Omacetaxine mepesuccinate kháng L1210

Two homoharringtonine resistant leukemic cell lines(K562 HHT and ...

Homoharringtonine  (Omacetaxine mepesuccinate) kháng L1210

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Omacetaxine mepesuccinate

Clinical data
Trade names	Synribo
AHFS/Drugs.com	Monograph
License data	US FDA: Omacetaxine_mepesuccinate
Pregnancy category	US: D (Evidence of risk)
Routes of administration	Subcutaneous, intravenous infusion
ATC code	L01XX40 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Protein binding	50%
Metabolism	Mostly via plasma esterases
Biological half-life	6 hours
Excretion	Urine (≤15% unchanged)
Identifiers
IUPAC name[show]
CAS Number	26833-87-4
PubChem CID	285033
IUPHAR/BPS	7454
ChemSpider	251215
UNII	6FG8041S5B
KEGG	D08956
ChEBI	CHEBI:71019
ECHA InfoCard	100.164.439
Chemical and physical data
Formula	C29H39NO9
Molar mass	545.62 g/mol
3D model (Jmol)	Interactive image
SMILES[show]
InChI[show]

Omacetaxine mepesuccinate (INN, trade names Synribo or Myelostat ), formerly named as homoharringtonine or HHT, is a pharmaceutical drug substance that is indicated for treatment of chronic myeloid leukemia (CML). It is a natural product first discovered in Cephalotaxus harringtonii, now manufactured by hemi-synthesis. 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).^[1]

Contents

  [hide] 

• 1Medical uses
• 2Adverse effects
• 3Mechanism of action
• 4References

Medical uses[edit]

Omacetaxine/homoharringtonine is indicated for use as a treatment for patients with chronic myeloid leukaemia who are resistant or intolerant of tyrosine kinase inhibitors.^[2][3][4]

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.^[5] A study in patients who had failed imatinib and who had the drug resistant T315I mutation achieved cytogenetic response in 28% of patients and hematologic response in 80% of patients, according to preliminary data.^[6]

Phase I studies including a small number of patients have shown benefit in treating myelodysplastic syndrome(MDS, 25 patients)^[7] and acute myelogenous leukaemia (AML, 76 patients).^[8] Patients with solid tumors did not benefit from omacetaxine.^[9]

Adverse effects[edit]

By frequency:^[1][2]
Very common (>10% frequency):

• Diarrhoea
• Myelosuppression^†
• Injection site reactions
• Nausea
• Fatigue
• Fever
• Muscle weakness
• Joint pain
• Headache
• Cough
• Hair loss
• Constipation
• Nosebleeds
• Upper abdominal pain
• Pain in the extremities
• Oedema
• Vomiting
• Back pain
• Hyperglycemia, sometimes extreme
• Gout
• Rash
• Insomnia

Common (1-10% frequency):

• Seizures
• Haemorrhage

^† Myelosuppression, including: thrombocytopenia, anaemia, neutropenia and lymphopenia, in descending order of frequency.

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.^[10]