Paclitaxel (CHEM002979)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (6)XML
Record Information
Version1.0
Creation Date2014-08-29 04:49:18 UTC
Update Date2026-03-26 21:42:53 UTC
Accession NumberCHEM002979
Identification
Common NamePaclitaxel
ClassSmall Molecule
DescriptionA cyclodecane isolated from the bark of the Pacific yew tree, TAXUS brevifolia. It stabilizes microtubules in their polymerized form leading to cell death. 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. Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a US National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol. Later it was discovered that endophytic fungi in the bark synthesize paclitaxel.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Amine
  • Antineoplastic Agent, Phytogenic
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Plant Toxin
  • Tubulin Modulator
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
(2AR-(2aalpha,4beta,4abeta,6beta,9alpha(alpha r*,betas*),11alpha,12alpha,12balpha))-beta-(benzoylamino)-alpha-hydroxybenzenepropanoic acid 6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca(3,4)benz(1,2-b)oxet-9-yl esterChEBI
5beta,20-Epoxy-1,2-alpha,4,7beta,10beta,13alpha-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserineChEBI
TAXOLChEBI
Taxol aChEBI
(2AR-(2aalpha,4b,4abeta,6b,9a(a r*,betas*),11a,12a,12balpha))-b-(benzoylamino)-a-hydroxybenzenepropanoate 6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca(3,4)benz(1,2-b)oxet-9-yl esterGenerator
(2AR-(2aalpha,4b,4abeta,6b,9a(a r*,betas*),11a,12a,12balpha))-b-(benzoylamino)-a-hydroxybenzenepropanoic acid 6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca(3,4)benz(1,2-b)oxet-9-yl esterGenerator
(2AR-(2aalpha,4beta,4abeta,6beta,9alpha(alpha r*,betas*),11alpha,12alpha,12balpha))-beta-(benzoylamino)-alpha-hydroxybenzenepropanoate 6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca(3,4)benz(1,2-b)oxet-9-yl esterGenerator
(2AR-(2aalpha,4β,4abeta,6β,9α(α r*,betas*),11α,12α,12balpha))-β-(benzoylamino)-α-hydroxybenzenepropanoate 6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca(3,4)benz(1,2-b)oxet-9-yl esterGenerator
(2AR-(2aalpha,4β,4abeta,6β,9α(α r*,betas*),11α,12α,12balpha))-β-(benzoylamino)-α-hydroxybenzenepropanoic acid 6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca(3,4)benz(1,2-b)oxet-9-yl esterGenerator
5b,20-Epoxy-1,2-a,4,7b,10b,13a-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserineGenerator
5b,20-Epoxy-1,2-a,4,7b,10b,13a-hexahydroxytax-11-en-9-one 4,10-diacetic acid 2-benzoic acid 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserineGenerator
5beta,20-Epoxy-1,2-alpha,4,7beta,10beta,13alpha-hexahydroxytax-11-en-9-one 4,10-diacetic acid 2-benzoic acid 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserineGenerator
5Β,20-epoxy-1,2-α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserineGenerator
5Β,20-epoxy-1,2-α,4,7β,10β,13α-hexahydroxytax-11-en-9-one 4,10-diacetic acid 2-benzoic acid 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserineGenerator
7-Epi-paclitaxelHMDB
7-Epi-taxolHMDB
7-EpipaclitaxelHMDB
7-EpitaxolHMDB
ABI-007HMDB
7 Epi taxolHMDB
OnxolHMDB
Paclitaxel, (4 alpha)-isomerHMDB
PaxeneHMDB
Taxol, brisHMDB
AnzataxHMDB
Bris taxolHMDB
PraxelHMDB
Chemical FormulaC47H51NO14
Average Molecular Mass853.906 g/mol
Monoisotopic Mass853.331 g/mol
CAS Registry Number33069-62-4
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[11.3.1.0³,¹⁰.0⁴,⁷]heptadec-13-en-2-yl benzoate
Traditional Namepaclitaxel
SMILES[H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)C4=CC=CC=C4)C4=CC=CC=C4)C(C)=C([C@@H](OC(C)=O)C(=O)[C@]1(C)[C@@H](O)C[C@H]1OC[C@@]21OC(C)=O)C3(C)C
InChI IdentifierInChI=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
InChI KeyRCINICONZNJXQF-MZXODVADSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as diphenylmethanes. Diphenylmethanes are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Aralkylamine
  • Amino acid or derivatives
  • Carboxylic acid ester
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid derivative
  • Monocarboxylic acid or derivatives
  • Amine
  • Organooxygen compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Carbonyl group
  • Organic nitrogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Paclitaxel PathwayNot AvailableNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point216-217°C
Boiling PointNot Available
SolubilityInsoluble
Predicted Properties
PropertyValueSource
Water Solubility0.0056 g/LALOGPS
logP3.2ALOGPS
logP3.54ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)10.36ChemAxon
pKa (Strongest Basic)-1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area221.29 ŲChemAxon
Rotatable Bond Count14ChemAxon
Refractivity218.29 m³·mol⁻¹ChemAxon
Polarizability87.17 ųChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-3971000000-2a76bfe38de6d5790a39Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-029i-0030050690-c48555dd5b3f5acd814bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0900-0780090340-954315fc743a0eaf982fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a6r-1510290000-5903f2c1cdc9b5323c84Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0hgc-2240060490-3ffb6f7c9cb421bdaf33Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-069c-3120090220-f3e24aad4024a1fc8393Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-7621090000-c809e0c049a10dcb9b96Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00kr-0490030120-fdc08616b5cb9529e3d2Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-1891031120-01a12386c92de396878aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0560-8936200010-0ac0a443ec5729fc53a0Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0fai-6590020450-c72eb5c12b53622b041aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-06vi-6290050020-bb22e99420188babae6eSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9400000010-9b1381f8b9e6160e204bSpectrum
Toxicity Profile
Route of ExposureWhen a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the maximum plasma concentration (Cmax) is 195 ng/mL, while the AUC is 6300 ng*h/mL.
Mechanism of ToxicityPaclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the β subunit of tubulin. Tubulin is the 'building block' of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.
MetabolismHepatic. 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. Route of 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. Half Life: When a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the elimination half=life is 52.7 hours.
Toxicity ValuesRat (ipr) LD50=32530 µg/kg.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed in the treatment of Kaposi's sarcoma and cancer of the lung, ovarian, and breast. Abraxane™ is specfically indicated for the treatment of metastatic breast cancer and locally advanced or metastatic non-small cell lung cancer.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Concentrations
Not Available
DrugBank IDDB01229
HMDB IDHMDB0015360
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDC00002365
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkPaclitaxel
Chemspider ID10368587
ChEBI ID45863
PubChem Compound ID36314
Kegg Compound IDC07394
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Hendricus B. A. de Bont, Ruben G. G. Leenders, Johan W. Scheeren, Hidde J. Haisma, Dick de Vos, “Paclitaxel prodrugs, method for preparation as well as their use in selective chemotherapy.” U.S. Patent US5760072, issued September, 1989.

MSDSLink
General References
1. 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.
2. 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.
3. 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.
4. 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.
5. Authors unspecified: ABI 007. Drugs R D. 2004;5(3):155-9.
6. Gaitanis A, Staal S: Liposomal doxorubicin and nab-paclitaxel: nanoparticle cancer chemotherapy in current clinical use. Methods Mol Biol. 2010;624:385-92. doi: 10.1007/978-1-60761-609-2_26.
7. Simons K, Toomre D: Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9.
8. Watson AD: Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global approach to lipid analysis in biological systems. J Lipid Res. 2006 Oct;47(10):2101-11. Epub 2006 Aug 10.
9. Sethi JK, Vidal-Puig AJ: Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res. 2007 Jun;48(6):1253-62. Epub 2007 Mar 20.
10. Lingwood D, Simons K: Lipid rafts as a membrane-organizing principle. Science. 2010 Jan 1;327(5961):46-50. doi: 10.1126/science.1174621.
11. The lipid handbook with CD-ROM