Docetaxel

Structural formula
General
Non-proprietary name	Docetaxel
other names	(2 R , 3 S ) -4-acetoxy-2 α -benzyloxy-13- [3- ( N - tert -butoxycarbonyl) amino-2-hydroxy-3-phenyl] propionyl-5 β , 20-epoxy-1, 7 β , 10 β -trihydroxy-9-oxotax-11-en-13 α -yl ester ( IUPAC ) ; (2 R , 3 S ) - N - ( tert -Butoxycarbonyl) -2-hydroxy-3-phenyl-β-alanine- (4-acetoxy-2 α -benzoyloxy-5 β , 20-epoxy-1,7 β , 10 β- trihydroxy-9-oxo-11-taxen-13 α -yl ester);
Molecular formula	C 43 H 53 NO 14
Brief description	white solid
External identifiers / databases
EC number	601-339-2
ECHA InfoCard	100.129.246
PubChem	148124
DrugBank	DB01248
Wikidata	Q420436
Drug information
ATC code	L01 CD02
Drug class	Cytostatic
Mechanism of action	Microtubule Lock
properties
Molar mass	807.88 g mol −1
Physical state	firmly
Melting point	232 ° C
solubility	almost insoluble in water
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances	no GHS pictograms
	no GHS pictograms
H and P phrases	H: no H-phrases
	P: no P-phrases
Toxicological data	156 mg kg −1 ( LD 50 , mouse , iv )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Docetaxel (trade name Taxotere ^® , manufacturer: Sanofi-Aventis ) is a cytostatic from the group of taxanes . Docetaxel is structurally a descendant of paclitaxel and is produced semi-synthetically from precursors found in the European yew tree .

synthesis

The first taxane paclitaxel ( Taxol ) was isolated from the bark of the Pacific yew tree ( Taxus brevifolia ). However, since this tree species is one of the slowest growing trees in the world, efforts have been made to obtain raw materials for taxane synthesis from other plants. It was possible to isolate the substance 10-deacetyl-baccatin III (10-DAB-III) from the European yew tree ( Taxus baccata ), which is available in much larger quantities , and after esterification results in the semi-synthetic taxane docetaxel.

effect

The cytostatic effect of docetaxel is based on its binding to the microtubule device. This stabilizes the microtubules and blocks mitosis of the cell. Docetaxel is hepatic metabolism (via the liver metabolizes).

application areas

Docetaxel is used in the treatment of breast cancer (breast cancer), non-small cell lung cancer (lung cancer), prostate cancer , ovarian cancer (ovarian cancer), stomach cancer and head and neck cancer .

Side effects

The main side effects are neuropathy , blood formation disorders ( neutropenia , anemia , thrombocytopenia ) and liver dysfunction. After the European Medicines Agency (EMA) received increased reports of neutropenic enterocolitis under treatment with docetaxel, the Pharmacovigilance Committee reassessed the safety of the drug. This side effect, which results in a serious inflammatory reaction in the intestine, is already classified as “rare” in the product information and instructions for use, which means that it occurs in less than 1 in 1000 patients treated. In conclusion, the committee came to the conclusion that there will be no reclassification.

Web links

Taxotere (US website of the manufacturer Sanofi-Aventis)
Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for: Docetaxel

literature

Aktories, Förstermann, Hofmann, Starke: General and Special Pharmacology and Toxicology Review , Elsevier Urban & Fischer, 2009

Individual evidence

↑ ^a ^b ^c ^d Datasheet Docetaxel from Sigma-Aldrich , accessed on May 13, 2017 ( PDF ).
↑ ^a ^b Entry on docetaxel in the ChemIDplus database of the United States National Library of Medicine (NLM) .
↑ PRAC concludes there is no evidence of a change in known risk of neutropenic enterocolitis with docetaxel , PM EMA dated June 6, 2017, accessed on July 5, 2017.

[sigma-1] Datasheet Docetaxel from Sigma-Aldrich , accessed on May 13, 2017 ( PDF ).

[ChemIDplus-2] Entry on docetaxel in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[3] PRAC concludes there is no evidence of a change in known risk of neutropenic enterocolitis with docetaxel , PM EMA dated June 6, 2017, accessed on July 5, 2017.