Erythropoetins in Therapy from the Point of View of a Medicinal Chemist

Hematopoietic growth factors are cytokines which stimulate growth of hematopoietic pluripotent stem cells and their differentiation and maturation into fully functional blood cells, either erythrocytes or various types of white blood cells. Erythropoietin is a glycosylated peptide hormone which stimulates production of red blood cells. It is used for treatment of anaemia caused by a chronic kidney failure. For therapeutic purposes, it is produced by recombinant technologies predominantly using modified mammalian cells. This procedure leads, however, to peptides of the same sequence of 165 amino acids but with different glycosylation patterns. These different mixtures of erythropoietin glycoforms have been designated with different INN names epoetin alfa - omega. Peginesatid (Omontys (R)) is a synthetic erythropoietin receptor agonist, the structure of which does not match that of erythropoietin. It is a pegylated covalent dimer of two identical peptide chains. It has been abandoned due to an increased mortality from cardiovascular reasons and due to dangerous allergies.