(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 ID: 1098
• Molecular Formular: C47H51NO14
• Molecular Mass: 853.90614
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: (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 Traditional name: 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
• Brand Name: Epitaxol; LipoPac; Onxol; Paxceed; Paxene; Taxol; Taxol A; Xorane; Vascular Wrap; Abraxane
• Synonyms: 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

Database IDs

• CAS Number: 33069-62-4
• MDL Number: MFCD00869953
• PubChem SID: 160964561; 46506910
• PubChem CID: 36314
• CHEBI ID: 45863
• ATC CODE: L01CD03; L01CD01
• CHEMBL: 48
• Chemspider ID: 10368587
• DrugBank ID: DB01229
• IUPHAR ligand ID: 2770
• KEGG ID: D00491
• Unique Ingredient Identifier: P88XT4IS4D
• Wikipedia Title: Paclitaxel

CALCULATED PROPERTIES

JChem

• Acid pKa: 10.364198
• H Acceptors: 10
• H Donor: 4
• LogD (pH = 5.5): 3.538834
• LogD (pH = 7.4): 3.538369
• Log P: 3.53884
• Molar Refractivity: 218.2945 cm^3
• Polarizability: 86.54275 Å^3
• Polar Surface Area: 221.29 Å^2
• Rotatable Bonds: 14
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 3.2
• LOG S: -5.19
• Solubility (Water): 5.56e-03 g/l

PROPERTIES

Physical Property

• Solubility: Insoluble; Methanol
• Apperance: Powder; White Solid
• Melting Point: 213-223°C; 214-216°C
• Vapor Pressure: < 1.12 x 10-7 Torr
• Hydrophobicity(logP): 3

Safety Information

• Storage Condition: -20°C Freezer; Room Temperature (15-30°C)
• RTECS: DA8340700
• European Hazard Symbols: Toxic (T)
• UN Number: 2811
• Hazard Class: 6.1
• Packing Group: III
• Australian Hazchem: 2X
• Risk Statements: R:25
• Safety Statements: S:28-36/37/39-45-53
• EU Classification: T2
• EU Hazard Identification Number: 6.1B
• Emergency Response Guidebook(ERG) Number: 154

Pharmacology Properties

• Admin Routes: iv
• Bioavailability: 6.5% (oral)
• Excretion: Fecal and urinary
• Half Life: 5.8 hours
• Metabolism: Hepatic (CYP2C8 and CYP3A4)
• Protein Bound: 89 to 98%
• Legal Status: Rx-only (US)
• Pregnancy Category: D (US)
• Mechanism of Action: Binds to the beta subunit of tubulin; Interferes with the normal function of microtubule growth by hyper-stabilisation of their structure

Product Information

• Purity: >98%; 95+%
• Biological Source: Isol. from the stem bark of Taxus brevifolia and Taxus cuspidata (Taxaceae)
• Application(s): 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

DETAILS

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

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