|Systematic (IUPAC) name|
|1-((1S,3aR,14bS)-2-Methoxy-1,5,6,8,9,14b-hexahydro-4H-cyclopenta(a)(1,3)dioxolo(4,5-h)pyrrolo(2,1-b)(3)benzazepin-1-yl) 4-methyl (2R)-2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate|
|Licence data||US FDA:|
|Pregnancy cat.||D (US)|
|Legal status||℞-only (US)|
|Routes||Subcutaneous, intravenous infusion|
|Metabolism||Mostly via plasma esterases|
|Excretion||Urine (≤15% unchanged)|
|Mol. mass||545.62 g/mol|
Omacetaxine mepesuccinate (INN, trade name Synribo) is a pharmaceutical drug that is indicated for treatment of chronic myelogenous leukemia (CML). It is a semi-synthetic derivative of the alkaloid cephalotaxine from Cephalotaxus harringtonia. It was approved by the US FDA in October 2012 for the treatment of adult patients with CML with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs).
In June 2009, results of a long-term open label Phase II study were published, which investigated the use of omacetaxine infusions in CML patients. After twelve months of treatment, about one third of patients showed a cytogenetic response. A study in patients who had failed imatinib and who had the drug resistant T315I mutation achieved cytogenetic response in 28% of patients and haematological response in 80% of patients, according to preliminary data.
Phase I studies including a small number of patients have shown benefit in treating myelodysplastic syndrome (MDS, 25 patients) and acute myelogenous leukaemia (AML, 76 patients). Patients with solid tumors did not benefit from omacetaxine.
Common (1-10% frequency):
- GI haemorrhages
Mechanism of action
Omacetaxine is a protein translation inhibitor. It inhibits protein translation by preventing the initial elongation step of protein synthesis. It interacts with the ribosomal A-site and prevents the correct positioning of amino acid side chains of incoming aminoacyl-tRNAs. Omacetaxine acts only on the initial step of protein translation and does not inhibit protein synthesis from mRNAs that have already commenced translation.
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