Omacetaxine mepesuccinate for the treatment of leukemia

Kim, Theo Daniel; Frick, Mareike; Coutre, Philipp le

doi:10.1517/14656566.2011.613378

Cited by 15 publications

(9 citation statements)

References 68 publications

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“…For example, in imatinib-resistant K562 cells, omacetaxine mepesuccinate caused degradation of BCR-ABL proteins by inhibiting heat shock protein 90 in a dose-dependent manner which mediates the resistance of BCR-ABL-expressing cells to apoptosis. Omacetaxine mepesuccinate also had a similar inhibitory effect on BCR-ABL T315I expressing leukemia stem cells [70,72] which is resistant to TKIs except ponatinib [64].…”

Section: Semi-synthetic Productmentioning

confidence: 84%

“…HHT is a natural cephalotaxine alkaloid originally derived from the bark of several cephalotaxus species that are indigenous to Asia (mostly mainland China, and also Japan, Korea, and India). Historically, extracts from the bark of cephalotaxus were used in cancer patients by practitioners of traditional Chinese medicine in the Fujian Province of China [70,71].…”

Section: Semi-synthetic Productmentioning

confidence: 99%

“…But the mechanism for the antileukemic effect of omacetaxine mepesuccinate is mainly related to induction of apoptosis in leukemia cells [70]. It has also demonstrated activity against TKIresistant BCR-ABL mutations since it acts independently of BCR-ABL kinase-binding activity.…”

Section: Semi-synthetic Productmentioning

confidence: 99%

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Current Management Approaches of Chronic Myeloid Leukemia

Fentie¹,

Woldu²

2017

J Cancer Sci Ther

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Chronic myeloid leukemia is a slowly progressive and clonal myeloproliferative disorder characterized by the presence of Philadelphia chromosome. Even if the global incidence is unknown, CML accounts for 15% to 20% cases of adult leukemia's in USA and is predominantly the disease of adults. It has three phases reflecting the grade of malignancy; chronic phase, accelerated phase and blast crisis phase. Initial diagnosis and monitoring of treatment response is based on hematologic, cytogenetic and molecular assessments that need to be regularly checked. The treatment in each phase had undergone a profound progress over a relatively short period of time, starting with arsenic therapy, radiotherapy, allogeneic hematopoietic stem cell transplantation, recombinant interferon-alfa, busulfan, and hydroxyurea, and more recently with the tyrosine kinase inhibitors. Among tyrosine kinase inhibitors national comprehensive cancer network puts imatinib, dastinib and nilotinib as category 1 recommendation for initial treatment of chronic phase chronic myeloid leukemia. Second generation tyrosine kinase inhibitors; nilotinib, dasatinib, bosutinib and ponatinib had shown inducing higher rates of early optimal responses, although their impact on long-term overall survival remains to be determined. There are also drugs for the treatment of chronic myeloid leukemia such as histone deacetylase inhibitors, proteasome inhibitors and farnesyl transferase inhibitors which are under investigation. In addition to these vaccines are under investigation as a part of treatment for chronic myeloid leukemia which still needs further research.

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Section: Semi-synthetic Productmentioning

confidence: 84%

Section: Semi-synthetic Productmentioning

confidence: 99%

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Current Management Approaches of Chronic Myeloid Leukemia

Fentie¹,

Woldu²

2017

J Cancer Sci Ther

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“…It is a natural cephalotaxine alkaloid (Figure 1), and is originally derived from the bark of several cephalotaxus species that are indigenous to Asia (mostly mainland China, and also Japan, Korea, and India) 40. The molecular weight of omacetaxine mepesuccinate is 545.62 (g/mol) 40. Historically, extracts from the bark of cephalotaxus were used in cancer patients by practitioners of traditional Chinese medicine in the Fujian Province of China 41.…”

Section: Pharmacology Mode Of Action and Pharmacokineticsmentioning

confidence: 99%

Omacetaxine mepesuccinate in the treatment of intractable chronic myeloid leukemia

Chen¹,

Li²

2014

OTT

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In a significant proportion of patients with chronic myeloid leukemia, resistance to BCR-ABL tyrosine kinase inhibitors develops due to acquisition of BCR-ABL kinase domain mutations and insensitivity of leukemia stem cells to tyrosine kinase inhibitors. Omacetaxine mepesuccinate (formerly called homoharringtonine) is a natural alkaloid that inhibits protein synthesis and induces cell death. Omacetaxine mepesuccinate has been recently approved by the US Food and Drug Administration to treat patients with chronic myeloid leukemia who failed to respond to multiple tyrosine kinase inhibitors and/or acquired the BCR-ABL-T315I mutation. In this review, we discuss the use and effectiveness of omacetaxine mepesuccinate in the treatment of chronic myeloid leukemia, with coverage of its pharmacology, mode of action, and pharmacokinetics. We believe that omacetaxine mepesuccinate will be beneficial to many patients with chronic myeloid leukemia who do not respond well to tyrosine kinase inhibitors.

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“…Even with these apparent limitations, there has been renewed interest in using translation elongation inhibitors as antineoplastics. For example, homoharringtonine (omacetaxine mepesuccinate or HHT), a treederived alkaloid from the conifer Cephalotaxus harringtonia, has shown promise in several clinical trials for myelodysplastic syndrome and in phase II clinical trials in patients with gleevec-resistant chronic myelogenous leukemia and in acute myeloid leukemia (AML) (Kantarjian et al 2001;Kim et al 2011). HHT is thought to inhibit peptide chain elongation by binding the A site of the ribosome, blocking aminoacyl-tRNA binding, and halting peptide chain elongation (Gurel et al 2009).…”

Section: Targeting Translation Initiation As An Antineoplastic Approachmentioning

confidence: 99%

Emerging Therapeutics Targeting mRNA Translation

Malina¹,

Mills²,

Pelletier³

2012

Cold Spring Harbor Perspectives in Biology

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A defining feature of many cancers is deregulated translational control. Typically, this occurs at the level of recruitment of the 40S ribosomes to the 5 0 -cap of cellular messenger RNAs (mRNAs), the rate-limiting step of protein synthesis, which is controlled by the heterotrimeric eukaryotic initiation complex eIF4F. Thus, eIF4F in particular, and translation initiation in general, represent an exploitable vulnerability and unique opportunity for therapeutic intervention in many transformed cells. In this article, we discuss the development, mode of action and biological activity of a number of small-molecule inhibitors that interrupt PI3K/mTOR signaling control of eIF4F assembly, as well as compounds that more directly block eIF4F activity.

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Omacetaxine mepesuccinate for the treatment of leukemia

Cited by 15 publications

References 68 publications

Current Management Approaches of Chronic Myeloid Leukemia

Current Management Approaches of Chronic Myeloid Leukemia

Omacetaxine mepesuccinate in the treatment of intractable chronic myeloid leukemia

Emerging Therapeutics Targeting mRNA Translation

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