HIF prolyl hydroxylase inhibitors for anemia

被引：76
作者：
Muchnik, Eugene [1 ]
Kaplan, Joshua [1 ]
机构：
[1] Univ Med & Dent New Jersey, Newark, NJ 07103 USA
来源：
EXPERT OPINION ON INVESTIGATIONAL DRUGS | 2011年 / 20卷 / 05期
关键词：
anemia; anemia drug therapy; hypoxia-inducible factor; ischemia-reperfusion therapy; neoplasia drug therapy; oxygen physiology; prolyl hydroxylase; HYPOXIA-INDUCIBLE FACTORS; CHRONIC KIDNEY-DISEASE; ANKYRIN REPEAT DOMAIN; FACTOR-I; OXYGEN SENSOR; PHASE-I; TRANSCRIPTIONAL ACTIVATION; ASPARAGINYL HYDROXYLATION; ERYTHROPOIETIN GENE; PLATELET REACTIVITY;
D O I：
10.1517/13543784.2011.566861
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Introduction: The hypoxia-inducible factor (HIF) system mediates the body's response to hypoxia, locally, inducing angiogenesis and a shift to anaerobic metabolism, and systemically, increasing red cell mass in anemia. HIF prolyl hydroxylases (HIF-PH) modify HIF, decreasing its activity. Increasing HIF activity through inhibition of HIF-PH may provide an alternative treatment for anemia and may protect against damage related to ischemia-reperfusion. Areas covered: The review discusses the basic science underpinnings of the HIF system and the clinical effects of the HIF system and its pharmacologic manipulation. Expert opinion: Manipulation of the HIF system may improve outcomes in anemia by bypassing the effective iron deficiency found in anemia of chronic disease and by increasing red cell mass without supraphysiologic increases in erythropoietin. HIF-PH may also find a clinical use in the prevention of ischemia-reperfusion damage in strokes, cardiac ischemia, ischemic renal failure, etc.
引用
收藏
页码：645 / 656
页数：12
相关论文
共 115 条
  • [21] Asparaginyl hydroxylation of the notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor
    Coleman, Mathew L.
    McDonough, Michael A.
    Hewitson, Kirsty S.
    Coles, Charlotte
    Mecinovic, Jasmin
    Edelmann, Mariola
    Cook, Kristina M.
    Cockman, Matthew E.
    Lancaster, David E.
    Kessler, Benedikt M.
    Oldham, Neil J.
    Ratcliffe, Peter J.
    Schofield, Christopher J.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (33) : 24027 - 24038
  • [22] Normalization of hemoglobin level in patients with chronic kidney disease and anemia
    Drueke, Tilman B.
    Locatelli, Francesco
    Clyne, Naomi
    Eckardt, Kai-Uwe
    Macdougall, Iain C.
    Tsakiris, Dimitrios
    Burger, Hans-Ulrich
    Scherhag, Armin
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (20) : 2071 - 2084
  • [23] Studies on the activity of the hypoxia-inducible-factor hydroxylases using an oxygen consumption assay
    Ehrismann, Dominic
    Flashman, Emily
    Genn, David N.
    Mathioudakis, Nicolas
    Hewitson, Kirsty S.
    Ratcliffe, Peter J.
    Schofield, Christopher J.
    [J]. BIOCHEMICAL JOURNAL, 2007, 401 : 227 - 234
  • [24] CORRECTION OF THE ANEMIA OF END-STAGE RENAL-DISEASE WITH RECOMBINANT-HUMAN-ERYTHROPOIETIN - RESULTS OF A COMBINED PHASE-I AND PHASE-II CLINICAL-TRIAL
    ESCHBACH, JW
    EGRIE, JC
    DOWNING, MR
    BROWNE, JK
    ADAMSON, JW
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1987, 316 (02) : 73 - 78
  • [25] FARHA S, 2011, BLOOD
  • [26] Forsythe JA, 1996, MOL CELL BIOL, V16, P4604
  • [27] FROHNA PA, 2007, J AM SOC NEPHROL, V18, pA515
  • [28] HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells
    Fukuda, Ryo
    Zhang, Huafeng
    Kim, Jung-whan
    Shimoda, Larissa
    Dang, Chi V.
    Semenza, Gregg L.
    [J]. CELL, 2007, 129 (01) : 111 - 122
  • [29] Erythrocytosis-associated HIF-2α Mutations Demonstrate a Critical Role for Residues C-terminal to the Hydroxylacceptor Proline
    Furlow, Paul W.
    Percy, Melanie J.
    Sutherland, Scott
    Bierl, Charlene
    McMullin, Mary Frances
    Master, Stephen R.
    Lappin, Terence R. J.
    Lee, Frank S.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (14) : 9050 - 9058
  • [30] Autosomal dominant erythrocytosis and pulmonary arterial hypertension associated with an activating HIF2α mutation
    Gale, Daniel P.
    Harten, Sarah K.
    Reid, Cecil D. L.
    Tuddenham, Edward G. D.
    Maxwell, Patrick H.
    [J]. BLOOD, 2008, 112 (03) : 919 - 921
12345678910