Prolyl hydroxylase domain-containing protein inhibitors as stabilizers of hypoxia-inducible factor: small molecule-based therapeutics for anemia
| Autor: | Lin Yan, Jeffrey J. Hale, Vincent J. Colandrea |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Hypoxia-Inducible Factor 1
Anemia Procollagen-Proline Dioxygenase Biology Patents as Topic Drug Delivery Systems Downregulation and upregulation hemic and lymphatic diseases Drug Discovery medicine Animals Humans Enzyme Inhibitors Pharmacology chemistry.chemical_classification Clinical Trials as Topic General Medicine Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Small molecule Enzyme Hypoxia-inducible factors chemistry Erythropoietin Drug Design Immunology Cancer research Erythropoiesis medicine.drug |
| Zdroj: | Expert Opinion on Therapeutic Patents. 20:1219-1245 |
| ISSN: | 1744-7674 1354-3776 |
| DOI: | 10.1517/13543776.2010.510836 |
| Popis: | Anemia caused by chronic kidney disease and other chronic diseases or conditions can be managed by the treatment of biologic-based erythropoiesis stimulating agents (ESAs). Although these ESAs are successful in treating these anemic conditions, a small molecule-based anti-anemia medicine can potentially revolutionize the treatment of anemia by bringing convenience to patients and being cost effective. Prolyl hydroxylase domain-containing protein (PHD) inhibitors may provide an opportunity for the development of small molecule anti-anemia medicines.This review covers efforts to target PHD enzymes for stabilization of hypoxia-inducible factor (HIF)-alpha subunits under normal oxygen levels as an attractive strategy to upregulate the expression of erythropoietin and genes involved in iron metabolism for the treatment of anemia.The reader will gain a brief summary of recent advances in HIF and PHD biology and a review of patents/patent applications on the subject of PHD inhibitors as HIF stabilizers for the treatment of anemia.Several classes of PHD enzyme inhibitors have been disclosed and several are currently in clinical trials for the development of small molecule-based therapeutics for the treatment of anemia. |
| Databáze: | OpenAIRE |
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