-09-05 2016-04-01 0006-291X https://pubs.kist.re.kr/handle/201004/124182 Increasing evidence emphasizes the role of the hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) isoforms in regulating non-HIF substrates, but isoform selective PHD inhibitors under physiological conditions have not yet been reported. Here we have identified pyrithione Zn (PZ) as a potent, isoform-selective PHD3 inhibitor. The IC50 value of PZ was determined as 0.98 mu M for PHD3, while it did not show any inhibitory activity toward full length and truncated PHD2 up to 1 mM. The selective efficacy of PZ was further demonstrated at the cellular level by observing inhibition of the PHD3-dependent DNA damage response pathway without stabilization of HIF-1 alpha. (C) 2016 Elsevier Inc. All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE OXYGEN SENSOR HIF-ALPHA HIF-1-ALPHA UBIQUITYLATION METABOLISM PROMOTES SURVIVAL FAMILY Pyrithione Zn selectively inhibits hypoxia-inducible factor prolyl hydroxylase PHD3 Article 10.1016/j.bbrc.2016.02.115 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.472, no.2, pp.313 - 318 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 472 2 313 318 scie scopus 000373251300004 2-s2.0-84959498150 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article OXYGEN SENSOR HIF-ALPHA HIF-1-ALPHA UBIQUITYLATION METABOLISM PROMOTES SURVIVAL FAMILY Prolyl hydroxylase Pyrithione Zn Hypoxia-inducible factor Isoform selective inhibitor