Docetaxel

Identification

Summary

Docetaxel is a taxoid antineoplastic agent used in the treatment of various cancers, such as locally advanced or metastatic breast cancer, metastatic prostate cancer, gastric adenocarcinoma, and head and neck cancer.

Brand Names
Taxotere
Generic Name
Docetaxel
DrugBank Accession Number
DB01248
Background

Docetaxel is a clinically well established anti-mitotic chemotherapy medication used for the treatment of different types of cancer, including breast, ovarian, and non-small cell lung cancer. Docetaxel is a complex diterpenoid molecule and a semisynthetic analogue of paclitaxel.6,7 Docetaxel reversibly binds to microtubulin with high affinity in a 1:1 stoichiometric ratio, allowing it to prevent cell division and promote to cell death.6 Compared to paclitaxel, docetaxel is two times more potent as an inhibitor of microtubule depolymerization. Docetaxel binds to microtubules but does not interact with dimeric tubulin.5

The use of docetaxel may lead to udesired outcomes such as hepatic impairment, hematologic effects, enterocolitis and neutropenic colitis, hypersensitivity reactions, fluid retention, second primary malignancies, embryo-fetal toxicity, and tumor lysis syndrome.7 Docetaxel was approved by the FDA in 1996 and is available in solution for injection for intravenous or parenteral administration.6

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 807.8792
Monoisotopic: 807.346605409
Chemical Formula
C43H53NO14
Synonyms
  • Docetaxel
  • Docetaxel anhydrous
  • N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetylpaclitaxel
  • N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol
  • TXL
External IDs
  • CKD-810
  • RP-6976

Pharmacology

Indication

Docetaxel is indicated as a single agent for the treatment of locally advanced or metastatic breast cancer after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive BC. It is also indicated as a single agent for locally advanced or metastatic non-small cell lung cancer (NSCLC) after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated NSCLC. For the treatment of metastatic castration-resistant prostate cancer, docetaxel is indicated with prednisone. Docetaxel is also indicated with cisplatin and fluorouracil for untreated, advanced gastric adenocarcinoma, including the gastroesophageal junction, and with cisplatin and fluorouracil for induction treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN).7

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofEsophageal cancer••• •••••
Treatment ofLocally advanced breast cancer••••••••••••
Treatment ofMetastatic bladder cancer••• •••••
Treatment ofMetastatic breast cancer••••••••••••
Used in combination to treatMetastatic hormone refractory prostate cancerRegimen in combination with: Prednisone (DB00635)••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Docetaxel 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 which 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.4,5

The use of docetaxel may lead to treatment-related deaths in breast cancer and non-small cell lung cancer patients, hepatic impairment, hematologic effects, enterocolitis and neutropenic colitis, hypersensitivity reactions, fluid retention, second primary malignancies, cutaneous reactions, neurologic reactions, eye disorders, asthenia, embryo-fetal toxicity, and tumor lysis syndrome.7

Mechanism of action

Docetaxel 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 microtubules, 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), thus arresting its function.4,5,7

TargetActionsOrganism
ATubulin beta-1 chainNot AvailableHumans
AMicrotubule-associated protein 2Not AvailableHumans
AMicrotubule-associated protein 4Not AvailableHumans
AMicrotubule-associated protein tauNot AvailableHumans
UApoptosis regulator Bcl-2Not AvailableHumans
UNuclear receptor subfamily 1 group I member 2
binder
Humans
Absorption

The pharmacokinetic profile of docetaxel is consistent with a three-compartment model. The initial rapid decline represents the distribution to the peripheral compartments, and the late (terminal) phase is partly due to a relatively slow efflux of docetaxel from the peripheral compartment. The area under the curve (AUC) was dose proportional at doses between 70 mg/m2 and 115 mg/m2 with infusion times of 1 to 2 hours.7,9 In a group of patients with solid tumors given 100 mg/m2 of docetaxel intravenously, the Cmax and AUC were 2.41 μg/mL and 5.93 μg⋅h/mL, respectively.1,3

Volume of distribution

Docetaxel has a steady-state volume of distribution of 113 L. Its pharmacokinetic profile is consistent with a three-compartment pharmacokinetic model.7,9

Protein binding

In vitro studies show that 94% of docetaxel is bound to proteins, mainly alpha-1-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.7,9

Metabolism

Docetaxel undergoes hepatic metabolism. In vitro drug interaction studies revealed that docetaxel is metabolized by the CYP3A4 isoenzyme.7,9 CYP3A5 also plays a role in the metabolism of this drug.1 In humans, docetaxel is metabolized by CYP3A4/5 into four metabolites: M1, M2, M3 and M4. Docetaxel undergoes hydroxylation of the synthetic isobutoxy side chain, forming metabolite M2. The oxidation of M2 forms an unstable aldehyde that is immediately cyclised into the stereoisomers M1 and M3. M4 is then formed by the oxidation of M1/M3.2

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Route of elimination

Docetaxel was eliminated in 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. In the first 48 hours, approximately 80% of the radioactivity recovered was excreted in feces. One major and three minor metabolites were excreted at this point, with less than 8% as the unchanged drug.7,9

Half-life

With plasma sampling up to 8 to 22 days after docetaxel infusion, the terminal elimination half-life was 116 hours.7 Doses between 70 and 115 mg/m2 with infusion times of 1 to 2 hours produce a triphasic elimination profile. The half-life of the alpha, beta, and gamma phases are 4 minutes, 36 minutes, and 11.1 hours, respectively.9

Clearance

After the administration of 20–115 mg/m2 of intravenous docetaxel to cancer patients, the total body clearance was 21 L/h/m2.9 In patients aged 1 to 20 years with solid tumors that received 55 mg/m2 to 235 mg/m2 of docetaxel in a 1-hour intravenous infusion every 3 weeks, clearance was 17.3 L/h/m2.7

Adverse Effects
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Toxicity

There is no known antidote for an overdose of docetaxel injection. In case of overdose, patients should be closely monitored in specialized units. Some of the anticipated complications of overdosage include: bone marrow suppression, peripheral neurotoxicity, and mucositis. After an overdose is discovered, patients should receive granulocyte colony-stimulating factor (G-CSF) as soon as possible. Other appropriate symptomatic measures should be taken as needed.7

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.7 In rats, the oral LD50 of docetaxel is >2000 mg/kg. The intravenous LD50 in mice is 138 mg/kg.8

Pathways
PathwayCategory
Docetaxel Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Canalicular multispecific organic anion transporter 1---(G;G) / (C;G)G AlleleADR Directly StudiedPatients with this polymorphism in ABCC2 are at a higher risk of experiencing drug-induced leukopenia and drug-induced neutropenia when treated with docetaxel.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Docetaxel can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Docetaxel can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Docetaxel.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Docetaxel.
AcalabrutinibThe metabolism of Docetaxel can be decreased when combined with Acalabrutinib.
Food Interactions
  • Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum levels of docetaxel.
  • Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of docetaxel.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Docetaxel trihydrate15H5577CQD148408-66-6XCDIRYDKECHIPE-QHEQPUDQSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act Docetaxel 40 mg/mlSolution80 mg / 2 mLIntravenousActavis Pharma CompanyNot applicableNot applicableCanada flag
Act Docetaxel 40 mg/mlSolution20 mg / 0.5 mLIntravenousActavis Pharma CompanyNot applicableNot applicableCanada flag
DocefrezKit20 mg/0.8mLIntravenousSun Pharma Global FZE2011-05-032016-12-31US flag
DocefrezKit80 mg/4mLIntravenousSun Pharma Global FZE2011-05-032011-08-10US flag
DocetaxelInjection, solution20 mg/1mLIntravenousHospira, Inc.2021-06-28Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DocetaxelInjection, solution, concentrate20 mg/1mLIntravenousX-GEN Pharmaceuticals, Inc.2017-04-17Not applicableUS flag
DocetaxelInjection10 mg/1mLIntravenousAlembic Pharmaceuticals Limited2023-02-28Not applicableUS flag
DocetaxelInjection, solution, concentrate80 mg/4mLIntravenousWinthrop U.S, a business of sanofi-aventis U.S. LLC2010-10-21Not applicableUS flag
DocetaxelInjection80 mg/4mLIntravenousArmas Pharmaceuticals Inc.2020-01-15Not applicableUS flag
DocetaxelInjection, solution10 mg/1mLIntravenousMylan Institutional LLC2022-08-03Not applicableUS flag

Categories

ATC Codes
L01CD02 — Docetaxel
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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: 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.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Diterpenoids
Direct Parent
Taxanes and derivatives
Alternative Parents
Benzoic acid esters / Tricarboxylic acids and derivatives / Benzoyl derivatives / Fatty acid esters / Monosaccharides / Tertiary alcohols / Carbamate esters / Secondary alcohols / Oxetanes / Carboxylic acid esters
show 10 more
Substituents
Alcohol / Aromatic heteropolycyclic compound / Benzenoid / Benzoate ester / Benzoic acid or derivatives / Benzoyl / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Carboxylic acid derivative
show 24 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tetracyclic diterpenoid (CHEBI:4672)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
699121PHCA
CAS number
114977-28-5
InChI Key
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[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl benzoate
SMILES
[H][C@@]1(C[C@@]2(O)[C@@H](OC(=O)C3=CC=CC=C3)[C@]3([H])[C@@]4(CO[C@@H]4C[C@H](O)[C@@]3(C)C(=O)[C@H](O)C(=C1C)C2(C)C)OC(C)=O)OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C1=CC=CC=C1

References

Synthesis Reference

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

US5688977
General References
  1. Kenmotsu H, Tanigawara Y: Pharmacokinetics, dynamics and toxicity of docetaxel: Why the Japanese dose differs from the Western dose. Cancer Sci. 2015 May;106(5):497-504. doi: 10.1111/cas.12647. Epub 2015 Mar 25. [Article]
  2. Hendrikx JJ, Dubbelman AC, Rosing H, Schinkel AH, Schellens JH, Beijnen JH: Quantification of docetaxel and its metabolites in human plasma by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2013 Sep 15;27(17):1925-34. doi: 10.1002/rcm.6654. [Article]
  3. Extra JM, Rousseau F, Bruno R, Clavel M, Le Bail N, Marty M: Phase I and pharmacokinetic study of Taxotere (RP 56976; NSC 628503) given as a short intravenous infusion. Cancer Res. 1993 Mar 1;53(5):1037-42. [Article]
  4. Pienta KJ: Preclinical mechanisms of action of docetaxel and docetaxel combinations in prostate cancer. Semin Oncol. 2001 Aug;28(4 Suppl 15):3-7. doi: 10.1016/s0093-7754(01)90148-4. [Article]
  5. Bissery MC, Nohynek G, Sanderink GJ, Lavelle F: Docetaxel (Taxotere): a review of preclinical and clinical experience. Part I: Preclinical experience. Anticancer Drugs. 1995 Jun;6(3):339-55, 363-8. doi: 10.1097/00001813-199506000-00001. [Article]
  6. Authors unspecified: Docetaxel. . [Article]
  7. FDA Approved Drug Products: DOCETAXEL injection for intravenous use (May 2023) [Link]
  8. Pfizer: Docetaxel Injection SDS [Link]
  9. FDA Approved Drug Products: TAXOTERE (docetaxel) for injection concentrate (December 1999) [Link]
Human Metabolome Database
HMDB0015378
KEGG Drug
D02165
KEGG Compound
C11231
PubChem Compound
148124
PubChem Substance
46506766
ChemSpider
130581
BindingDB
36351
RxNav
1299922
ChEBI
4672
ChEMBL
CHEMBL92
ZINC
ZINC000085537053
Therapeutic Targets Database
DAP000590
PharmGKB
PA449383
PDBe Ligand
TXL
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Docetaxel
PDB Entries
1ia0 / 1tub

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedDiagnosticBreast Cancer1
4CompletedHealth Services ResearchBreast Cancer1
4CompletedTreatmentBreast Cancer5
4CompletedTreatmentBreast Cancer / Female Breast Cancer1
4CompletedTreatmentBreast Neoplasms1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Sanofi-Aventis Inc.
Dosage Forms
FormRouteStrength
InjectionParenteral20 mg
SolutionIntramuscular21.338 mg
SolutionIntravenous20.00 mg
Injection
Solution / dropsOphthalmic2 MG/ML
Injection, solution, concentrateIntravenous40 mg/ml
SolutionIntravenous20.000 mg
Solution20 mg/1ml
Injection, solution, concentrateIntravenous20.0 mg/ml
InjectionIntravenous40 mg/ml
KitIntravenous20 mg/0.8mL
KitIntravenous80 mg/4mL
PowderIntravenous
InjectionIntravenous20 mg/ml
InjectionIntravenous80 mg/ml
InjectionIntravenous10 mg/1mL
InjectionIntravenous160 mg/8mL
InjectionIntravenous80 mg/4mL
Injection, solutionIntravenous10 mg/1mL
Injection, solutionIntravenous160 mg/8mL
Injection, solutionIntravenous20 mg/1mL
Injection, solutionIntravenous80 mg/4mL
Injection, solution, concentrateIntravenous160 mg/8mL
Injection, solution, concentrateIntravenous20 mg/2mL
Injection, solution, concentrateIntravenous20 mg/1mL
Injection, solution, concentrateIntravenous200 mg/20mL
Injection, solution, concentrateIntravenous80 mg/8mL
Injection; injection, solution, concentrateIntravenous40 mg/mL
KitIntravenous40 mg/1mL
SolutionIntravenous20 mg/1mL
SolutionIntravenous21.340 mg
Solution, concentrateIntravenous120 mg
Solution, concentrateIntravenous160 mg
Solution, concentrateIntravenous20 mg
Solution, concentrateIntravenous80 mg
Solution, concentrateIntravenous8000000 mg
Injection, solution, concentrateIntravenous; Parenteral160 MG/8ML
Injection, solution, concentrateIntravenous; Parenteral20 MG/1ML
Injection, solution, concentrateIntravenous; Parenteral80 MG/4ML
SolutionIntravenous20 mg/ml
Injection, solutionIntravenous160 mg/16mL
Injection, solutionIntravenous20 mg/2mL
Injection, solutionIntravenous80 mg/8mL
SolutionIntravenous10 mg / mL
SolutionIntravenous20 mg / 0.72 mL
SolutionIntravenous20 mg / mL
SolutionIntravenous80 mg / 2.88 mL
Injection, solution, concentrateIntravenous180 MG/9ML
InjectionParenteral20 mg/ml
Injection, solution, concentrateIntravenous200 mg/10ml
InjectionIntravenous20 mg/1mL
Injection, solution, concentrateIntravenous; Parenteral10 MG/ML
Injection, powder, lyophilized, for solutionParenteral80 mg
Injection, solution, concentrateIntravenous10 mg/ml
Injection, powder, lyophilized, for solutionParenteral20 mg
Injection, solution, concentrateIntravenous20 mg/ml
Injection, solution, concentrateIntravenous20 mg/0.72ml
Injection, solution, concentrateIntravenous80 mg/2.88ml
SolutionIntravenous160 mg
SolutionIntravenous40 mg
Injection, solution, concentrate160 mg/8ml
Injection, powder, lyophilized, for solutionIntravenous20 mg
Injection, powder, lyophilized, for solutionIntravenous80 mg
SolutionIntravenous20 mg/0.5ml
SolutionIntravenous80 mg/2ml
InjectionIntravenous20 mg/0.5ml
InjectionIntravenous80 mg/2ml
Injection, solution, concentrateIntravenous
Injection, solution, concentrateIntravenous160 mg
Injection, solution, concentrateIntravenous20 mg
Injection, solution, concentrateIntravenous40 mg
Injection, solution, concentrateIntravenous40 mg/2ml
Injection, solution, concentrate
SolutionIntravenous160 mg/16ml
SolutionIntravenous20 mg/2ml
SolutionIntravenous80 mg/8mL
Injection, solution, concentrateIntravenous10 mg/1ml
SolutionIntravenous20.00 mg
SolutionIntravenous20.0000 mg
Injection, powder, for solutionIntravenous20 mg
SolutionParenteral80 mg
InjectionIntravenous
Solution40 mg/1ml
SolutionIntravenous80 mg
Solution, concentrateIntravenous40.0 mg/ml
SolutionIntravenous20 mg
Kit; solutionIntravenous20 mg / 0.5 mL
Kit; solutionIntravenous80 mg / 2 mL
Injection, solution, concentrateIntravenous160 mg/16ml
SolutionIntravenous160 mg / 8 mL
SolutionIntravenous80 mg / 4 mL
SolutionIntravenous20.000 mg/ml
Injection, solution, concentrateIntravenous; Parenteral20 MG/ML
Injection, solution, concentrateIntravenous120 MG/6ML
Injection, solution, concentrateIntravenous140 MG/7ML
SolutionIntravenous10 mg
Injection, solution, concentrateIntravenous20 mg/0.5ml
Injection, solution, concentrateIntravenous40 mg/1mL
Injection, solution, concentrateIntravenous80 MG
Injection, solution, concentrateIntravenous80 mg/2ml
Injection, solution, concentrateIntravenous80 mg/4mL
Injection, solution, concentrateIntravenous; Parenteral20 MG
SolutionIntravenous20 mg / 0.5 mL
SolutionIntravenous80 mg / 2 mL
InjectionIntravenous20 mg
Injection, solutionIntravenous
InjectionIntravenous80 mg
SolutionIntravenous80 mg/4ml
Solution
SolutionParenteral20.000 mg
Injection, solutionIntravenous40 mg/1ml
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)Region
US5438072No1995-08-012014-05-22US flag
US4814470No1989-03-212010-05-14US flag
CA2150576No2005-06-212013-11-26Canada flag
CA2149055No2003-01-072013-11-08Canada flag
US8940786No2015-01-272033-09-30US flag
US9308195No2016-04-122033-09-30US flag
US9763880No2017-09-192033-09-30US flag
US10842770No2020-11-242031-08-04US flag
US10398785No2019-09-032036-03-14US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)232 °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)11.9Chemaxon
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
Polarizability82.15 Å3Chemaxon
Number of Rings6Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-0340122910-e12b738cbd3456297ad3
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-05fu-6920236210-707f46ab19523c2b7ea0
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0563-1340316920-7f0a86f0db21c350ff90
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a6u-5970012010-344a4d6d57edff815836
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-1900001010-965aeebb2bce771bba25
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00c0-9810002020-267edc7870efe84d94c4
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-05ru-0190242610-65adb22f0ea48e428655
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-05fu-5690415110-7ea9ce4759ec219730ac
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-057l-1580214930-333636db3b7509eb703b
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0aec-6960305010-ff09ac97cf9adb703af0
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a6r-3910006120-d59b1343df2d017c76db
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-056r-9700002120-add8df16e3c052efc6aa
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-272.1359646
predicted
DarkChem Lite v0.1.0
[M-H]-284.5782646
predicted
DarkChem Lite v0.1.0
[M-H]-259.6681
predicted
DeepCCS 1.0 (2019)
[M-H]-272.1359646
predicted
DarkChem Lite v0.1.0
[M-H]-284.5782646
predicted
DarkChem Lite v0.1.0
[M-H]-259.6681
predicted
DeepCCS 1.0 (2019)
[M+H]+268.2214646
predicted
DarkChem Lite v0.1.0
[M+H]+284.5180646
predicted
DarkChem Lite v0.1.0
[M+H]+261.53506
predicted
DeepCCS 1.0 (2019)
[M+H]+268.2214646
predicted
DarkChem Lite v0.1.0
[M+H]+284.5180646
predicted
DarkChem Lite v0.1.0
[M+H]+261.53506
predicted
DeepCCS 1.0 (2019)
[M+Na]+268.5515646
predicted
DarkChem Lite v0.1.0
[M+Na]+282.6669646
predicted
DarkChem Lite v0.1.0
[M+Na]+267.50125
predicted
DeepCCS 1.0 (2019)
[M+Na]+268.5515646
predicted
DarkChem Lite v0.1.0
[M+Na]+282.6669646
predicted
DarkChem Lite v0.1.0
[M+Na]+267.50125
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
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
Uniprot Name
Tubulin beta-1 chain
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. [Article]
  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. [Article]
  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. [Article]
  4. Belani CP, Eckardt J: Development of docetaxel in advanced non-small-cell lung cancer. Lung Cancer. 2004 Dec;46 Suppl 2:S3-11. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
Microtubule-associated protein 2
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
General Function
Structural molecule activity
Specific Function
Non-neuronal microtubule-associated protein. Promotes microtubule assembly.
Gene Name
MAP4
Uniprot ID
P27816
Uniprot Name
Microtubule-associated protein 4
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. [Article]
Kind
Protein
Organism
Humans
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 neu...
Gene Name
MAPT
Uniprot ID
P10636
Uniprot Name
Microtubule-associated protein tau
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. [Article]
Kind
Protein
Organism
Humans
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. Appea...
Gene Name
BCL2
Uniprot ID
P10415
Uniprot Name
Apoptosis regulator Bcl-2
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. [Article]
  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. [Article]
  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. [Article]
  4. Petrylak DP: Chemotherapy for androgen-independent prostate cancer. World J Urol. 2005 Feb;23(1):10-3. Epub 2005 Feb 1. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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 an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
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. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Baumhakel M, Kasel D, Rao-Schymanski RA, Bocker R, Beckurts KT, Zaigler M, Barthold D, Fuhr U: Screening for inhibitory effects of antineoplastic agents on CYP3A4 in human liver microsomes. Int J Clin Pharmacol Ther. 2001 Dec;39(12):517-28. [Article]
  2. Clarke SJ, Rivory LP: Clinical pharmacokinetics of docetaxel. Clin Pharmacokinet. 1999 Feb;36(2):99-114. doi: 10.2165/00003088-199936020-00002. [Article]
  3. Hirth J, Watkins PB, Strawderman M, Schott A, Bruno R, Baker LH: The effect of an individual's cytochrome CYP3A4 activity on docetaxel clearance. Clin Cancer Res. 2000 Apr;6(4):1255-8. [Article]
  4. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
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 un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
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 un...
Gene Name
CYP1B1
Uniprot ID
Q16678
Uniprot Name
Cytochrome P450 1B1
Molecular Weight
60845.33 Da
References
  1. Bournique B, Lemarie A: Docetaxel (Taxotere) is not metabolized by recombinant human CYP1B1 in vitro, but acts as an effector of this isozyme. Drug Metab Dispos. 2002 Nov;30(11):1149-52. doi: 10.1124/dmd.30.11.1149. [Article]

Transporters

Kind
Protein
Organism
Humans
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
Uniprot Name
Multidrug resistance protein 1
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
Multidrug resistance-associated protein 7
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. [Article]
Kind
Protein
Organism
Humans
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), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
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. [Article]
Kind
Protein
Organism
Humans
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 sulf...
Gene Name
SLC22A7
Uniprot ID
Q9Y694
Uniprot Name
Solute carrier family 22 member 7
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. [Article]
Kind
Protein
Organism
Humans
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 fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
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. [Article]
  2. Nakanishi T, Ross DD: Breast cancer resistance protein (BCRP/ABCG2): its role in multidrug resistance and regulation of its gene expression. Chin J Cancer. 2012 Feb;31(2):73-99. doi: 10.5732/cjc.011.10320. Epub 2011 Nov 18. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
Canalicular multispecific organic anion transporter 1
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. [Article]
Kind
Protein
Organism
Humans
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, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
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. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48