HCID285033

Omacetaxine Mepesuccinate

1-O-[(2S,3S,6R)-4-methoxy-16,18-dioxa-10-azapentacyclo[11.7.0.02,6.06,10.015,19]icosa-1(20),4,13,15(19)-tetraen-3-yl] 4-O-methyl (2R)-2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate

C29H39NO9545.6 g/molCAS 26833-87-4

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IDENTITY

结构与身份

标准SMILES: COC(=O)C[C@](O)(CCCC(C)(C)O)C(=O)O[C@@H]1C(OC)=C[C@]23CCCN2CCc2cc4c(cc2[C@H]13)OCO4
InChIKey: HYFHYPWGAURHIV-JFIAXGOJSA-N
分子式: C29H39NO9
平均分子量: 545.6 g/mol
单同位素质量: 545.26248182

COMPUTED

结构计算性质

已同步

XLogP: 0.8
极性表面积: 124 Å²
氢键供体: 2
氢键受体: 10
可旋转键: 11
重原子: 39
形式电荷: 0
复杂度: 968

PROPERTIES

实验与物化性质

来源：PubChem

Stability/Shelf Life

Bulk: Room temperature and 60°C stability studies indicate the chemical to be stable for at least 30 days (HPLC). Solution: Room temperature stability studies for homoharringtonine (1mg/mL) in 10% ethanol showed 16% decomposition after 24 hours and 35% decomposition after 96 hours (HPLC).

HAZARDS

危害信息

来源：PubChem

Regulatory Information

Cephalotaxine, 4-methyl (2R)-2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate (ester): Does not have an individual approval but may be used under an appropriate group standard

TOXICITY

毒理信息

来源：PubChem

Drug Induced Liver Injury

Drug Induced Liver Injury Rank (DILIrank 2.0)

Omacetaxine mepesuccinate

Ambiguous-DILI-concern

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

Toxicity Data

Mouse(ip): LD50: 1960 ug/kg

Mouse(ip): LD50: 6.5 mg/kg

REGULATORY

法规信息

来源：PubChem

Regulatory Information

Cephalotaxine, 4-methyl (2R)-2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate (ester): Does not have an individual approval but may be used under an appropriate group standard

PHARMACOLOGY

药理信息

来源：PubChem

ATC Code

L - Antineoplastic and immunomodulating agents；L01 - Antineoplastic agents；L01X - Other antineoplastic agents；L01XX - Other antineoplastic agents；L01XX40 - Omacetaxine mepesuccinate

QL - Antineoplastic and immunomodulating agents；QL01 - Antineoplastic agents；QL01X - Other antineoplastic agents；QL01XX - Other antineoplastic agents；QL01XX40 - Omacetaxine mepesuccinate

Protein Binding

Plasma protein binding is equal or less than 50%.

Pharmacodynamics

The pharmacodynamics of homoharringtonine is not fully understood. It is known that homoharringtonine is involved with protein synthesis inhibition and this leads to its antineoplastic activity.

Mechanism of Action

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.

Biological Half-Life

Homoharringtonine has a half life of about 6 hours after subcutaneous administration.

Metabolism/Metabolites

Homoharringtonine has undergoes little hepatic metabolism and is mostly metabolized to 4’-DMHHT by plasma esterase hydrolysis.

MeSH Pharmacological Classification

Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.

Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.

Absorption, Distribution and Excretion

Homoharringtonine absorption was not quantified, but maximum concentration is reached after about 30 mins.

The main route of elimination for homoharringtonine is still unknown, but renal elimination is less than 15%.

Homoharringtonine has a steady state Vd of 141 ± 93.4 L.

Clearance for homoharringtonine was not quantified.

ALIASES

名称与别名

共 107 条

Omacetaxine mepesuccinateCeflatoninMyelostatSynriboCGX-635OmaproHomoharringtonin(-)-homoharringtonineNSC-141633mepesuccinate d'omacetaxinemepesuccinato de omacetaxinaCHEBI:71019(2'R,3S,4S,5R)-(-)-homoharringtonineomacetaxini mepesuccinas6FG8041S5B1-O-[(2S,3S,6R)-4-methoxy-16,18-dioxa-10-azapentacyclo[11.7.0.02,6.06,10.015,19]icosa-1(20),4,13,15(19)-tetraen-3-yl] 4-O-methyl (2R)-2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioateCephalotaxine 4-Methyl (2R)-2-Hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate (Ester)Cephalotaxine, 4-methyl (2R)-2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate (ester)DTXCID80256781-((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

REACTIONS