Tosedostat for the treatment of relapsed and refractory acute myeloid leukemia

Courtney D. Dinardo, Jorge E. Cortes

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Introduction: Despite recent improvements in the scientific understanding of leukemia biology, the overall prognosis for adults with acute myeloid leukemia (AML) remains disappointingly poor. Therapeutic options for AML that are relapsed or refractory to front-line chemotherapy are limited, and the development of effective agents for this indication is an unmet need. The aminopeptidase-inhibitor tosedostat (CHR-2797) is a novel metalloenzyme inhibitor that blocks a critical step in the protein degradation and re-synthesizes intracellular pathway. This orally bioavailable agent has shown promising activity in vitro and in early clinical trials for patients with relapsed/refractory AML. Areas covered: This review summarizes the development of tosedostat to date. Specifically, the authors review the literature on its mechanism of action, pharmacoepidemiology and the currently available preclinical and clinical data. Expert opinion: Tosedostat is an oral agent with a novel mechanism of action. Early trials of tosedostat in relapsed/refractory elderly AML have shown encouraging results in a population with an overall very poor prognosis. This is particularly noted in patients with a prior history of myelodysplastic syndrome (MDS) and hypomethylating-agent (HMA) use. Additional studies of tosedostat in rationally designed combinations with cytarabine and HMAs in advanced MDS and refractory AML populations are ongoing. Furthermore, the safety and efficacy evaluation is similarly ongoing, and patient selection will be an important consideration in the continued development of this promising compound.

Original languageEnglish (US)
Pages (from-to)265-272
Number of pages8
JournalExpert Opinion on Investigational Drugs
Issue number2
StatePublished - Feb 2014
Externally publishedYes


  • Acute myeloid leukemia
  • Aminopeptidase inhibitor
  • Drug development
  • Tosedostat

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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