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Identification
NameDocetaxel
Accession NumberDB01248  (APRD00932)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Docetaxel 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.

Structure
Thumb
Synonyms
Docetaxel anhydrous
N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetylpaclitaxel
N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol
TXL
External Identifiers
  • RP-6976
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DocefrezkitSun Pharma Global FZE2011-05-03Not applicableUs
Docetaxelinjection, solution20 mg/mLintravenousNorthstar Rx LLC2016-01-01Not applicableUs
Docetaxelinjection, solution, concentrate20 mg/2mLintravenousPfizer Laboratories Div Pfizer Inc2014-06-23Not applicableUs
Docetaxelinjection, solution20 mg/mLintravenousMc Kesson Packaging Services A Business Unit Of Mc Kesson Corporation2011-06-08Not applicableUs
Docetaxelinjection, solution, concentrate20 mg/mLintravenousActavis Pharma, Inc.2015-10-13Not applicableUs
Docetaxelinjection, solution, concentrate80 mg/4mLintravenousWinthrop U.S.2010-10-21Not applicableUs
Docetaxelinjection, solution, concentrate20 mg/mLintravenousAccord Healthcare Inc.2013-05-15Not applicableUs
Docetaxelinjection, solution, concentrate20 mg/mLintravenousActavis Pharma, Inc.2014-09-01Not applicableUs
Docetaxelinjection, solution, concentrate20 mg/mLintravenousWinthrop U.S.2010-10-21Not applicableUs
Docetaxelinjection, solution, concentrate20 mg/mLintravenousAccord Healthcare Inc.2012-07-01Not applicableUs
Docetaxelinjection, solution, concentrate20 mg/mLintravenousActavis Pharma, Inc.2014-09-01Not applicableUs
Docetaxelinjection, solution10 mg/mLintravenousHospira, Inc.2011-03-08Not applicableUs
Docetaxelinjection, solution, concentrate20 mg/mLintravenousActavis Pharma, Inc.2014-09-01Not applicableUs
DocetaxelkitAccord Healthcare Inc.2011-06-30Not applicableUs
Docetaxelinjection, solution10 mg/mLintravenousSandoz Inc2015-07-22Not applicableUs
DocetaxelkitAccord Healthcare Inc.2011-06-30Not applicableUs
Docetaxelinjection, solution, concentrate200 mg/20mLintravenousPfizer Laboratories Div Pfizer Inc2014-06-23Not applicableUs
Docetaxelinjection, solution10 mg/mLintravenousSandoz Inc2011-06-29Not applicableUs
Docetaxelinjection, solution80 mg/4mLintravenousNorthstar Rx LLC2016-01-01Not applicableUs
Docetaxelinjection, solution, concentrate80 mg/8mLintravenousPfizer Laboratories Div Pfizer Inc2014-06-23Not applicableUs
Docetaxelinjection, solution20 mg/mLintravenousMc Kesson Packaging Services A Business Unit Of Mc Kesson Corporation2011-06-08Not applicableUs
Docetaxel for Injectionsolution10.0 mgintravenousHospira Healthcare Corporation2011-03-01Not applicableCanada
Docetaxel Injectionsolution20 mgintravenousTeva Canada Limited2014-03-28Not applicableCanada
Docetaxel Injectionsolution10 mgintravenousSandoz Canada IncorporatedNot applicableNot applicableCanada
Docetaxel Injectionsolution20 mgintravenousAccord Healthcare Inc2015-02-27Not applicableCanada
Docetaxel Injectionsolution80 mgintravenousTeva Canada Limited2014-03-28Not applicableCanada
Docetaxel Non-alcohol Formulainjection20 mg/mLintravenousEagle Pharmaceuticals, Inc.2016-01-15Not applicableUs
PMS-docetaxelsolution; kit80 mgintravenousPharmascience IncNot applicableNot applicableCanada
PMS-docetaxelsolution; kit20 mgintravenousPharmascience IncNot applicableNot applicableCanada
Taxoteresolution80 mgintravenousSanofi Aventis Canada Inc1995-12-31Not applicableCanada
Taxoteresolution20 mgintravenousSanofi Aventis Canada Inc1995-12-31Not applicableCanada
Taxotereinjection, solution, concentrate80 mg/4mLintravenousSanofi Aventis U.S. Llc2010-08-02Not applicableUs
Taxotereinjection, solution, concentrate20 mg/mLintravenousSanofi Aventis U.S. Llc2010-08-02Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Docetaxelinjection, solution, concentrate20 mg/mLintravenousTeva Parenteral Medicines, Inc.2015-12-31Not applicableUs
Docetaxelinjection, solution20 mg/mLintravenousDr. Reddy's Laboratories Inc.2014-11-10Not applicableUs
Docetaxelinjection, solution20 mg/mLintravenousDr. Reddy's Laboratories Inc.2014-11-10Not applicableUs
Docetaxelsolution20 mg/mLintravenousSagent Pharmaceuticals2013-07-01Not applicableUs
Docetaxelinjection, solution, concentrate80 mg/4mLintravenousTeva Parenteral Medicines, Inc.2015-12-31Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Docetaxel trihydrate
148408-66-6
Thumb
  • InChI Key: XCDIRYDKECHIPE-QHEQPUDQSA-N
  • Monoisotopic Mass: 861.378299444
  • Average Mass: 861.935
DBSALT001786
Categories
UNII699121PHCA
CAS number114977-28-5
WeightAverage: 807.8792
Monoisotopic: 807.346605409
Chemical FormulaC43H53NO14
InChI KeyInChIKey=ZDZOTLJHXYCWBA-VCVYQWHSSA-N
InChI
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
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[11.3.1.0³,¹⁰.0⁴,⁷]heptadec-13-en-2-yl benzoate
SMILES
[H][C@@]12C[[email protected]](O)[C@@]3(C)C(=O)[[email protected]](O)C4=C(C)[[email protected]](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)[[email protected]](O)[C@@H](NC(=O)OC(C)(C)C)C1=CC=CC=C1
Taxonomy
DescriptionThis compound 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
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassDiterpenoids
Direct ParentTaxanes and derivatives
Alternative Parents
Substituents
  • Taxane diterpenoid
  • Phenylpropylamine
  • Benzoate ester
  • Tricarboxylic acid or derivatives
  • Benzylether
  • Benzoic acid or derivatives
  • Benzoyl
  • Fatty acid ester
  • Fatty acyl
  • Benzenoid
  • Monosaccharide
  • Monocyclic benzene moiety
  • Acetate salt
  • Tertiary alcohol
  • Cyclic alcohol
  • Secondary alcohol
  • Polyol
  • Oxetane
  • Ketone
  • Carboxylic acid ester
  • Oxacycle
  • Organoheterocyclic compound
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsDocetaxel is a taxoid antineoplastic agent. It 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, docetaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.
Mechanism of actionDocetaxel 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.
Related Articles
AbsorptionThe 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.
Volume of distribution

The initial rapid decline represents distribution to the peripheral compartments and the late (terminal) phase is due, in part, to a relatively slow efflux of docetaxel from the peripheral compartment.

  • 113 L
Protein bindingIn vitro studies show that 94% protein bound, mainly to a1-acid glycoprotein, albumin, and lipoproteins. When measured in cancer patients, docetaxel is 97% bound to plasma protein. Dexamethasone does not affect the protein binding of docetaxel.
Metabolism

Hepatic. In vitro drug interaction studies revealed that docetaxel is metabolized by the CYP3A4 isoenzyme (1 major, 3 minor metabolites).

Route of eliminationDocetaxel 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 lifeDose-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.
Clearance
  • 21 L/h/m2 [Total body clearance, cancer patients after IV administration of 20–115 mg/m2]
ToxicityOral LD50 in rat is >2000 mg/kg. Anticipated 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.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Docetaxel Action PathwayDrug actionSMP00435
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Canalicular multispecific organic anion transporter 1
Gene symbol: ABCC2
UniProt: Q92887
rs12762549 Not AvailableG AlleleLeukopenia, neutropenia18294295
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9743
Blood Brain Barrier-0.9659
Caco-2 permeable-0.8252
P-glycoprotein substrateSubstrate0.8259
P-glycoprotein inhibitor IInhibitor0.644
P-glycoprotein inhibitor IINon-inhibitor0.5139
Renal organic cation transporterNon-inhibitor0.9393
CYP450 2C9 substrateNon-substrate0.816
CYP450 2D6 substrateNon-substrate0.8828
CYP450 3A4 substrateSubstrate0.7119
CYP450 1A2 substrateNon-inhibitor0.8299
CYP450 2C9 inhibitorNon-inhibitor0.8737
CYP450 2D6 inhibitorNon-inhibitor0.8972
CYP450 2C19 inhibitorNon-inhibitor0.8421
CYP450 3A4 inhibitorNon-inhibitor0.7324
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8776
Ames testNon AMES toxic0.8382
CarcinogenicityNon-carcinogens0.9133
BiodegradationNot ready biodegradable0.9934
Rat acute toxicity2.5741 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9907
hERG inhibition (predictor II)Non-inhibitor0.7905
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Injection, solutionintravenous10 mg/mL
Injection, solutionintravenous20 mg/mL
Injection, solutionintravenous80 mg/4mL
Injection, solution, concentrateintravenous20 mg/2mL
Injection, solution, concentrateintravenous200 mg/20mL
Injection, solution, concentrateintravenous80 mg/8mL
Kit
Solutionintravenous20 mg/mL
Solutionintravenous10.0 mg
Solutionintravenous10 mg
Injectionintravenous20 mg/mL
Solution; kitintravenous20 mg
Solution; kitintravenous80 mg
Injection, solution, concentrateintravenous20 mg/mL
Injection, solution, concentrateintravenous80 mg/4mL
Solutionintravenous20 mg
Solutionintravenous80 mg
Prices
Unit descriptionCostUnit
Taxotere 20 mg/0.5 ml vial477.37USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2149055 No2003-01-072013-11-08Canada
CA2150576 No2005-06-212013-11-26Canada
US4814470 No1993-05-142010-05-14Us
US5438072 No1994-05-222014-05-22Us
US8940786 No2013-09-302033-09-30Us
US9308195 No2013-09-302033-09-30Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point232 °CPhysProp
water solubilityInsoluble FDA label
logP2.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0127 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity203.9 m3·mol-1ChemAxon
Polarizability82.06 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

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

US5688977
General ReferencesNot Available
External Links
ATC CodesL01CD02
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelDownload (140 KB)
MSDSDownload (100 KB)
Interactions
Drug Interactions
Drug
BexaroteneThe serum concentration of Docetaxel can be decreased when it is combined with Bexarotene.
BosentanThe serum concentration of Docetaxel can be decreased when it is combined with Bosentan.
CisplatinCisplatin may increase the myelosuppressive activities of Docetaxel.
ClozapineThe risk or severity of adverse effects can be increased when Docetaxel is combined with Clozapine.
ConivaptanThe serum concentration of Docetaxel can be increased when it is combined with Conivaptan.
DabrafenibThe serum concentration of Docetaxel can be decreased when it is combined with Dabrafenib.
DasatinibThe serum concentration of Docetaxel can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Docetaxel can be decreased when it is combined with Deferasirox.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Docetaxel.
DronedaroneThe serum concentration of Docetaxel can be increased when it is combined with Dronedarone.
FluconazoleThe metabolism of Docetaxel can be decreased when combined with Fluconazole.
Fusidic AcidThe serum concentration of Docetaxel can be increased when it is combined with Fusidic Acid.
IdelalisibThe serum concentration of Docetaxel can be increased when it is combined with Idelalisib.
ItraconazoleThe metabolism of Docetaxel can be decreased when combined with Itraconazole.
IvacaftorThe serum concentration of Docetaxel can be increased when it is combined with Ivacaftor.
KetoconazoleThe metabolism of Docetaxel can be decreased when combined with Ketoconazole.
LeflunomideThe risk or severity of adverse effects can be increased when Docetaxel is combined with Leflunomide.
LuliconazoleThe serum concentration of Docetaxel can be increased when it is combined with Luliconazole.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Docetaxel.
MifepristoneThe serum concentration of Docetaxel can be increased when it is combined with Mifepristone.
MitotaneThe serum concentration of Docetaxel can be decreased when it is combined with Mitotane.
MitoxantroneThe risk or severity of adverse effects can be increased when Docetaxel is combined with Mitoxantrone.
NatalizumabThe risk or severity of adverse effects can be increased when Docetaxel is combined with Natalizumab.
NelfinavirThe metabolism of Docetaxel can be decreased when combined with Nelfinavir.
NetupitantThe serum concentration of Docetaxel can be increased when it is combined with Netupitant.
PalbociclibThe serum concentration of Docetaxel can be increased when it is combined with Palbociclib.
PhenytoinThe metabolism of Docetaxel can be increased when combined with Phenytoin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Docetaxel.
PosaconazoleThe metabolism of Docetaxel can be decreased when combined with Posaconazole.
RanolazineThe serum concentration of Docetaxel can be increased when it is combined with Ranolazine.
RoflumilastRoflumilast may increase the immunosuppressive activities of Docetaxel.
SaquinavirThe serum concentration of Docetaxel can be increased when it is combined with Saquinavir.
SiltuximabThe serum concentration of Docetaxel can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Docetaxel can be increased when it is combined with Simeprevir.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Docetaxel.
SorafenibThe serum concentration of Docetaxel can be increased when it is combined with Sorafenib.
St. John's WortThe serum concentration of Docetaxel can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Docetaxel can be increased when it is combined with Stiripentol.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Docetaxel.
TesmilifeneThe serum concentration of Docetaxel can be decreased when it is combined with Tesmilifene.
TocilizumabThe serum concentration of Docetaxel can be decreased when it is combined with Tocilizumab.
TofacitinibDocetaxel may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Docetaxel.
VerapamilThe serum concentration of Docetaxel can be increased when it is combined with Verapamil.
VoriconazoleThe metabolism of Docetaxel can be decreased when combined with Voriconazole.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
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
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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 f...
Gene Name:
BCL2
Uniprot ID:
P10415
Molecular Weight:
26265.66 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
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. [PubMed:18068131 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
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. [PubMed:18068131 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
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 ce...
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. [PubMed:18068131 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
binder
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 is...
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. [PubMed:15492266 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Vitamin d3 25-hydroxylase 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 xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
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 ]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
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 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
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 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitorinducer
General Function:
Oxygen binding
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, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compou...
Gene Name:
CYP1B1
Uniprot ID:
Q16678
Molecular Weight:
60845.33 Da
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 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Atpase activity, coupled to transmembrane movement of substances
Specific Function:
ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
Gene Name:
ABCC10
Uniprot ID:
Q5T3U5
Molecular Weight:
161627.375 Da
References
  1. Hopper-Borge E, Xu X, Shen T, Shi Z, Chen ZS, Kruh GD: Human multidrug resistance protein 7 (ABCC10) is a resistance factor for nucleoside analogues and epothilone B. Cancer Res. 2009 Jan 1;69(1):178-84. doi: 10.1158/0008-5472.CAN-08-1420. [PubMed:19118001 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotrexate and sulfobromophthalein (BSP). Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B3
Uniprot ID:
Q9NPD5
Molecular Weight:
77402.175 Da
References
  1. Baker SD, Verweij J, Cusatis GA, van Schaik RH, Marsh S, Orwick SJ, Franke RM, Hu S, Schuetz EG, Lamba V, Messersmith WA, Wolff AC, Carducci MA, Sparreboom A: Pharmacogenetic pathway analysis of docetaxel elimination. Clin Pharmacol Ther. 2009 Feb;85(2):155-63. doi: 10.1038/clpt.2008.95. Epub 2008 May 28. [PubMed:18509327 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha-ketoglutarate.
Gene Name:
SLC22A7
Uniprot ID:
Q9Y694
Molecular Weight:
60025.025 Da
References
  1. Kobayashi Y, Ohshiro N, Sakai R, Ohbayashi M, Kohyama N, Yamamoto T: Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]). J Pharm Pharmacol. 2005 May;57(5):573-8. [PubMed:15901346 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. Fellner S, Bauer B, Miller DS, Schaffrik M, Fankhanel M, Spruss T, Bernhardt G, Graeff C, Farber L, Gschaidmeier H, Buschauer A, Fricker G: Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo. J Clin Invest. 2002 Nov;110(9):1309-18. [PubMed:12417570 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Organic anion transmembrane transporter activity
Specific Function:
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name:
ABCC2
Uniprot ID:
Q92887
Molecular Weight:
174205.64 Da
References
  1. Fellner S, Bauer B, Miller DS, Schaffrik M, Fankhanel M, Spruss T, Bernhardt G, Graeff C, Farber L, Gschaidmeier H, Buschauer A, Fricker G: Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo. J Clin Invest. 2002 Nov;110(9):1309-18. [PubMed:12417570 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Transporter activity
Specific Function:
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency.
Gene Name:
ABCC1
Uniprot ID:
P33527
Molecular Weight:
171589.5 Da
References
  1. Fellner S, Bauer B, Miller DS, Schaffrik M, Fankhanel M, Spruss T, Bernhardt G, Graeff C, Farber L, Gschaidmeier H, Buschauer A, Fricker G: Transport of paclitaxel (Taxol) across the blood-brain barrier in vitro and in vivo. J Clin Invest. 2002 Nov;110(9):1309-18. [PubMed:12417570 ]
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Drug created on June 13, 2005 07:24 / Updated on June 28, 2016 02:49