Idrugs
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Homoharringtonine (HHT), a natural alkaloid extracted from various Cephalotaxus species, exerts its antitumoral and anti-angiogenic activity through an inhibition of protein synthesis and the promotion of apoptosis. ChemGenex Pharmaceuticals Ltd, in collaboration with Stragen Group, is developing omacetaxine mepesuccinate, a semisynthetic formulation of HHT, as a potential treatment for chronic myelocytic leukemia (CML), myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). In preclinical studies, omacetaxine mepesuccinate induced apoptosis in leukemia cell lines. ⋯ Phase II and III clinical trials are underway to assess the activity of omacetaxine mepesuccinate, either alone or in combination with TKIs or other cytotoxic drugs, in patients with CML that is resistant to TKI therapy. Phase I and II clinical trials for omacetaxine mepesuccinate in the treatment of AML and MDS are also ongoing; intravenous, subcutaneous and oral formulations of the drug are being developed. Omacetaxine mepesuccinate appears to hold potential for the treatment of CML and, in particular, imatinib-resistant CML; the development of alternative formulations of the therapeutic further expands the potential for success in drug development.