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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2020-02-26 21:41:30 UTC
HMDB IDHMDB0015378
Secondary Accession Numbers
  • HMDB0042023
  • HMDB15378
  • HMDB42023
Metabolite Identification
Common NameDocetaxel
DescriptionDocetaxel (sold under the brand name Taxotere) is a clinically well-established anti-mitotic chemotherapy medication (that is, it interferes with cell division). It is used mainly for the treatment of breast, ovarian, prostate, and non-small cell lung cancer. Docetaxel binds to microtubules reversibly with high affinity and has a maximum stoichiometry of 1 mole docetaxel per mole tubulin in microtubules. Docetaxel has been FDA-approved to treat patients who have locally advanced, or metastatic breast, or non-small-cell lung cancer who have undergone anthracycline-based chemotherapy and failed to stop cancer progression or relapsed. Docetaxel has a European approval for use in hormone-refractory prostate cancer. Docetaxel is a chemotherapeutic agent and is a cytotoxic compound. It is effectively a biologically damaging drug. As with all chemotherapy, adverse effects are common and many varying side-effects have been documented. Because docetaxel is a cell-cycle specific agent, it is cytotoxic to all dividing cells in the body. This includes tumour cells as well as hair follicles, bone marrow, and other germ cells. For this reason, common chemotherapy side effects such as alopecia occur (this can sometimes be permanent). The drug company Sanofi Aventis claims that they do not routinely keep this data. A survey being conducted in northwest France aims to establish exactly how many patients are being disfigured in this way. Independent studies show it could be as high as 6.3% which puts this ASE in the 'common and frequent' classification. Docetaxel is mainly metabolized in the liver by the cytochrome P450 CYP3A4 and CYP3A5 subfamilies of isoenzymes. Metabolism is principally oxidative and at the tert-butylpropionate side chain, resulting first in an alcohol docetaxel (M2), which is then cyclized to three further metabolites (M1, M3, and M4). M1 and M3 are two diastereomeric hydroxyoxazolidinones and M4 is an oxazolidinedione. Phase II trials of 577 patients showed that docetaxel clearance is related to body surface area and plasma levels of hepatic enzyme alpha-1-acid glycoprotein. Docetaxel is of the chemotherapy drug class taxane and is a semi-synthetic analogue of paclitaxel (Taxol), an extract from the bark of the rare Pacific yew tree Taxus brevifolia. Due to the scarcity of paclitaxel, extensive research was carried out which lead to the formulation of docetaxel, an esterified product of 10-deacetylbaccatin III. It was extracted from the renewable and readily available European yew tree. Drug interactions may be the result of altered pharmacokinetics or pharmacodynamics due to one of the drugs involved. Cisplatin, dexamethasone, doxorubicin, etoposide, and vinblastine are all potentially co-administered with docetaxel and did not modify docetaxel plasma binding in phase II studies. Cisplatin is known to have a complex interaction with some CYPs and has, in some events, been shown to reduce docetaxel clearance by up to 25%. Anticonvulsants induce some metabolic pathways relevant to docetaxel. CYP450 and CYP3A show increased expression in response to the use of anticonvulsants and the metabolism of docetaxel metabolite M4 is processed by these CYPs. A corresponding increase in clearance of M4 by 25% is observed in patients taking phenytoin and phenobarbital, common anticonvulsants. STAMPEDE is a UK-based six-arm, five-stage, open-label randomized controlled trial involving more than 3000 men. Arms C and E of this trial involve administering docetaxel to men starting long-term hormone therapy for the first time. This could be newly diagnosed metastatic, non-metastatic, or high-risk, previously-treated prostate cancer. The trial tests the value of the drug earlier in the treatment pathway instead of waiting until it has become androgen-independent.
Structure
Data?1582753290
Synonyms
ValueSource
N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetylpaclitaxelChEBI
N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxolChEBI
TXLChEBI
TaxotereKegg
Docetaxel anhydrousHMDB
Docetaxel, trihydrateHMDB
Docetaxel trihydrateHMDB
DocetaxolHMDB
N-Debenzoyl-N-tert-butoxycarbonyl-10-deacetyltaxolHMDB
Taxoltere metroHMDB
Docetaxel hydrateHMDB
N Debenzoyl N tert butoxycarbonyl 10 deacetyltaxolMeSH
Chemical FormulaC43H53NO14
Average Molecular Weight807.8792
Monoisotopic Molecular Weight807.346605409
IUPAC Name(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetyloxy)-15-{[(2R,3S)-3-{[(tert-butoxy)carbonyl]amino}-2-hydroxy-3-phenylpropanoyl]oxy}-1,9,12-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl benzoate
Traditional Name(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetyloxy)-15-{[(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy}-1,9,12-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl benzoate
CAS Registry Number114977-28-5
SMILES
[H][C@@]12C[C@H](O)[C@@]3(C)C(=O)[C@H](O)C4=C(C)[C@H](C[C@@](O)([C@@H](OC(=O)C5=CC=CC=C5)[C@]3([H])[C@@]1(CO2)OC(C)=O)C4(C)C)OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C1=CC=CC=C1
InChI Identifier
InChI=1S/C43H53NO14/c1-22-26(55-37(51)32(48)30(24-15-11-9-12-16-24)44-38(52)58-39(3,4)5)20-43(53)35(56-36(50)25-17-13-10-14-18-25)33-41(8,34(49)31(47)29(22)40(43,6)7)27(46)19-28-42(33,21-54-28)57-23(2)45/h9-18,26-28,30-33,35,46-48,53H,19-21H2,1-8H3,(H,44,52)/t26-,27-,28+,30-,31+,32+,33-,35-,41+,42-,43+/m0/s1
InChI KeyZDZOTLJHXYCWBA-VCVYQWHSSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as taxanes and derivatives. These are diterpenoids with a structure based either on the taxane skeleton, or a derivative thereof. In term of phytochemistry, several derivatives of the taxane skeleton exist: 2(3->20)-abeotaxane, 3,11-cyclotaxane, 11(15->1),11(10->9)-abeotaxane, 3,8-seco-taxane, and 11(15->1)-abeotaxane, among others. More complex skeletons have been found recently, which include the taxane-derived [3.3.3] propellane ring system.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassDiterpenoids
Direct ParentTaxanes and derivatives
Alternative Parents
Substituents
  • Taxane diterpenoid
  • Benzoate ester
  • Benzoic acid or derivatives
  • Tricarboxylic acid or derivatives
  • Benzoyl
  • Fatty acid ester
  • Monocyclic benzene moiety
  • Fatty acyl
  • Monosaccharide
  • Benzenoid
  • Cyclic alcohol
  • Carbamic acid ester
  • Tertiary alcohol
  • Carboxylic acid ester
  • Ketone
  • Carbonic acid derivative
  • Oxetane
  • Secondary alcohol
  • Organoheterocyclic compound
  • Oxacycle
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Polyol
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Alcohol
  • Carbonyl group
  • Organic oxide
  • Organonitrogen compound
  • Organooxygen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

Biological role:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point232 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.013 g/LNot Available
LogP2.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.013 g/LALOGPS
logP2.59ALOGPS
logP2.92ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)10.96ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area224.45 ŲChemAxon
Rotatable Bond Count13ChemAxon
Refractivity203.9 m³·mol⁻¹ChemAxon
Polarizability82.15 ųChemAxon
Number of Rings6ChemAxon
BioavailabilityNoChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0ke9-2110021900-f5d0bc483676fe5dc3e1Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-056r-6520040900-5dc2943e6be89bc86b0cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a6r-6900660000-2867151287c5a0346e02Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-05iu-4410040920-b828ec76844ebea2d7a8Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-05i3-9210270300-f8577941b1621d9b82e5Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0ab9-9300140000-7ac14648b028058fac74Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue Locations
  • Kidney
  • Liver
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01248 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01248 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01248
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID130581
KEGG Compound IDC11231
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkDocetaxel
METLIN IDNot Available
PubChem Compound148124
PDB IDTXL
ChEBI ID4672
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Simons K, Toomre D: Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9. [PubMed:11413487 ]
  2. 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. [PubMed:16902246 ]
  3. 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. [PubMed:17374880 ]
  4. Lingwood D, Simons K: Lipid rafts as a membrane-organizing principle. Science. 2010 Jan 1;327(5961):46-50. doi: 10.1126/science.1174621. [PubMed:20044567 ]
  5. (). FDA label . .
  6. Gunstone, Frank D., John L. Harwood, and Albert J. Dijkstra (2007). The lipid handbook with CD-ROM. CRC Press.

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Participates in the metabolism of an as-yet-unknown biologically active molecule that is a participant in eye development.
Gene Name:
CYP1B1
Uniprot ID:
Q16678
Molecular weight:
60845.33
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular weight:
57108.065
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular weight:
57525.03
General function:
Involved in regulation of apoptosis
Specific function:
Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1)
Gene Name:
BCL2
Uniprot ID:
P10415
Molecular weight:
26265.7
References
  1. Gligorov J, Lotz JP: Preclinical pharmacology of the taxanes: implications of the differences. Oncologist. 2004;9 Suppl 2:3-8. [PubMed:15161985 ]
  2. Marshall J, Chen H, Yang D, Figueira M, Bouker KB, Ling Y, Lippman M, Frankel SR, Hayes DF: A phase I trial of a Bcl-2 antisense (G3139) and weekly docetaxel in patients with advanced breast cancer and other solid tumors. Ann Oncol. 2004 Aug;15(8):1274-83. [PubMed:15277270 ]
  3. Inoue Y, Gika M, Abiko T, Oyama T, Saitoh Y, Yamazaki H, Nakamura M, Abe Y, Kawamura M, Kobayashi K: Bcl-2 overexpression enhances in vitro sensitivity against docetaxel in non-small cell lung cancer. Oncol Rep. 2005 Feb;13(2):259-64. [PubMed:15643508 ]
  4. Petrylak DP: Chemotherapy for androgen-independent prostate cancer. World J Urol. 2005 Feb;23(1):10-3. Epub 2005 Feb 1. [PubMed:15685445 ]
  5. Miyoshi Y, Uemura H, Kubota Y: [Treatment of androgen-independent hormone refractory prostate cancer using docetaxel]. Nihon Rinsho. 2005 Feb;63(2):298-302. [PubMed:15714982 ]
  6. Magi-Galluzzi C, Zhou M, Reuther AM, Dreicer R, Klein EA: Neoadjuvant docetaxel treatment for locally advanced prostate cancer: a clinicopathologic study. Cancer. 2007 Sep 15;110(6):1248-54. [PubMed:17674353 ]
General function:
Involved in structural molecule activity
Specific function:
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha-chain
Gene Name:
TUBB1
Uniprot ID:
Q9H4B7
Molecular weight:
50326.6
References
  1. Gligorov J, Lotz JP: Preclinical pharmacology of the taxanes: implications of the differences. Oncologist. 2004;9 Suppl 2:3-8. [PubMed:15161985 ]
  2. Matesanz R, Barasoain I, Yang CG, Wang L, Li X, de Ines C, Coderch C, Gago F, Barbero JJ, Andreu JM, Fang WS, Diaz JF: Optimization of taxane binding to microtubules: binding affinity dissection and incremental construction of a high-affinity analog of paclitaxel. Chem Biol. 2008 Jun;15(6):573-85. doi: 10.1016/j.chembiol.2008.05.008. [PubMed:18559268 ]
  3. Snyder JP, Nettles JH, Cornett B, Downing KH, Nogales E: The binding conformation of Taxol in beta-tubulin: a model based on electron crystallographic density. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5312-6. Epub 2001 Apr 17. [PubMed:11309480 ]
  4. Belani CP, Eckardt J: Development of docetaxel in advanced non-small-cell lung cancer. Lung Cancer. 2004 Dec;46 Suppl 2:S3-11. [PubMed:15698529 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Wils P, Phung-Ba V, Warnery A, Lechardeur D, Raeissi S, Hidalgo IJ, Scherman D: Polarized transport of docetaxel and vinblastine mediated by P-glycoprotein in human intestinal epithelial cell monolayers. Biochem Pharmacol. 1994 Oct 7;48(7):1528-30. [PubMed:7945455 ]
  2. Shirakawa K, Takara K, Tanigawara Y, Aoyama N, Kasuga M, Komada F, Sakaeda T, Okumura K: Interaction of docetaxel ("Taxotere") with human P-glycoprotein. Jpn J Cancer Res. 1999 Dec;90(12):1380-6. [PubMed:10665657 ]