Hematopoietic growth factor mimetics: from concept to clinic.
Hematopoietic growth factor (HGF) mimetics offer a number of attractive advantages as therapeutic agents. Small chemical compounds, in particular, provide reduced cost and oral availability. As many of these mimetics are unrelated in structure to the normal cytokine the immunogenic response is not a significant issue. Isolation of small peptide agonists for erythropoietin (EPO) and thrombopoietin (TPO) receptors has been associated with significant translational challenges and here we summarize approaches used to achieve the potency and stability required for clinical utility. We also compare and contrast the initial screening approaches, and the translational and clinical issues associated with two recently approved TPO mimetics, romiplostim and the orally available eltrombopag. Finally we summarize the development and clinical findings for the EPO mimetic, Hematide, consider alternative approaches, and discuss the future potential for isolation of growth factor (GF) mimetics.
Perugini
Michelle
M
Hanson Institute and SA Pathology, Adelaide, South Australia, Australia. Michelle.Perugini@imvs.sa.gov.au
Varelias
Antiopi
A
Sadlon
Timothy
T
D'Andrea
Richard J
RJ
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016207:Cytokines / Q000737:chemistry; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D016298:Hematopoietic Cell Growth Factors / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy; D017467:Receptors, Erythropoietin / Q000819:agonists; D011961:Receptors, Fc / Q000737:chemistry; D053628:Receptors, Thrombopoietin / Q000819:agonists; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin
D002352:Carrier Proteins; D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D010455:Peptides; D017467:Receptors, Erythropoietin; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; C514771:hematide; D011092:Polyethylene Glycols; D013926:Thrombopoietin; C488777:romiplostim