| 药品名称 |
Omacetaxine mepesuccinate
|
| 分子靶点 |
50S ribosomal protein L2;60S ribosomal protein L3
|
| 药物类型 |
Small Molecule
|
| 研发阶段 |
Approved, Investigational
|
| 药物描述 |
Omacetaxine mepesuccinate (formerly known as HHT or Homoharringtonine), is a cephalotaxine ester and protein synthesis inhibitor with established clinical activity as a single agent in hematological malignancies. Omacetaxine mepesuccinate is synthesized from cephalotaxine, which is an extract from the leaves of the plant, Cephalotaxus species. In October 2005, omacetaxine mepesuccinate received Orphan Drug designation from the EMEA for the treatment of chronic myeloid leukemia (CML). Then in March 2006, it received Orphan Drug status from the FDA for the treatment of CML. In November 2006, omacetaxine mepesuccinate, for the treatment of CML, was granted Fast Track designation by the FDA. Most recently, in October 2012, omacetaxine mepesuccinate was marketed under the brand name Synribo and FDA approved for patients who are intolerant and/or resistant to two or more tyrosine kinase inhibitors used to treat accelerated or chronic phase CML.
|
| 结构式 |
 |
| 药物别名 |
(−)-homoharringtonine;(2'R,3S,4S,5R)-(−)-homoharringtonine;HHT;Homoharringtonin;Homoharringtonine;mepesuccinato de omacetaxina;Omacetaxine mepesuccinate
|
| 治疗类别 |
Alkaloids;Angiogenesis Modulating Agents;Antineoplastic Agents;Antineoplastic Agents, Phytogenic;Antineoplastic and Immunomodulating Agents;Apoptosis;Benzazepines;Growth Inhibitors;Growth Substances;Leukemia, Myelogenous, Chronic, BCR-ABL Positive
|
| UNII号 |
6FG8041S5B
|
| CAS号 |
26833-87-4
|
| 分子量 |
545.6213
|
| 分子式 |
C29H39NO9
|
| 适应症 |
Used in patients who are intolerant and/or resistant to two or more tyrosine kinase inhibitors used to treat accelerated or chronic phase CML.
|
| 药效学 |
The pharmacodynamics of homoharringtonine is not fully understood. It is known that homoharringtonine is involvedwith protein synthesis inhibition and this leads to its antineoplastic activity.
|
| 作用机制 |
Homoharringtonine inhibits protein synthesis by not directly binding to Bcr-Abl. It binds to the A-site cleft in the large ribosomal subunit, which affects chain elongation and prevents protein synthesis.
|
| 吸收 |
Homoharringtonine absorption was not quantified, but maximum concentration is reached after about 30 mins.
|
| 分布量 |
Homoharringtonine has a steady state Vd of 141 ± 93.4 L.
|
| 蛋白结合 |
Plasma protein binding is equal or less than 50%.
|
| 代谢 |
Homoharringtonine has undergoes little hepatic metabolism and is mostly metabolized to 4’-DMHHT by plasma esterase hydrolysis.
|
| 排泄 |
The main route of elimination for homoharringtonine is still unknown, but renal elimination is less than 15%.
|
| 半衰期 |
Homoharringtonine has a half life of about 6 hours after subcutaneous administration.
|
| 清除 |
Clearance for homoharringtonine was not quantified.
|
| 毒理 |
The most severe adverse effects after homoharringtonine administration are myelosuppression, bleeding, hyperglycemia, and fetal harm.
|
| ATC代码 |
L01XX40
|
