title: New thrombopoietin receptor agonists for platelet disorders.
abstract: Since thrombopoietin (TPO) was cloned in 1994, TPO receptor (TPO-R) agonists have been developed which have shown significant clinical activity in various conditions characterized by thrombocytopenia. First-generation TPO-R agonists were recombinant forms of human TPO. The clinical development of these molecules was discontinued after one of them, pegylated recombinant human megakaryocyte growth and development factor, was associated with the development of neutralizing autoantibodies cross-reacting with endogenous TPO. Second-generation TPO-R agonists are now available, which present no sequence homology to endogenous TPO. Two of these new agents, romiplostim and eltrombopag, have been granted marketing authorization for use in patients with primary immune thrombocytopenia unresponsive to conventional treatments. Clinical trials with TPO-R agonists are also ongoing in other thrombocytopenias, such as hepatitis C virus-related thrombocytopenia and the myelodysplastic syndromes.
authors.affiliation: Department of Haematology, St. George's Hospital, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Homeida
authors.forename: C
authors.initials: C
authors.lastname: Ebdon
authors.forename: P
authors.initials: P
authors.lastname: Batty
authors.forename: B
authors.initials: B
authors.lastname: Jackson
authors.forename: S
authors.initials: S
authors.lastname: Kolade
authors.forename: C
authors.initials: C
authors.lastname: Bateman
authors.forename: Y Y
authors.initials: YY
authors.lastname: Peng
authors.forename: R
authors.initials: R
authors.lastname: Stasi
mesh_terms: D000818:Animals; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D001791:Blood Platelet Disorders / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D019317:Evidence-Based Medicine; D006801:Humans; D006834:Hydrazines / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011961:Receptors, Fc / Q000627:therapeutic use*; D053628:Receptors, Thrombopoietin / Q000819:agonists* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D013926:Thrombopoietin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; C082218:MPL protein, human; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag