JNJ 42041935 is a potent, 2-oxoglutarate competitive, reversible, and selective inhibitor of PHD enzymes. Administration of JNJ-42041935 to rats for 5 consecutive days resulted in a 2-fold increase in reticulocytes, an increase in hemoglobin, and an increase in the hematocrit. It may be an effective means to treat anemia of various origin, in which current treatments are ineffective or not optimal.

Daprodustat (DUVROQ) is a small molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (PHD) developed by GlaxoSmithKline for the treatment of anaemia in patients with chronic kidney disease (CKD). Inhibition of PHD prevents degradation of hypoxia-inducible factor (HIF), leading to the production of erythropoietin and subsequent induction of erythropoiesis. In June, daprodustat received its first approval in Japan for the treatment of renal anaemia.

Molidustat also was known as BAY 85-3934 is a novel inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) which stimulates erythropoietin (EPO) production and the formation of red blood cells. Hypoxia-inducible factor (HIF) is the major transcription factor involved in erythropoietin gene expression. Because oxygen-dependent degradation of the α subunit of HIF suppresses erythropoietin expression, stimulation of erythropoiesis by agents that prevent degradation of HIF has been one strategy for managing anemia. Thus, molidustat is in phase II of a clinical trial to investigate the effects therapy in patients with renal anemia associated with chronic kidney disease and/or end-stage renal disease.

Roxadustat (FG-4592) is an HIF α prolyl hydroxylase inhibitor in a cell-free assay. It stabilizes HIF-2 and induces EPO production and stimulates erythropoiesis. Roxadustat transiently and moderately increased endogenous erythropoietin and reduced hepcidin. It is currently being investigated as an oral treatment for anemia associated with chronic kidney disease (CKD). In April 2006, Roxadustat (FG-4592) was licensed to Astellas Pharma by originator FibroGen in Asia, Europe and South Africa for the treatment of anemia. FibroGen retains rights in the rest of the world. In 2007, the FDA put the trial on clinical hold due to one case of death by fulminant hepatitis during a phase II clinical trial for patients with anemia associated with chronic kidney disease and not requiring dialysis. However, in 2008, the FDA informed the company that clinical trials could be resumed. Phase II/III clinical trials for this indication resumed in 2012. In 2013, the compound was licensed to AstraZeneca by FibroGen for development and marketing in US, CN and all major markets excluding JP, Europe, the Commonwealth of Independent States, the Middle East and South Africa, for the treatment of anemia associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD).

Molidustat also was known as BAY 85-3934 is a novel inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) which stimulates erythropoietin (EPO) production and the formation of red blood cells. Hypoxia-inducible factor (HIF) is the major transcription factor involved in erythropoietin gene expression. Because oxygen-dependent degradation of the α subunit of HIF suppresses erythropoietin expression, stimulation of erythropoiesis by agents that prevent degradation of HIF has been one strategy for managing anemia. Thus, molidustat is in phase II of a clinical trial to investigate the effects therapy in patients with renal anemia associated with chronic kidney disease and/or end-stage renal disease.

Roxadustat (FG-4592) is an HIF α prolyl hydroxylase inhibitor in a cell-free assay. It stabilizes HIF-2 and induces EPO production and stimulates erythropoiesis. Roxadustat transiently and moderately increased endogenous erythropoietin and reduced hepcidin. It is currently being investigated as an oral treatment for anemia associated with chronic kidney disease (CKD). In April 2006, Roxadustat (FG-4592) was licensed to Astellas Pharma by originator FibroGen in Asia, Europe and South Africa for the treatment of anemia. FibroGen retains rights in the rest of the world. In 2007, the FDA put the trial on clinical hold due to one case of death by fulminant hepatitis during a phase II clinical trial for patients with anemia associated with chronic kidney disease and not requiring dialysis. However, in 2008, the FDA informed the company that clinical trials could be resumed. Phase II/III clinical trials for this indication resumed in 2012. In 2013, the compound was licensed to AstraZeneca by FibroGen for development and marketing in US, CN and all major markets excluding JP, Europe, the Commonwealth of Independent States, the Middle East and South Africa, for the treatment of anemia associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD).