Omacetaxine mepesuccinate
 |
|
|---|---|
| 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 | |
| Clinical data | |
| Pregnancy cat. | ? |
| Legal status | ? |
| Routes | Subcutaneous, intravenous infusion |
| Identifiers | |
| CAS number | 26833-87-4 |
| ATC code | L01XX40 |
| PubChem | CID 285033 |
| UNII | 6FG8041S5B  |
| ChEBI | CHEBI:71019 |
| Chemical data | |
| Formula | C29H39NO9 |
| Mol. mass | 545.62 g/mol |
|
|
|
|
Omacetaxine mepesuccinate (INN, or homoharringtonine, trade name Synribo) is an alkaloid from Cephalotaxus harringtonia that is indicated for treatment of Chronic Myelogenous Leukemia. It was approved by the USFDA on 26th October 2012 for the treatment of adult patients with chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs).[1]
Contents |
Mechanism of action [edit]
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.[2]
Uses [edit]
Omacetaxine has been approved for the treatment of adult patients of CML who show resistance and/or intolerance to two or more tyrosine kinase inhibitors. Omacetaxine can be used in both the chronic phase and the accelerated phase of CML. Administered subcutaneously, omacetaxine is to be dosed twice daily for 14 consecutive days of a 28-day cycle at treatment induction, and twice daily for seven consecutive days of a 28-day cycle during maintenance therapy once a response is achieved.[3]
Adverse Drug Reactions [edit]
Most common adverse reactions (frequency ≥20%) in chronic and accelerated phase patients include thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia. [4]
Studies [edit]
In vitro and animal model trials showed that omacetaxine has potential to treat resistant leukemia mainly chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL).[5]
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.[6] A study in patients who had failed imatinib and who had the drug resistant T315I mutation achieved cytogenetic response in 28% of patients and hematological response in 80% of patients, according to preliminary data.[7]
Phase I studies including a small number of patients have shown benefit in treating myelodysplastic syndrome (MDS, 25 patients)[8] and acute myelogenous leukemia (AML, 76 patients).[9] Patients with solid tumors did not benefit from omacetaxine.[10]
References [edit]
- ^ http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm325895.htm.
- ^ Wetzler M, Segal D. Omacetaxine as an Anticancer Therapeutic: What is Old is New Again. Current Pharmaceutical Design 2011;17:59-64
- ^ http://www.heraldonline.com/2012/10/26/4367848/teva-receives-approval-for-synribotm.html
- ^ http://www.heraldonline.com/2012/10/26/4367848/teva-receives-approval-for-synribotm.html
- ^ Will Boggs (April 14, 2009). "Omacetaxine has potential to treat resistant leukemia". Reuters.
- ^ Li, Y. F.; Deng, Z. K.; Xuan, H. B.; Zhu, J. B.; Ding, B. H.; Liu, X. N.; Chen, B. A. (2009). "Prolonged chronic phase in chronic myelogenous leukemia after homoharringtonine therapy". Chinese medical journal 122 (12): 1413–1417. PMID 19567163.
- ^ Quintás-Cardama, A.; Kantarjian, H.; Cortes, J. (2009). "Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009". Cancer 115 (23): 5382–5393. doi:10.1002/cncr.24601. PMID 19739234.
- ^ Wu, L.; Li, X.; Su, J.; Chang, C.; He, Q.; Zhang, X.; Xu, L.; Song, L. et al. (2009). "Effect of low-dose cytarabine, homoharringtonine and granulocyte colony-stimulating factor priming regimen on patients with advanced myelodysplastic syndrome or acute myeloid leukemia transformed from myelodysplastic syndrome". Leukemia & Lymphoma 50 (9): 1461. doi:10.1080/10428190903096719.
- ^ Gu, L. F.; Zhang, W. G.; Wang, F. X.; Cao, X. M.; Chen, Y. X.; He, A. L.; Liu, J.; Ma, X. R. (2010). "Low dose of homoharringtonine and cytarabine combined with granulocyte colony-stimulating factor priming on the outcome of relapsed or refractory acute myeloid leukemia". Journal of Cancer Research and Clinical Oncology 137 (6): 997–1003. doi:10.1007/s00432-010-0947-z. PMID 21152934.
- ^ Kantarjian, H. M.; Talpaz, M.; Santini, V.; Murgo, A.; Cheson, B.; O'Brien, S. M. (2001). "Homoharringtonine". Cancer 92 (6): 1591–1605. doi:10.1002/1097-0142(20010915)92:6<1591::AID-CNCR1485>3.0.CO;2-U. PMID 11745238.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
This antineoplastic or immunomodulatory drug article is a stub. You can help Wikipedia by expanding it. |
