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Omacetaxine mepesuccinate

Omacetaxine mepesuccinate is a semisynthetic derivative of the cytotoxic plant alkaloid homoharringtonine isolated from the evergreen tree Cephalotaxus with potential antineoplastic activity. Omacetaxine mepesuccinate binds to the 80S ribosome in eukaryotic cells and inhibits protein synthesis by interfering with chain elongation. This agent also induces differentiation and apoptosis in some cancer cell types. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Omacetaxine mepesuccinate is administered subcutaneously and acts differently from TKIs. It may have a therapeutic advantage for patients who have failed TKIs. Omacetaxine is currently in global phase 2/3 clinical trials for CML and has been granted Orphan Drug designations by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMEA) as well as Fast Track status by the FDA. In vitro and animal model trails are promising and recent results showed that omacetaxine has potential to treat resistant leukemia mainly CML and ALL.

Current developer:  ChemGenex Pharmaceuticals Limited

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5: Meng HT, Li L, Liu H, Wang Y, Li GC, Qian WB. Homoharringtonine acts synergistically with SG235-TRAIL, a conditionally replicating adenovirus, in human leukemia cell lines. Acta Pharmacol Sin. 2009 Nov;30(11):1529-36. Epub 2009 Oct 12. PubMed PMID: 19820719.

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7: Quintás-Cardama A, Kantarjian H, Cortes J. Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009. Cancer. 2009 Dec 1;115(23):5382-93. Review. PubMed PMID: 19739234.

8: Li YF, Deng ZK, Xuan HB, Zhu JB, Ding BH, Liu XN, Chen BA. Prolonged chronic phase in chronic myelogenous leukemia after homoharringtonine therapy. Chin Med J (Engl). 2009 Jun 20;122(12):1413-7. PubMed PMID: 19567163.

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10: Chen Y, Hu Y, Michaels S, Segal D, Brown D, Li S. Inhibitory effects of omacetaxine on leukemic stem cells and BCR-ABL-induced chronic myeloid leukemia and acute lymphoblastic leukemia in mice. Leukemia. 2009 Aug;23(8):1446-54. Epub 2009 Mar 26. PubMed PMID: 19322212; PubMed Central PMCID: PMC2726272.

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39: Legros L, Hayette S, Nicolini FE, Raynaud S, Chabane K, Magaud JP, Cassuto JP, Michallet M. BCR-ABL(T315I) transcript disappearance in an imatinib-resistant CML patient treated with homoharringtonine: a new therapeutic challenge? Leukemia. 2007 Oct;21(10):2204-6. Epub 2007 May 31. PubMed PMID: 17541396.

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