(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

• ChemBase编号: 653
• 分子式: C29H32O13
• 平均质量: 588.55658
• 单一同位素质量: 588.18429108
• 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
• Canonical 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
• 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

名称和登记号

名称

• 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,^7.0^1^1,^1^5]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(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,^7.0^1^1,^1^5]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[7.7.0.0^{3,7}.0^{11,15}]hexadeca-1,3(7),8-trien-12-one
• IUPAC传统名: etoposide
• 商标名: Eposin; Etopophos; Lastet; Toposar; Vepesid; Vepesid J; Zuyeyidal
• 别名: (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)-one; EPEG; P 16-213; Vepesid J; Zuyeyidal; (-)-Etoposide; Etoposidum [INN-Latin]; trans-Etoposide; Etoposide; 4′-Demethylepipodophyllotoxin 9-(4,6-O-ethylidene-β-D-glucopyranoside); VP-16-213; Etoposide; EPA; Demethyl-epiodophyllotoxin ethylidene glucoside; Eposin; Vepesid; VP-16; Toposar

登记号

• CAS号: 33419-42-0
• EC号: 251-509-1
• MDL号: MFCD00869325
• PubChem SID: 160964116; 46505434; 24278178
• PubChem CID: 36462

理论计算性质

JChem

• Acid pKa: 9.329948
• 质子受体: 12
• 质子供体: 3
• LogD (pH = 5.5): 1.1603667
• LogD (pH = 7.4): 1.155394
• Log P: 1.1604304
• 摩尔折射率: 139.0212 cm^3
• 极化性: 55.93246 Å^3
• 极化表面积: 160.83 Å^2
• 可自由旋转的化学键: 5
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 0.73
• LOG S: -2.78
• 溶解度: 9.78e-01 g/l

分子性质

理化性质

• 溶解度: 58.7 mg/L; DMSO: soluble30 mg/mL; Methanol
• 外观: white powder; White Solid
• 熔点: 236-251 °C(lit.); 254-256°C
• 疏水性(logP): 1
• pKa: 9.8

安全信息

• 保存条件: -20°C; -20°C Freezer, Under Inert Atmosphere; Room Temperature (15-30°C)
• RTECS编号: KC0190000
• 欧盟危险性物质标志: 有毒(Toxic) (T); 有害性(Harmful) (Xn)
• 德国WGK号: 3
• 危险公开号: 45-22; R:22-45-36/37/38
• 安全公开号: 53-45; S:28-29-36/37/39-45-53
• GHS危险品标识: GHS07; GHS08
• GHS警示词: Danger
• GHS危险声明: H302-H350
• GHS警示性声明: P201-P308 + P313
• 个人保护装置: Eyeshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges

药理学性质

• 作用靶点: Topoisomerase
• 相关基因信息: human ... ABCB1(5243), CYP3A4(1576), TOP2A(7153)mouse ... Abcb1a(18671), Abcb1b(18669)rat ... Top2a(360243)

产品相关信息

• 纯度: ≥98%
• 成盐信息: Free Base
• 生物来源: synthetic

详细说明

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.

Toronto Research Chemicals - E933750

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

参考文献

• 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)