(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1,9-dihydroxy-15-{[(2R,3S)-2-hydroxy-3-phenyl-3-(phenylformamido)propanoyl]oxy}-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl benzoate

• ChemBase编号: 1098
• 分子式: C47H51NO14
• 平均质量: 853.90614
• 单一同位素质量: 853.33095532
• SMILES: [C@H]1(OC(=O)c2ccccc2)[C@@H]2[C@@]3(CO[C@@H]3C[C@@H]([C@]2(C(=O)[C@@H](C2=C([C@H](C[C@]1(O)C2(C)C)OC(=O)[C@@H]([C@H](c1ccccc1)NC(=O)c1ccccc1)O)C)OC(=O)C)C)O)OC(=O)C
• Canonical SMILES: CC(=O)O[C@H]1C(=O)[C@]2(C)[C@@H](O)C[C@@H]3[C@]([C@H]2[C@@H]([C@]2(C(C1=C(C)[C@@H](OC(=O)[C@@H]([C@H](c1ccccc1)NC(=O)c1ccccc1)O)C2)(C)C)O)OC(=O)c1ccccc1)(CO3)OC(=O)C
• InChI: InChI=1S/C47H51NO14/c1-25-31(60-43(56)36(52)35(28-16-10-7-11-17-28)48-41(54)29-18-12-8-13-19-29)23-47(57)40(61-42(55)30-20-14-9-15-21-30)38-45(6,32(51)22-33-46(38,24-58-33)62-27(3)50)39(53)37(59-26(2)49)34(25)44(47,4)5/h7-21,31-33,35-38,40,51-52,57H,22-24H2,1-6H3,(H,48,54)/t31-,32-,33+,35-,36+,37+,38-,40-,45+,46-,47+/m0/s1
• InChIKey: RCINICONZNJXQF-MZXODVADSA-N

名称和登记号

名称

• IUPAC标准名: (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1,9-dihydroxy-15-{[(2R,3S)-2-hydroxy-3-phenyl-3-(phenylformamido)propanoyl]oxy}-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl benzoate; (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1,9-dihydroxy-15-{[(2R,3S)-2-hydroxy-3-phenyl-3-(phenylformamido)propanoyl]oxy}-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^3,^1^0.0^4,^7]heptadec-13-en-2-yl benzoate
• IUPAC传统名: TAX; paclitaxel; taxol; (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1,9-dihydroxy-15-{[(2R,3S)-2-hydroxy-3-phenyl-3-(phenylformamido)propanoyl]oxy}-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^3,^1^0.0^4,^7]heptadec-13-en-2-yl benzoate
• 商标名: Epitaxol; LipoPac; Onxol; Paxceed; Paxene; Taxol; Taxol A; Xorane; Vascular Wrap; Abraxane
• 别名: 7-epi-Paclitaxel; 7-epi-Taxol; 7-Epipaclitaxel; 7-Epitaxol; ABI-007; Paclitaxel; Taxol®; Taxol A; Anzatax; Paclitaxel; Abraxane; Genaxol; Genetaxyl; OncoGel; Onxal; Pacliex; (-)-Paclitaxel; Taxol; Yewtaxan; NSC 125973

登记号

• CAS号: 33069-62-4
• MDL号: MFCD00869953
• PubChem SID: 160964561; 46506910
• PubChem CID: 36314
• CHEBI ID: 45863
• ATC码: L01CD03; L01CD01
• CHEMBL: 48
• Chemspider ID: 10368587
• DrugBank ID: DB01229
• IUPHAR配体索引: 2770
• KEGG ID: D00491
• 美国药典/FDA物质标识码: P88XT4IS4D
• 维基百科标题: Paclitaxel

理论计算性质

JChem

• Acid pKa: 10.364198
• 质子受体: 10
• 质子供体: 4
• LogD (pH = 5.5): 3.538834
• LogD (pH = 7.4): 3.538369
• Log P: 3.53884
• 摩尔折射率: 218.2945 cm^3
• 极化性: 86.54275 Å^3
• 极化表面积: 221.29 Å^2
• 可自由旋转的化学键: 14
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 3.2
• LOG S: -5.19
• 溶解度: 5.56e-03 g/l

分子性质

理化性质

• 溶解度: Insoluble; Methanol
• 外观: Powder; White Solid
• 熔点: 213-223°C; 214-216°C
• 蒸汽压: < 1.12 x 10-7 Torr
• 疏水性(logP): 3

安全信息

• 保存条件: -20°C Freezer; Room Temperature (15-30°C)
• RTECS编号: DA8340700
• 欧盟危险性物质标志: 有毒(Toxic) (T)
• 联合国危险货物编号: 2811
• 联合国危险货物等级: 6.1
• 联合国危险货物包装类别(PG): III
• 澳大利亚Hazchem: 2X
• 危险公开号: R:25
• 安全公开号: S:28-36/37/39-45-53
• 欧盟危险货物分类: T2
• 欧盟危险识别号(EUHIN): 6.1B
• 美国ERG指导号: 154

药理学性质

• 给药途径: iv
• 生物利用度: 6.5% (oral)
• 排泄: Fecal and urinary
• 半衰期: 5.8 hours
• 代谢: Hepatic (CYP2C8 and CYP3A4)
• 蛋白结合率: 89 to 98%
• 法定药品分级: Rx-only (US)
• 妊娠期药物分类: D (US)
• 生物活性机理: Binds to the beta subunit of tubulin; Interferes with the normal function of microtubule growth by hyper-stabilisation of their structure

产品相关信息

• 纯度: >98%; 95+%
• 生物来源: Isol. from the stem bark of Taxus brevifolia and Taxus cuspidata (Taxaceae)
• 应用领域: Also shown to be active against oomycete fungi; Antileukaemic and antineoplastic agent, esp. against melanoma and ovarian tumours; Biochemical tool extensively used to study cellular shape and function.; Use limited by low solubility and scarce availability of Taxus brevifolia bark

详细说明

MP Biomedicals - 02193532

(Taxol?) From the Pacific Yew Tree Taxus brevifolia Antitumor agent which lowers the critical concentration for tubulin polymerization and reversibly binds to tubulin prohibiting depolymerization. Purity: >98%

DrugBank - DB01229

• Drug Groups: approved
• Description: A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS brevifolia. It stabilizes microtubules in their polymerized form leading to cell death. [PubChem] ABI-007 (Abraxane) is the latest attempt to improve upon paclitaxel, one of the leading chemotherapy treatments. Both drugs contain the same active agent, but Abraxane is delivered by a nanoparticle technology that binds to albumin, a natural protein, rather than the toxic solvent known as Cremophor. It is thought that delivering paclitaxel with this technology will cause fewer hypersensitivity reactions and possibly lead to greater drug uptake in tumors.
• Indication: Used in the treatment of Kaposi's sarcoma and cancer of the lung, ovarian, and breast.
• Pharmacology: Paclitaxel is a taxoid antineoplastic agent indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast cancer. Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.
• Toxicity: Rat (ipr) LD₅₀=32530 µg/kg. Symptoms of overdose include bone marrow suppression, peripheral neurotoxicity, and mucositis. Overdoses in pediatric patients may be associated with acute ethanol toxicity.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6a-hydrox-ypaclitaxel by the cytochrome P450 isozyme CYP2C8; and to two minor metabolites, 3’-p-hydroxypaclitaxel and 6a, 3’-p-dihydroxypaclitaxel, by CYP3A4.
• Absorption: I.V injected
• Half Life: Average distribution half-life of 0.34 hours and an average elimination half-life of 5.8 hours.
• Protein Binding: 89%-98%
• Elimination: In 5 patients administered a 225 or 250 mg/m2 dose of radiolabeled paclitaxel as a 3-hour infusion, a mean of 71% of the radioactivity was excreted in the feces in 120 hours, and 14% was recovered in the urine.
• Distribution: * 227 to 688 L/m2
• Clearance: * 21.7 L/h/m2 [Dose 135 mg/m2, infusion duration 24 h]; * 23.8 L/h/m2 [Dose 175 mg/m2, infusion duration 24 h]; * 7 L/h/m2 [Dose 135 mg/m2, infusion duration 3 h]; * 12.2 L/h/m2 [Dose 175 mg/m2, infusion duration 3 h]
• References: Wall ME, Wani MC: Camptothecin and taxol: discovery to clinic--thirteenth Bruce F. Cain Memorial Award Lecture. Cancer Res. 1995 Feb 15;55(4):753-60. [Pubmed] ; Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT: Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc. 1971 May 5;93(9):2325-7. [Pubmed] ; Fuchs DA, Johnson RK: Cytologic evidence that taxol, an antineoplastic agent from Taxus brevifolia, acts as a mitotic spindle poison. Cancer Treat Rep. 1978 Aug;62(8):1219-22. [Pubmed] ; Saville MW, Lietzau J, Pluda JM, Feuerstein I, Odom J, Wilson WH, Humphrey RW, Feigal E, Steinberg SM, Broder S, et al.: Treatment of HIV-associated Kaposi's sarcoma with paclitaxel. Lancet. 1995 Jul 1;346(8966):26-8. [Pubmed] ; ABI 007. Drugs R D. 2004;5(3):155-9. [Pubmed] ; Gaitanis A, Staal S: Liposomal doxorubicin and nab-paclitaxel: nanoparticle cancer chemotherapy in current clinical use. Methods Mol Biol. 2010;624:385-92. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Toronto Research Chemicals - P132500

An antineoplastic. Used in the study of structure and function of microtubles into tubulin. Paclitaxel is now used to treat patients with lung, ovarian, breast cancer, head and neck cancer, and advanced forms of Kaposi's sarcoma. Paclitaxel is a mitotic i

参考文献

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• Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT: Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc. 1971 May 5;93(9):2325-7. Pubmed
• Fuchs DA, Johnson RK: Cytologic evidence that taxol, an antineoplastic agent from Taxus brevifolia, acts as a mitotic spindle poison. Cancer Treat Rep. 1978 Aug;62(8):1219-22. Pubmed
• Saville MW, Lietzau J, Pluda JM, Feuerstein I, Odom J, Wilson WH, Humphrey RW, Feigal E, Steinberg SM, Broder S, et al.: Treatment of HIV-associated Kaposi's sarcoma with paclitaxel. Lancet. 1995 Jul 1;346(8966):26-8. Pubmed
• Gaitanis A, Staal S: Liposomal doxorubicin and nab-paclitaxel: nanoparticle cancer chemotherapy in current clinical use. Methods Mol Biol. 2010;624:385-92. Pubmed
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