| 药品名称 |
Romidepsin
|
| 分子靶点 |
Tumor necrosis factor ligand superfamily member 12
|
| 酶 |
Cytochrome P450 3A4;Cytochrome P450 3A5;Cytochrome P450 1A1;Cytochrome P450 2B6;Cytochrome P450 2C19
|
| 药物类型 |
Small Molecule
|
| 研发阶段 |
Approved, Investigational
|
| 药物描述 |
Romidepsin is a selective inhibitor of histone deacetylase, approved in the US in 2009 for the treatment of cutaneous T-cell lymphoma (CTCL) or/and peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior systemic therapy. These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.
|
| 结构式 |
 |
| 药物别名 |
Romidepsin;Romidepsina;Romidepsine;Romidepsinum
|
| 治疗类别 |
Amino Acids, Peptides, and Proteins;Antibiotics, Antineoplastic;Antineoplastic Agents;Antineoplastic and Immunomodulating Agents;Cytochrome P-450 CYP2B6 Substrates;Cytochrome P-450 CYP3A Substrates;Cytochrome P-450 CYP3A4 Substrates;Cytochrome P-450 CYP3A5 Substrates;Highest Risk QTc-Prolonging Agents;Histone Deacetylase Inhibitors;OATP1B3 substrates;P-glycoprotein/ABCB1 Substrates;Peptides;Peptides, Cyclic;QTc Prolonging Agents
|
| UNII号 |
CX3T89XQBK
|
| CAS号 |
128517-07-7
|
| 分子量 |
540.69
|
| 分子式 |
C24H36N4O6S2
|
| 适应症 |
For the treatment of cutaneous T-cell lymphoma (CTCL) or/and peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior systemic therapy. These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.
|
| 作用机制 |
Romidepsin is a prodrug, where it becomes active once taken up into the cell. The active metabolite has a free thiol group, which interacts with zinc ions in the active site of class 1 and 2 HDAC enzymes, resulting in inhibition of its enzymatic activity. Certain tumors have over expressed HDACs and downregulated/mutated histone acetyltransferases. This imbalance of HDAC relative to histone acetyltransferase can lead to a decrease in regulatory genes, ensuing tumorigenesis. Inhibition of HDAC may restore normal gene expression in cancer cells and result in cell cycle arrest and apoptosis.
|
| 吸收 |
Romidepsin exhibited linear pharmacokinetics at standard doses.
|
| 分布量 |
44.5L
|
| 蛋白结合 |
Highly protein bound in plasma (92%-94%)
|
| 代谢 |
Romidepsin undergoes extensive hepatic metabolism in vitro primarily by CYP3A4 with minor contribution from CYP3A5, CYP1A1, CYP2B6 and CYP2C19.
|
| 半衰期 |
Approximately 3 hours
|
| 清除 |
8.4L/h
|
| 毒理 |
Risk factor D in pregnancy. It is not known if romidepsin is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.The majority of patients receiving romidepsin experience nausea, vomiting, and anorexia.
|
| ATC代码 |
L01XX39
|
