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

被引：127

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

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