ChemFOnt: Showing chemical card for Docetaxel (CFc000009654)

Record Information

Version

1.0

Creation Date

2022-08-28 10:25:12 UTC

Update Date

2022-09-13 18:56:51 UTC

Chemfont ID

CFc000009654

Molecule Identification

Common Name

Docetaxel

Definition

Docetaxel (sold under the brand name Taxotere) is a clinically well-established anti-mitotic chemotherapy medication (that is, it interferes with cell division). It is used mainly for the treatment of breast, ovarian, prostate, 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. Docetaxel has been FDA-approved to treat 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. Docetaxel has a European approval for use in hormone-refractory prostate cancer. Docetaxel is a chemotherapeutic agent and is a cytotoxic compound. It is effectively a biologically damaging drug. As with all chemotherapy, adverse effects are common and many varying side-effects have been documented. Because docetaxel is a cell-cycle specific agent, it is cytotoxic to all dividing cells in the body. This includes tumour cells as well as hair follicles, bone marrow, and other germ cells. For this reason, common chemotherapy side effects such as alopecia occur (this can sometimes be permanent). The drug company Sanofi Aventis claims that they do not routinely keep this data. A survey being conducted in northwest France aims to establish exactly how many patients are being disfigured in this way. Independent studies show it could be as high as 6.3% which puts this ASE in the 'common and frequent' classification. Docetaxel is mainly metabolized in the liver by the cytochrome P450 CYP3A4 and CYP3A5 subfamilies of isoenzymes. Metabolism is principally oxidative and at the tert-butylpropionate side chain, resulting first in an alcohol docetaxel (M2), which is then cyclized to three further metabolites (M1, M3, and M4). M1 and M3 are two diastereomeric hydroxyoxazolidinones and M4 is an oxazolidinedione. Phase II trials of 577 patients showed that docetaxel clearance is related to body surface area and plasma levels of hepatic enzyme alpha-1-acid glycoprotein. Docetaxel is of the chemotherapy drug class taxane and is a semi-synthetic analogue of paclitaxel (Taxol), an extract from the bark of the rare Pacific yew tree Taxus brevifolia. Due to the scarcity of paclitaxel, extensive research was carried out which lead to the formulation of docetaxel, an esterified product of 10-deacetylbaccatin III. It was extracted from the renewable and readily available European yew tree. Drug interactions may be the result of altered pharmacokinetics or pharmacodynamics due to one of the drugs involved. Cisplatin, dexamethasone, doxorubicin, etoposide, and vinblastine are all potentially co-administered with docetaxel and did not modify docetaxel plasma binding in phase II studies. Cisplatin is known to have a complex interaction with some CYPs and has, in some events, been shown to reduce docetaxel clearance by up to 25%. Anticonvulsants induce some metabolic pathways relevant to docetaxel. CYP450 and CYP3A show increased expression in response to the use of anticonvulsants and the metabolism of docetaxel metabolite M4 is processed by these CYPs. A corresponding increase in clearance of M4 by 25% is observed in patients taking phenytoin and phenobarbital, common anticonvulsants. STAMPEDE is a UK-based six-arm, five-stage, open-label randomized controlled trial involving more than 3000 men. Arms C and E of this trial involve administering docetaxel to men starting long-term hormone therapy for the first time. This could be newly diagnosed metastatic, non-metastatic, or high-risk, previously-treated prostate cancer. The trial tests the value of the drug earlier in the treatment pathway instead of waiting until it has become androgen-independent.

Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetylpaclitaxel	ChEBI
N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol	ChEBI
TXL	ChEBI
Taxotere	Kegg
Docetaxel anhydrous	HMDB
Docetaxel, trihydrate	HMDB
Docetaxel trihydrate	HMDB
Docetaxol	HMDB
N-Debenzoyl-N-tert-butoxycarbonyl-10-deacetyltaxol	HMDB
Taxoltere metro	HMDB
Docetaxel hydrate	HMDB
N Debenzoyl N tert butoxycarbonyl 10 deacetyltaxol	HMDB

Chemical Formula

C₄₃H₅₃NO₁₄

Average Molecular Weight

807.8792

Monoisotopic Molecular Weight

807.346605409

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

Traditional Name

(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetyloxy)-15-{[(2R,3S)-3-[(tert-butoxycarbonyl)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

CAS Registry Number

114977-28-5

SMILES

[H][C@@]12C[C@H](O)[C@@]3(C)C(=O)[C@H](O)C4=C(C)[C@H](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)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C1=CC=CC=C1

InChI Identifier

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

InChI Key

ZDZOTLJHXYCWBA-VCVYQWHSSA-N

Chemical Taxonomy

Description

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

Substituents

Taxane diterpenoid
Benzoate ester
Benzoic acid or derivatives
Tricarboxylic acid or derivatives
Benzoyl
Fatty acid ester
Monocyclic benzene moiety
Fatty acyl
Monosaccharide
Benzenoid
Cyclic alcohol
Carbamic acid ester
Tertiary alcohol
Carboxylic acid ester
Ketone
Carbonic acid derivative
Oxetane
Secondary alcohol
Organoheterocyclic compound
Oxacycle
Ether
Dialkyl ether
Carboxylic acid derivative
Polyol
Organic nitrogen compound
Hydrocarbon derivative
Alcohol
Carbonyl group
Organic oxide
Organonitrogen compound
Organooxygen compound
Organic oxygen compound
Organopnictogen compound
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

tetracyclic diterpenoid (CHEBI:4672 )

Functional Ontology

Physiological effect

Not Available

Disposition

Biological location

Non-excretory biofluid

Biofluid or Excreta

Blood (PMID: 21059682)

Organ

Liver (HMDB: HMDB0015378)
Kidney (HMDB: HMDB0015378)

Excreta

Biofluid or Excreta

Urine (PMID: 21059682)

Cellular substructure

Source

Exogenous

Exogenous (HMDB: HMDB0015378)

Endogenous

Endogenous (HMDB: HMDB0015378)

Process

Naturally occurring process

Biological process

Biochemical pathway

Drug action pathway

Docetaxel Pathway (HMDB: HMDB0015378)
Docetaxel Action Pathway (PathBank: SMP0000435)

Role

Industrial application

Antineoplastic agent (HMDB: HMDB0015378)

Manufacturing industry

Material processing agent

Coloring agent

Fluorescent agent

Photosensitizing agent (HMDB: HMDB0015378)

Pharmaceutical industry

Antimicrobial agent

Antimalarial (HMDB: HMDB0015378)

Physical Properties

Predicted Properties

Property	Value	Source
Water Solubility	0.013 g/L	ALOGPS
logP	2.59	ALOGPS
logP	2.92	ChemAxon
logS	-4.8	ALOGPS
pKa (Strongest Acidic)	10.96	ChemAxon
pKa (Strongest Basic)	-3	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	10	ChemAxon
Hydrogen Donor Count	5	ChemAxon
Polar Surface Area	224.45 Å²	ChemAxon
Rotatable Bond Count	13	ChemAxon
Refractivity	203.9 m³·mol⁻¹	ChemAxon
Polarizability	82.15 Å³	ChemAxon
Number of Rings	6	ChemAxon
Bioavailability	No	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon