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Record Information
Version2.0
Creation Date2009-07-30 17:58:51 UTC
Update Date2014-12-24 20:26:07 UTC
Accession NumberT3D3501
Identification
Common NameDocetaxel
ClassSmall Molecule
DescriptionDocetaxel is a clinically well established anti-mitotic chemotherapy medication used mainly for the treatment of breast, ovarian, and non-small cell lung cancer. Docetaxel binds to microtubules reversibly with high affinity and has a maximum stoichiometry of one mole docetaxel per mole tubulin in microtubules.
Compound Type
  • Amine
  • Antimalarial
  • Antineoplastic Agent
  • Antineoplastic Agent, Phytogenic
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Radiation-Sensitizing Agent
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Docefrez
Docetaxel anhydrous
Docetaxel, Trihydrate
N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetylpaclitaxel
N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol
Taxotere
TXL
Chemical FormulaC43H53NO14
Average Molecular Mass807.879 g/mol
Monoisotopic Mass807.347 g/mol
CAS Registry Number114977-28-5
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
SMILES[H][C@](O)(C(=O)O[C@@]1([H])C[C@@]2(O)[C@@]([H])(OC(=O)C3=CC=CC=C3)[C@]3([H])[C@@]4(CO[C@]4([H])C[C@]([H])(O)[C@@]3(C)C(=O)[C@]([H])(O)C(=C1C)C2(C)C)OC(C)=O)[C@@]([H])(N=C(O)OC(C)(C)C)C1=CC=CC=C1
InChI IdentifierInChI=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 KeyInChIKey=ZDZOTLJHXYCWBA-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
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Kidney
  • Liver
Pathways
NameSMPDB LinkKEGG Link
Docetaxel PathwayNot AvailableNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point232°C
Boiling PointNot Available
SolubilityInsoluble
LogP2.4
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
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_5) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_6) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - 35V, Negativesplash10-0kmi-0069066000-3564c38332034a6ece44JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-056r-0597250110-87ceab2cb1907efad869JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-05iu-4410040920-b828ec76844ebea2d7a8JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-05i3-9210270300-f8577941b1621d9b82e5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0ab9-9300140000-7ac14648b028058fac74JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-3390000110-65c0d7adc2d422e11f9cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0pdi-5940101000-da55ca527881bac1ac24JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0059-9601000000-3666f54ffa6e69c8958aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0ke9-2110021900-f5d0bc483676fe5dc3e1JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-056r-6520040900-5dc2943e6be89bc86b0cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a6r-6900660000-2867151287c5a0346e02JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-003r-0390210310-072c630f13bc0f81269aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-1590201200-973eb03969da7056a8a6JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0abc-3910101210-42478cd96d93fb415eebJSpectraViewer
Toxicity Profile
Route of ExposureIntravenous injection. The pharmacokinetic profile is consistent with a three-compartment model. The area under the curve (AUC) was dose proportional following doses of 70 mg/m2 to 115 mg/m2 with infusion times of 1 to 2 hours.
Mechanism of ToxicityDocetaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, docetaxel 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, docetaxel binds to the β-subunit of tubulin. Tubulin is the 'building block' of mictotubules, and the binding of docetaxel locks these building blocks in place. The resulting microtubule/docetaxel 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 docetaxel 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 drug interaction studies revealed that docetaxel is metabolized by the CYP3A4 isoenzyme (1 major, 3 minor metabolites). Route of Elimination: Docetaxel was eliminated in both the urine and feces following oxidative metabolism of the tert-butyl ester group, but fecal excretion was the main elimination route. Within 7 days, urinary and fecal excretion accounted for approximately 6% and 75% of the administered radioactivity, respectively. Half Life: Dose-dependent. Doses of 70 mg per square meter of body surface area (mg/m 2 ) or higher produce a triphasic elimination profile. With lower doses, assay limitations precluded detection of the terminal elimination phase. The half-life of the alpha, beta, and gamma phase are 4 minutes, 36 minutes, and 11.1 hours, respectively.
Toxicity ValuesOral LD50 in rat is >2000 mg/kg.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Also used as a single agent in the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. It is also used in combination with prednisone, in the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer. Furthermore, docetaxel has uses in the treatment of gastric adenocarinoma and head and neck cancer.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsAnticipated complications of overdosage include: bone marrow suppression, peripheral neurotoxicity, and mucositis. In two reports of overdose, one patient received 150 mg/m2 and the other received 200 mg/m2 as 1-hour infusions. Both patients experienced severe neutropenia, mild asthenia, cutaneous reactions, and mild paresthesia, and recovered without incident.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01248
HMDB IDHMDB15378
PubChem Compound ID148124
ChEMBL IDCHEMBL92
ChemSpider ID130581
KEGG IDC11231
UniProt IDNot Available
OMIM ID
ChEBI ID4672
BioCyc IDNot Available
CTD IDNot Available
Stitch IDDocetaxel
PDB IDTXL
ACToR IDNot Available
Wikipedia LinkDocetaxel
References
Synthesis Reference

Nicholas J. Sisti, Charles S. Swindell, “Method for docetaxel synthesis.” U.S. Patent US5688977, issued September, 1991.

MSDSLink
General References
  1. FDA label
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
References
  1. Ikezoe T, Hisatake Y, Takeuchi T, Ohtsuki Y, Yang Y, Said JW, Taguchi H, Koeffler HP: HIV-1 protease inhibitor, ritonavir: a potent inhibitor of CYP3A4, enhanced the anticancer effects of docetaxel in androgen-independent prostate cancer cells in vitro and in vivo. Cancer Res. 2004 Oct 15;64(20):7426-31. [15492266 ]
  2. Harmsen S, Meijerman I, Beijnen JH, Schellens JH: Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor. Cancer Chemother Pharmacol. 2009 Jun;64(1):35-43. doi: 10.1007/s00280-008-0842-3. Epub 2008 Oct 7. [18839173 ]
General Function:
Ubiquitin protein ligase binding
Specific Function:
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.Isoform 2 may act as an antagonist of EGF action.
Gene Name:
EGFR
Uniprot ID:
P00533
Molecular Weight:
134276.185 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation0.00082 uMNot AvailableBindingDB 36351
References
  1. Buchholz S, Schally AV, Engel JB, Hohla F, Heinrich E, Koester F, Varga JL, Halmos G: Potentiation of mammary cancer inhibition by combination of antagonists of growth hormone-releasing hormone with docetaxel. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1943-6. Epub 2007 Jan 29. [17261802 ]
General Function:
Peptide hormone binding
Specific Function:
Receptor for GRF, coupled to G proteins which activate adenylyl cyclase. Stimulates somatotroph cell growth, growth hormone gene transcription and growth hormone secretion.
Gene Name:
GHRHR
Uniprot ID:
Q02643
Molecular Weight:
47401.53 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.00014 uMNot AvailableBindingDB 36351
References
  1. Buchholz S, Schally AV, Engel JB, Hohla F, Heinrich E, Koester F, Varga JL, Halmos G: Potentiation of mammary cancer inhibition by combination of antagonists of growth hormone-releasing hormone with docetaxel. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1943-6. Epub 2007 Jan 29. [17261802 ]
General Function:
Protein kinase binding
Specific Function:
Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.
Gene Name:
KIF11
Uniprot ID:
P52732
Molecular Weight:
119158.025 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.00018 uMNot AvailableBindingDB 36351
IC500.0003 uMNot AvailableBindingDB 36351
IC500.00031 uMNot AvailableBindingDB 36351
IC500.0087 uMNot AvailableBindingDB 36351
References
  1. Luo L, Parrish CA, Nevins N, McNulty DE, Chaudhari AM, Carson JD, Sudakin V, Shaw AN, Lehr R, Zhao H, Sweitzer S, Lad L, Wood KW, Sakowicz R, Annan RS, Huang PS, Jackson JR, Dhanak D, Copeland RA, Auger KR: ATP-competitive inhibitors of the mitotic kinesin KSP that function via an allosteric mechanism. Nat Chem Biol. 2007 Nov;3(11):722-6. Epub 2007 Oct 7. [17922005 ]
General Function:
Structural molecule activity
Specific Function:
The exact function of MAP2 is unknown but MAPs may stabilize the microtubules against depolymerization. They also seem to have a stiffening effect on microtubules.
Gene Name:
MAP2
Uniprot ID:
P11137
Molecular Weight:
199524.51 Da
References
  1. McGrogan BT, Gilmartin B, Carney DN, McCann A: Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta. 2008 Apr;1785(2):96-132. Epub 2007 Nov 12. [18068131 ]
General Function:
Structural molecule activity
Specific Function:
Non-neuronal microtubule-associated protein. Promotes microtubule assembly.
Gene Name:
MAP4
Uniprot ID:
P27816
Molecular Weight:
121003.805 Da
References
  1. McGrogan BT, Gilmartin B, Carney DN, McCann A: Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta. 2008 Apr;1785(2):96-132. Epub 2007 Nov 12. [18068131 ]
General Function:
Structural constituent of cytoskeleton
Specific Function:
Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both. Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization.
Gene Name:
MAPT
Uniprot ID:
P10636
Molecular Weight:
78927.025 Da
References
  1. McGrogan BT, Gilmartin B, Carney DN, McCann A: Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta. 2008 Apr;1785(2):96-132. Epub 2007 Nov 12. [18068131 ]
General Function:
Ubiquitin protein ligase binding
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). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).
Gene Name:
BCL2
Uniprot ID:
P10415
Molecular Weight:
26265.66 Da
General Function:
Structural constituent of cytoskeleton
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 (By similarity).
Gene Name:
TUBB1
Uniprot ID:
Q9H4B7
Molecular Weight:
50326.56 Da