Prolyl Hydroxylase Inhibitors: A Breakthrough in the Therapy of Anemia Associated with Chronic Diseases

被引：142

作者：

Joharapurkar, Amit A. ^{[1
]}

Pandya, Vrajesh B. ^{[1
]}

Patel, Vishal J. ^{[1
]}

Desai, Ranjit C. ^{[1
]}

Jain, Mukul R. ^{[1
]}

机构：

[1] Cadila Healthcare Ltd, Zydus Res Ctr, Sarkhej Bavla NH8A, Ahmadabad 382210, Gujarat, India

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 61卷 / 16期

关键词：

HYPOXIA-INDUCIBLE FACTOR; CHRONIC KIDNEY-DISEASE; FACTOR-I HIF-1; ERYTHROPOIETIN PRODUCTION; CRYSTAL-STRUCTURE; IRON-DEFICIENCY; CLINICAL-TRIAL; RENAL ANEMIA; PHASE-I; DOMAIN;

D O I：

10.1021/acs.jmedchem.7b01686

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Chronic kidney disease, cancer, chronic inflammatory disorders, nutritional, and genetic deficiency can cause anemia. Hypoxia causes induction of hypoxia-inducible factor (HIF), which stimulates erythropoietin (EPO) synthesis. Prolyl hydroxylase domain (PHD) enzyme inhibition can stabilize hypoxia-inducible factor (HIF). HIF stabilization also decreases hepcidin, a hormone of hepatic origin, which regulates iron homeostasis. PHD inhibitors represent a novel pharmacological treatment of anemia associated with chronic diseases. Many orally active PHD inhibitors like roxadustat, molidustat, vadadustat, and desidustat are in late phase clinical trials. This review discusses the role of PHD inhibitors in the treatment of anemia associated with chronic diseases.

引用

页码：6964 / 6982

页数：19

共 138 条

[1] 1,2,4-Triazolo-[1,5-a]pyridine HIF Prolylhydroxylase Domain-1 (PHD-1) Inhibitors With a Novel Monodentate Binding Interaction [J].

Ahmed, Saleh ;

Ayscough, Andrew ;

Barker, Greg R. ;

Canning, Hannah E. ;

Davenport, Richard ;

Downham, Robert ;

Harrison, David ;

Jenkins, Kerry ;

Kinsella, Natasha ;

Livermore, David G. ;

Wright, Susanne ;

Ivetac, Anthony D. ;

Skene, Robert ;

Wilkens, Steven J. ;

Webster, Natalie A. ;

Hendrick, Alan G. .

JOURNAL OF MEDICINAL CHEMISTRY, 2017, 60 (13) :5663-5672

[2] Effects of Daprodustat, a Novel Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Anemia Management in Japanese Hemodialysis Subjects [J].

Akizawa, Tadao ;

Tsubakihara, Yoshiharu ;

Nangaku, Masaomi ;

Endo, Yukihiro ;

Nakajima, Hiromu ;

Kohno, Tomoko ;

Imai, Yukiko ;

Kawase, Natsumi ;

Hara, Katsutoshi ;

Lepore, John ;

Cobitz, Alexander .

AMERICAN JOURNAL OF NEPHROLOGY, 2017, 45 (02) :127-135

[3] Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism [J].

Aragones, Julian ;

Schneider, Martin ;

Van Geyte, Katie ;

Fraisl, Peter ;

Dresselaers, Tom ;

Mazzone, Massimiliano ;

Dirkx, Ruud ;

Zacchigna, Serena ;

Lemieux, Helene ;

Jeoung, Nam Ho ;

Lambrechts, Diether ;

Bishop, Tammie ;

Lafuste, Peggy ;

Diez-Juan, Antonio ;

Harten, Sarah K. ;

Van Noten, Pieter ;

De Bock, Katrien ;

Willam, Carsten ;

Tjwa, Marc ;

Grosfeld, Alexandra ;

Navet, Rachel ;

Moons, Lieve ;

Vandendriessche, Thierry ;

Deroose, Christophe ;

Wijeyekoon, Bhathiya ;

Nuyts, Johan ;

Jordan, Benedicte ;

Silasi-Mansat, Robert ;

Lupu, Florea ;

Dewerchin, Mieke ;

Pugh, Chris ;

Salmon, Phil ;

Mortelmans, Luc ;

Gallez, Bernard ;

Gorus, Frans ;

Buyse, Johan ;

Sluse, Francis ;

Harris, Robert A. ;

Gnaiger, Erich ;

Hespel, Peter ;

Van Hecke, Paul ;

Schuit, Frans ;

Van Veldhoven, Paul ;

Ratcliffe, Peter ;

Baes, Myriam ;

Maxwell, Patrick ;

Carmeliet, Peter .

NATURE GENETICS, 2008, 40 (02) :170-180

[4]

AREND MP, 2004, Patent No. 2004108681

[5] Discovery and Preclinical Characterization of GSK1278863 (Daprodustat), a Small Molecule Hypoxia Inducible Factor-Prolyl Hydroxylase Inhibitor for Anemias [J].

Ariazi, Jennifer L. ;

Duffy, Kevin J. ;

Adams, David F. ;

Fitch, Duke M. ;

Luo, Lusong ;

Pappalardi, Melissa ;

Biju, Mangatt ;

DiFilippo, Erin Hugger ;

Shaw, Tony ;

Wiggall, Ken ;

Erickson-Miller, Connie .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2017, 363 (03) :336-347

[6] INHIBITION OF PROLYL 4-HYDROXYLASE BY OXALYL AMINO-ACID DERIVATIVES IN-VITRO, IN ISOLATED MICROSOMES AND IN EMBRYONIC CHICKEN TISSUES [J].

BAADER, E ;

TSCHANK, G ;

BARINGHAUS, KH ;

BURGHARD, H ;

GUNZLER, V .

BIOCHEMICAL JOURNAL, 1994, 300 :525-530

[7] Mechanisms of Anemia in CKD [J].

Babitt, Jodie L. ;

Lin, Herbert Y. .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2012, 23 (10) :1631-1634

[8] BLUNTED ERYTHROPOIETIN RESPONSE TO ANEMIA IN RHEUMATOID-ARTHRITIS [J].

BAER, AN ;

DESSYPRIS, EN ;

GOLDWASSER, E ;

KRANTZ, SB .

BRITISH JOURNAL OF HAEMATOLOGY, 1987, 66 (04) :559-564

[9] Prolyl hydroxylase inhibition corrects functional iron deficiency and inflammation-induced anaemia in rats [J].

Barrett, Terrance D. ;

Palomino, Heather L. ;

Brondstetter, Theresa I. ;

Kanelakis, Kimon C. ;

Wu, Xiaodong ;

Yan, Wen ;

Merton, Katherine P. ;

Schoetens, Freddy ;

Ma, Jing Ying ;

Skaptason, Judy ;

Gao, Jingjin ;

Da-Thao Tran ;

Venkatesan, Hariharan ;

Rosen, Mark D. ;

Shankley, Nigel P. ;

Rabinowitz, Michael H. .

BRITISH JOURNAL OF PHARMACOLOGY, 2015, 172 (16) :4078-4088

[10] Pharmacological Characterization of 1-(5-Chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic Acid (JNJ-42041935), a Potent and Selective Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor [J].

Barrett, Terrance D. ;

Palomino, Heather L. ;

Brondstetter, Theresa I. ;

Kanelakis, Kimon C. ;

Wu, Xiaodong ;

Haug, Peter V. ;

Yan, Wen ;

Young, Andrew ;

Hua, Hong ;

Hart, Juliet C. ;

Da-Thao Tran ;

Venkatesan, Hariharan ;

Rosen, Mark D. ;

Peltier, Hillary M. ;

Sepassi, Kia ;

Rizzolio, Michele C. ;

Bembenek, Scott D. ;

Mirzadegan, Tara ;

Rabinowitz, Michael H. ;

Shankley, Nigel P. .

MOLECULAR PHARMACOLOGY, 2011, 79 (06) :910-920

← 1 2 3 4 5 6 7 8 9 10 →