CAS 33419-42-0|Zuyeyidal|Vepesid|Toposar|Eposin|Etopophos|Etoposidum [INN-Latin]|etoposide|(10R,11R,15R,16S)-16-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-hexahydro-2H-pyrano[3,2-d][1,3]dioxin-6...

基本信息

化学结构

分子式

C₂₉H₃₂O₁₃

分子量

588.55658

精确质量

588.18429108

电荷

InChI

InChI=1S/C29H32O13/c1-11-36-9-20-27(40-11)24(31)25(32)29(41-20)42-26-14-7-17-16(38-10-39-17)6-13(14)21(22-15(26)8-37-28(22)33)12-4-18(34-2)23(30)19(5-12)35-3/h4-7,11,15,20-22,24-27,29-32H,8-10H2,1-3H3/t11-,15+,20-,21-,22+,24-,25-,26-,27-,29+/m1/s1

InChIKey

VJJPUSNTGOMMGY-MRVIYFEKSA-N

Canonic Smiles

COc1cc(cc(c1O)OC)[C@H]1[C@H]2C(=O)OC[C@@H]2[C@@H](c2c1cc1OCOc1c2)O[C@@H]1O[C@@H]2CO[C@H](O[C@H]2[C@@H]([C@H]1O)O)C

Isomeric Smiles

O([C@H]1[C@@H]2[C@@H]([C@@H](c3c1cc1OCOc1c3)c1cc(OC)c(O)c(OC)c1)C(=O)OC2)[C@@H]1O[C@H]2[C@@H](O[C@@H](OC2)C)[C@H](O)[C@H]1O

计算属性

JChem

LogD (pH = 7.4)

1.16

LogD (pH = 5.5)

1.16

Log P

1.16

可自由旋转的化学键

质子供体

质子受体

里宾斯基五规则

false

Acid pKa

9.33

极化表面积

160.83

极化性

58.83

摩尔折射率

139.02

LOG S

-3.40

数据来源

名称和标识

商标名

ZuyeyidalVepesidToposarEposinEtopophosVepesid JLastet

别名

Etoposidum [INN-Latin]trans-EtoposideEtoposide(-)-EtoposideVepesidEPADemethyl-epiodophyllotoxin ethylidene glucosideToposarVP-16EposinEtoposide4′-Demethylepipodophyllotoxin 9-(4,6-O-ethylidene-β-D-glucopyranoside)VP-16-213Vepesid JZuyeyidal(5R,5aR,8aR,9S)-9-[[4,6-O-(1R)-Ethylidene-β-D-glucopyranosyl]oxy]-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-oneEPEGP 16-213VP-164-demethylepipodophyllotoxin beta-D-ethylideneglucosideetoposide(-)-etoposide4'-Demethylepipodophyllotoxin 9-(4,6-O-(R)-ethylidene-beta-D-glucopyranoside)Etoposide9-((4,6-O-Ethylidine-beta-D-glucopyranosyl)oxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,4-dimethyloxyphenyl)furo(3',4'':6,7)naptho-(2,3-d)-1,3-dioxol-6(5aH)-onetrans-Etoposide

IUPAC传统名

etoposide (10R,11R,15R,16S)-16-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-hexahydro-2H-pyrano[3,2-d][1,3]dioxin-6-yl]oxy}-10-(4-hydroxy-3,5-dimethoxyphenyl)-4,6,13-trioxatetracyclo[7.7.0.0^{3,7}.0^{11,15}]hexadeca-1,3(7),8-trien-12-one

IUPAC标准名

(10R,11R,15R,16S)-16-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-hexahydro-2H-pyrano[3,2-d][1,3]dioxin-6-yl]oxy}-10-(4-hydroxy-3,5-dimethoxyphenyl)-4,6,13-trioxatetracyclo[7.7.0.0^{3,7}.0^{11,15}]hexadeca-1(9),2,7-trien-12-one (10R,11R,15R,16S)-16-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-hexahydro-2H-pyrano[3,2-d][1,3]dioxin-6-yl]oxy}-10-(4-hydroxy-3,5-dimethoxyphenyl)-4,6,13-trioxatetracyclo[7.7.0.0^{3,7}.0^{11,15}]hexadeca-1,3(7),8-trien-12-one (10R,11R,15R,16S)-16-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-hexahydro-2H-pyrano[3,2-d][1,3]dioxin-6-yl]oxy}-10-(4-hydroxy-3,5-dimethoxyphenyl)-4,6,13-trioxatetracyclo[7.7.0.0³,⁷.0¹¹,¹⁵]hexadeca-1,3(7),8-trien-12-one (10R,11R,15R,16S)-16-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-hexahydro-2H-pyrano[3,2-d][1,3]dioxin-6-yl]oxy}-10-(4-hydroxy-3,5-dimethoxyphenyl)-4,6,13-trioxatetracyclo[7.7.0.0³,⁷.0¹¹,¹⁵]hexadeca-1(9),2,7-trien-12-one (10R,11R,15R,16S)-16-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-hexahydro-2H-pyrano[3,2-d][1,3]dioxin-6-yl]oxy}-10-(4-hydroxy-3,5-dimethoxyphenyl)-4,6,13-trioxatetracyclo[7.7.0.0³,⁷.0¹¹,¹⁵]hexadeca-1,3(7),8-trien-12-one

国际非专利药品(INN)

Etoposidoetoposideetoposidum

名称和标识

数据登录号

EC号

251-509-1

CAS号

33419-42-0

PubChem SID

46505434242781781609641168145856

PubChem CID

36462

MDL号

MFCD00869325

数据登录号

化合物性质

安全信息

-20°C

Room Temperature (15-30°C)

-20°C Freezer, Under Inert Atmosphere

KC0190000

有害性 (Xn)

药理学性质

Topoisomerase

human ... ABCB1(5243), CYP3A4(1576), TOP2A(7153)mouse ... Abcb1a(18671), Abcb1b(18669)rat ... Top2a(360243)

化合物性质

分子相关蛋白质

分子图谱

暂无数据

点击上传数据

描述信息

DrugBank

DB00773

Drug Groups

approved

Description

A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [PubChem]

Indication

For use in combination with other chemotherapeutic agents in the treatment of refractory testicular tumors and as first line treatment in patients with small cell lung cancer. Also used to treat other malignancies such as lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme.

Pharmacology

Etoposide is an antineoplastic agent and an epipodophyllotoxin (a semisynthetic derivative of the podophyllotoxins). It inhibits DNA topoisomerase II, thereby ultimately inhibiting DNA synthesis. Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases. Two different dose-dependent responses are seen. At high concentrations (10 µg/mL or more), lysis of cells entering mitosis is observed. At low concentrations (0.3 to 10 µg/mL), cells are inhibited from entering prophase. It does not interfere with microtubular assembly. The predominant macromolecular effect of etoposide appears to be the induction of DNA strand breaks by an interaction with DNA-topoisomerase II or the formation of free radicals.

Toxicity

Side effects include alopecia, constipation, diarrhea, nausea and vomiting and secondary malignancies (leukemia).

Affected Organisms

Humans and other mammals

Biotransformation

Primarily hepatic (through O-demethylation via the CYP450 3A4 isoenzyme pathway) with 40% excreted unchanged in the urine.

Absorption

Absorbed well, time to peak plasma concentration is 1-1.5 hrs. Mean bioavailability is 50%.

Half Life

4-12 hours

Protein Binding

97%

Elimination

Etoposide is cleared by both renal and nonrenal processes, i.e., metabolism and biliary excretion. Glucuronide and/or sulfate conjugates of etoposide are also excreted in human urine. Biliary excretion of unchanged drug and/or metabolites is an important route of etoposide elimination as fecal recovery of radioactivity is 44% of the intravenous dose. Only 8% or less of an intravenous dose is excreted in the urine as radiolabeled metabolites of 14C-etoposide.

Clearance

* 33 - 48 mL/min [IV administration]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Selleck Chemicals

S1225

Research Area: Cancer
Biological Activity:
Two subclones of the OCI/AML-2 cell line, etoposide-sensitive (ES) and etoposide-resistant (ER) were used to investigate whether the Fas pathway is involved in etoposide-induced apoptosis in acute myeloblastic leukemia (AML). Both of the studied subclones expressed the Fas receptor (FasR), but only the ER cell line expressed the Fas ligand (FasL). Etoposide caused an increase in the mean fluorescence intensity of FasR in both subclones, and an induction of FasL in the ES subclone. However, no change in the numbers of apoptotic cells induced by etoposide was observed when FasR was blocked by an antagonist anti-Fas antibody, nor was an agonist anti-Fas antibody alone cytotoxic to the subclones or enhanced the cytotoxic effect of etoposide. [1]Etoposide phosphate is rapidly absorbed and converted to etoposide. Bioavailability averages 68% at doses up to 150 mg/m2/day. [3]

Sigma Aldrich

E1383

Biochem/physiol Actions
Etoposide is an antitumor agent that complexes with topoisomerase II and DNA to enhance double-strand and single-strand cleavage of DNA and reversibly inhibit religation. Blocks the cell cycle in in S-phase and G2-phase of the cell cycle; induces apoptosis in normal and tumor cell lines; inhibits synthesis of the oncoprotein Mdm2 and induces apoptosis in tumor lines that overexpress Mdm2.

TRC

E933750

A DNA topoisomerase II inhibitor. Semi-synthetic derivative of podophyllotoxin, related structurally to Teniposide. Antineoplastic.

描述信息

参考文献

PubChem文献

数据源提供

• Siitonen T et al. Leuk Res. 2000 Apr;24(4):281-8

• Burden, D.A., et al.: J. Biol. Chem., 271, 29238 (1996)

• Joel, S., et al.: Cancer Treat. Rev., 22, 179 (1996)

参考文献

生物活性