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Details

Stereochemistry ACHIRAL
Molecular Formula C6H12N3PS
Molecular Weight 189.218
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of THIOTEPA

SMILES

S=P(N1CC1)(N2CC2)N3CC3

InChI

InChIKey=FOCVUCIESVLUNU-UHFFFAOYSA-N
InChI=1S/C6H12N3PS/c11-10(7-1-2-7,8-3-4-8)9-5-6-9/h1-6H2

HIDE SMILES / InChI

Molecular Formula C6H12N3PS
Molecular Weight 189.218
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

N,N’N’-triethylenethiophosphoramide (ThioTEPA) is a cancer chemotherapeutic member of the alkylating agent group, now in use for over 50 years. It is a stable derivative of N,N’,N’’- triethylenephosphoramide (TEPA). The radiomimetic action of thiotepa is believed to occur through the release of ethylenimine radicals which, like irradiation, disrupt the bonds of DNA. One of the principal bond disruptions is initiated by alkylation of guanine at the N-7 position, which severs the linkage between the purine base and the sugar and liberates alkylated guanines. Thiotepa has been used in the palliation of a wide variety of neoplastic diseases. The more consistent results have been seen in: adenocarcinoma of the breast, adenocarcinoma of the ovary, superficial papillary carcinoma of the urinary bladder and for controlling intracavitary effusions secondary to diffuse or localized neoplastic diseases of various serosal cavities.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
THIOTEPA
Primary
THIOTEPA
Primary
THIOTEPA

Cmax

ValueDoseCo-administeredAnalytePopulation
1828 ng/mL
80 mg 1 times / 4 weeks multiple, intravenous
THIOTEPA serum
Homo sapiens
1331 ng/mL
60 mg 1 times / 4 weeks multiple, intravenous
THIOTEPA serum
Homo sapiens
0.098 μg/mL
60 mg single, intravesical
THIOTEPA urine
Homo sapiens
0.129 μg/mL
60 mg single, intravesical
THIOTEPA urine
Homo sapiens
8.91 μg/mL
200 mg/m² single, intravenous
THIOTEPA plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
4127 ng × h/mL
80 mg 1 times / 4 weeks multiple, intravenous
THIOTEPA serum
Homo sapiens
2832 ng × h/mL
60 mg 1 times / 4 weeks multiple, intravenous
THIOTEPA serum
Homo sapiens
22.4 μg × min/mL
60 mg single, intravesical
THIOTEPA urine
Homo sapiens
24.8 μg × min/mL
60 mg single, intravesical
THIOTEPA urine
Homo sapiens
28.24 μg × h/mL
200 mg/m² single, intravenous
THIOTEPA plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
2.3 h
80 mg 1 times / 4 weeks multiple, intravenous
THIOTEPA serum
Homo sapiens
2.4 h
60 mg 1 times / 4 weeks multiple, intravenous
THIOTEPA serum
Homo sapiens
91 min
60 mg single, intravesical
THIOTEPA urine
Homo sapiens
89 min
60 mg single, intravesical
THIOTEPA urine
Homo sapiens
2.55 h
20 mg/m² single, intravenous
THIOTEPA plasma
Homo sapiens
4.15 h
200 mg/m² single, intravenous
THIOTEPA plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
85%
20 mg/m² single, intravenous
THIOTEPA plasma
Homo sapiens

Doses

AEs

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
Thiotepa may be given by rapid intravenous administration in doses of 0.3 to 0.4 ug/kg. Doses should be given at 1 to 4 week intervals.
Route of Administration: Intravenous
In Vitro Use Guide
The cytotoxicity of thiotepa toward MCF-7 cells was markedly dependent on the presence of oxygen during the period of drug exposure, with a 3-log greater cell kill at 500 umol with cells that were normally oxygenated compared with hypoxic cells.
Substance Class Chemical
Record UNII
905Z5W3GKH
Record Status Validated (UNII)
Record Version