Docetaxel

Title: Docetaxel
CAS Registry Number: 114977-28-5
CAS Name: (aR,bS)-b-[[(1,1-Dimethylethoxy)carbonyl]amino]-a-hydroxybenzenepropanoic acid (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,6,11-trihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl ester
Additional Names: N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol
Manufacturers' Codes: NSC-628503; RP-56976
Trademarks: Taxotere (Aventis)
Molecular Formula: C43H53NO14
Molecular Weight: 807.88
Percent Composition: C 63.93%, H 6.61%, N 1.73%, O 27.73%
Literature References: Semisynthetic derivative of paclitaxel, q.v., prepd using a natural precursor, 10-deacetylbaccatin III, extracted from the needles of the European yew tree, Taxus baccata L., Taxaceae. Antimitotic agent that promotes the assembly of microtubules and inhibits their depolymerization to free tubulin. Prepn: M. Colin et al., EP 253738; eidem, US 4814470 (1988, 1989 both to Rhône-Poulenc Sante); L. Mangatal et al., Tetrahedron 45, 4177 (1989). Synthesis of the side chain: J.-N. Denis et al., J. Org. Chem. 56, 6939 (1991). Structure-activity study: F. Guéritte-Voegelein et al., J. Med. Chem. 34, 992 (1991). Cytotoxic activity and mechanism of action: I. Ringel, S. B. Horwitz, J. Natl. Cancer Inst. 83, 288 (1991). In vivo antitumor activity: M.-C. Bissery et al., Cancer Res. 51, 4845 (1991). HPLC determn: J. C. Vergniol et al., J. Chromatogr. 582, 273 (1992). Clinical pharmacokinetics and toxicology: J.-M. Extra et al., Cancer Res. 53, 1037 (1993). Clinical trials in prostate cancer: I. F. Tannock et al., N. Engl. J. Med. 351, 1502 (2004); D. P. Petrylak et al., ibid. 1513. Symposium on clinical experience: Semin. Oncol. 27, Suppl. 3, 1-29 (2000). Review of mechanism of action and combination therapies: R. S. Herbst, F. R. Khuri, Cancer Treat. Rev. 29, 407-415 (2003); of clinical studies in non-small cell lung cancer: A. M. Davies et al., Expert Opin. Pharmacother. 4, 553-565 (2003).
Properties: mp 232°. [a]D -36° (c = 0.74 in ethanol). uv max: 230, 275, 283 nm (e 14800, 1730, 1670).
Melting point: mp 232°
Optical Rotation: [a]D -36° (c = 0.74 in ethanol)
Absorption maximum: uv max: 230, 275, 283 nm (e 14800, 1730, 1670)
Therap-Cat: Antineoplastic.
Keywords: Antineoplastic; Alkaloids/Natural Products; Taxanes.
Docosahexaenoic Acid Docusate Calcium Docusate Sodium Dodecahedrane Dodecamethylcyclohexasiloxane

Docetaxel
Docetaxel.svg
Docetaxel3D.png
Systematic (IUPAC) name
1,7β,10β-trihydroxy-9-oxo-5β,20-epoxytax-11-ene-2α,4,13α-triyl 4-acetate 2-benzoate 13-{(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoate}
Clinical data
Trade names Taxotere
AHFS/Drugs.com monograph
MedlinePlus a696031
Pregnancy cat. D (US)
Legal status Prescription only
Routes IV
Pharmacokinetic data
Bioavailability NA
Protein binding >98%
Metabolism Hepatic
Half-life 86 hours
Excretion Biliary
Identifiers
CAS number 114977-28-5 N
ATC code L01CD02
PubChem CID 148124
DrugBank DB01248
ChemSpider 130581 N
UNII 699121PHCA N
KEGG D07866 N
ChEBI CHEBI:4672 N
ChEMBL CHEMBL92 N
Chemical data
Formula C43H53NO14 
Mol. mass 807.879 g/mol
 N (what is this?)  (verify)

Docetaxel (as generic or under the trade name Taxotere) is a clinically well-established anti-mitotic chemotherapy medication (medication which interferes with cell division). It is used mainly for the treatment of breast, ovarian, prostate, and non-small cell lung cancer.[1][2][3] Docetaxel has an FDA approved claim for treatment of patients who have locally advanced, or metastatic breast or non small-cell lung cancer who have undergone anthracycline-based chemotherapy and failed to stop cancer progression or relapsed[4] and a European approval for use in hormone-refractory prostate cancer.[5]

According to a 2005 article in the journal Drugs, docetaxel administered as a one-hour infusion every three weeks generally over a ten cycle course, docetaxel is considered as or more effective than doxorubicin, paclitaxel and fluorouracil as a cytotoxic agent.[1] However the effectiveness of docetaxel versus paclitaxel and other taxanes is still controversial. Several more recent articles have found "no evidence that regimens containing docetaxel yield greater benefits than those including paclitaxel."[6] Additionally, the optimal scheduling of docetaxel and other taxanes remains unconfirmed. A three-week administration schedule used to be and is still considered effective but new studies are indicating a weekly schedule might be better. A 2010 article in Current Clinical Pharmacology states, "weekly administration has emerged as the optimal schedule." Docetaxel is marketed worldwide under the name Taxotere by Sanofi-Aventis.[7] Annual sales in 2010 were Euro 2.122 billion ($US 3.1 billion). The patent expired in 2010.[citation needed]

Clinicians sometimes use the abbreviation "TXT" for docetaxel, although (like many medical abbreviations) it is not a unique identifier.