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      Development and characterization of novel erythropoiesis stimulating protein (NESP)

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          Abstract

          Studies on human erythropoietin (EPO) demonstrated that there is a direct relationship between the sialic acid-containing carbohydrate content of the molecule and its serum half-life and in vivo biological activity, but an inverse relationship with its receptor-binding affinity. These observations led to the hypothesis that increasing the carbohydrate content, beyond that found naturally, would lead to a molecule with enhanced biological activity. Hyperglycosylated recombinant human EPO (rHuEPO) analogues were developed to test this hypothesis. Darbepoetin alfa (novel erythropoiesis stimulating protein, NESP, ARANESP TM, Amgen Inc, Thousand Oaks, CA), which was engineered to contain 5 N-linked carbohydrate chains (two more than rHuEPO), has been evaluated in preclinical animal studies. Due to its increased sialic acid-containing carbohydrate content, NESP is biochemically distinct from rHuEPO, having an increased molecular weight and greater negative charge. Compared with rHuEPO, it has an approximate 3-fold longer serum half-life, greater in vivo potency, and can be administered less frequently to obtain the same biological response. NESP is currently being evaluated in human clinical trials for treatment of anaemia and reduction in its incidence.© 2001 Cance Cance Cancer Research Campaign

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          Author and article information

          Journal
          Br J Cancer
          British Journal of Cancer
          Nature Publishing Group
          0007-0920
          1532-1827
          April 2001
          : 84
          : S1
          : 3-10
          Affiliations
          [1 ]Amgen Inc, One Amgen Center Drive, MS 27-4-A, Thousand Oaks, CA 91320-799, USA
          Article
          6691746
          10.1054/bjoc.2001.1746
          2363897
          11308268
          31ca6799-c3b7-4c1e-8c95-9ff521d6c1ec
          Copyright 2001, Cancer Research Campaign
          History
          Categories
          Regular Article

          Oncology & Radiotherapy
          biological activity,erythropoietin,darbepoetin alfa,pharmacokinetics,carbohydrate,review

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