Drug nameDocetaxel
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 1 mole docetaxel per mole tubulin in microtubules.
DrugBankPrimary Accession Number: DB01248
DIN02177080
TypeApproved, Investigational, Small Molecule
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. Lastly, for use, in combination with prednisone, in the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer.
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 -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.
AbsorptionNot available
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.
Protein BindingAbout 94% protein bound, mainly to a1-acid glycoprotein, albumin, and lipoproteins.
Interactions
RXListhttp://www.rxlist.com/cgi/generic3/docetaxel.htm
KEGGdrug: Not available / compound: C11231
PubChemcompound: 148124 / substance: 13410
PharmGKBPA449383
Metabolizing Enzymes
NameGeneEntrezIDUniprotSNP
Thymidine phosphorylaseECGF11890P19971
Target
NameGeneEntrezIDSwissprotSNP
Apoptosis regulator Bcl-2BCL2596BCL2_HUMANrs1801018 rs1800477
Tubulin beta-1 chainTUBB181027TBB1_HUMANrs35565630 rs35989782 rs6070697 rs163777 rs45599044 rs41303899 rs35505670 rs34793043 rs34074666 rs6128481 rs463312 rs415064
FilesDB01248.mol | DB01248_1999-12-01.pdf | DB01248_71.pdf | pdb_2002842824834-0.pdb | sdf_4428484514996-0.sdf |
Smilesisomeric:
CC(=O)O[C@@]12CO[C@@H]1C[C@H](O)[C@]1(C)[C@@H]2[C@H](OC(=O)C2=CC=CC=C2
)[C@]2(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C3=CC=CC=C3)C(C)=
C([C@@H](O)C1=O)C2(C)C
canonical:
CC(=O)OC12COC1CC(O)C1(C)C2C(OC(=O)C2=CC=CC=C2)C2(O)CC(OC(=O)C(O)C(NC(=
O)OC(C)(C)C)C3=CC=CC=C3)C(C)=C(C(O)C1=O)C2(C)C

© 2010-2020 All rights reserved. King Abdullah University of Science and Technology, All rights reserved