title: Recent Advances in Developing Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylases and Their Therapeutic Implications.
abstract: Hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs) are members of the 2-oxoglutarate dependent non-heme iron dioxygenases. Due to their physiological roles in regulation of HIF-1α stability, many efforts have been focused on searching for selective PHD inhibitors to control HIF-1α levels for therapeutic applications. In this review, we first describe the structure of PHD2 as a molecular basis for structure-based drug design (SBDD) and various experimental methods developed for measuring PHD activity. We further discuss the current status of the development of PHD inhibitors enabled by combining SBDD approaches with high-throughput screening. Finally, we highlight the clinical implications of small molecule PHD inhibitors.
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Korea. soyeonkim@kist.re.kr.|Department of Biomedical Engineering, Korea University of Science and Technology (UST), KIST campus, Seoul 136-791, Korea. soyeonkim@kist.re.kr.
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Korea. eunyang@kist.re.kr.|Department of Biological Chemistry, Korea University of Science and Technology (UST), KIST campus, Seoul 136-791, Korea. eunyang@kist.re.kr.
authors.forename: Eun Gyeong
authors.initials: EG
authors.lastname: Yang
mesh_terms: D000740:Anemia / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D055808:Drug Discovery / Q000379:methods; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D057166:High-Throughput Screening Assays; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism; D008968:Molecular Conformation; D064828:Prolyl Hydroxylases / Q000737:chemistry / Q000378:metabolism*; D064800:Prolyl-Hydroxylase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D013329:Structure-Activity Relationship
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D064800:Prolyl-Hydroxylase Inhibitors; D064828:Prolyl Hydroxylases
keywords: high-throughput screening (HTS); hypoxia-inducible factor (HIF); prolyl hydroxylase (PHD) inhibitor; structure-based drug design (SBDD)