Page last updated: 2024-12-05

triethylenephosphoramide

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Triethylenephosphoramide (TEPA) is a nitrogen mustard alkylating agent that was previously used as a chemotherapy drug. It works by interfering with DNA replication and cell division. TEPA has been largely replaced by other, more effective and less toxic chemotherapeutic agents. It was primarily studied for its effects on cancer cells and its potential use in treating various cancers, including lymphoma, leukemia, and ovarian cancer. However, due to its severe side effects, including bone marrow suppression and nausea, its use has been discontinued in most clinical settings. Research into TEPA's mechanisms of action and its potential applications in other fields, such as the development of new chemotherapy drugs, is ongoing.'

Triethylenephosphoramide: An insect chemosterilant and an antineoplastic agent. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID11016
CHEMBL ID670
CHEBI ID82546
SCHEMBL ID11572
MeSH IDM0021170

Synonyms (94)

Synonym
triethylenfosforamid
4-20-00-00048 (beilstein handbook reference)
gl19m2ke52 ,
phosphoramide, n,n',n''-triethylene-
n,n',n''-triethylenephosphoramide
tris-(1-aziridinyl)fosfinoxid
unii-gl19m2ke52
phosphoric triamide, n,n',n''-triethylene-
1,1',1''-phosphinylidynetrisaziridine
phosphoric triamide, n,n',n''-tri-1,2-ethanediyl-
ai3-24915
triethylenfosforamid [czech]
tepa (van)
einecs 208-892-5
n,n',n''-tri-1,2-ethanediylphosphoric triamide
triaethylenphosphorsaeureamid [german]
nsc 9717
hsdb 1011
un2501
tris-(1-aziridinyl)fosfinoxid [czech]
tris-(1-aziridinyl)-phosphineoxide
n,n',n''-triethylenephosphoric triamide
aziridine, 1,1',1''-phosphinylidynetris-
triethylenepyrophosphoramide
tri(aziridin-1-yl)phosphine oxide
brn 0145971
phosphoric acid triethylene imide
triaethylenphosphorsaeureamid
tri(aziridinyl)phosphine oxide
ent 24,915
TEF ,
imperon fixer t
aziridine,1',1''-phosphinylidynetris-
1,1''-phosphinylidynetrisaziridine
cbc 906288
triethylene phophoramide
tri(1-aziridinyl)phosphine oxide
phosphoric acid triethyleneimine
triethylenephosphoramide
wln: t3ntj apo&- at3ntj&- at3ntj
ent 24915
aphoxide
tepa
triethylenephosphorotriamide
545-55-1
phosphoric triamide,n',n -triethylene-
tris(1-aziridine)phosphine oxide
triaziridinophosphine oxide
n,n''-triethylenephosphoric triamide
a 6366
hexamethylphosphoric triamide tris(1-aziridinyl)phosphine oxide
n,n -triethylenephosphoramide
tapo
tris(aziridinyl)phosphine oxide
sk 3818
tris(1-aziridinyl)phosphine oxide
tri-1-aziridinylphosphine oxide
triaziridinylphosphine oxide
triethylene phosphoramide
phosphoric triamide,n',n''-tri-1,2-ethanediyl-
n,n''-triethylenephosphoramide
phosphine oxide, tris(1-aziridinyl)-
triethylenephosphoric triamide
n,n''-tri-1,2-ethanediylphosphoric triamide
nsc-9717
phosphoramide,n',n -triethylene-
sk-3818
tris-(1-aziridinyl)phosphine oxide
phosphoric triamide,n',n''-triethylene-
tris(n-ethylene)phosphorotriamidate
nsc9717
phosphoramide,n',n''-triethylene-
nsc221657
nsc-221657
27030-72-4
CHEMBL670 ,
chebi:82546 ,
tepa (possesses cytotoxic activity)
1-[bis(aziridin-1-yl)phosphoryl]aziridine
FT-0658217
tpea
bdbm50067462
1-(diaziridin-1-ylphosphoryl)aziridine
n,n:n'',n'':n'''',n''''-tri-1,2-ethanediylphosphorictriamide(tepa)
AKOS006281396
C19543
A830239
1-[bis(1-aziridinyl)phosphoryl]aziridine
triethylenephosphoramide [mi]
1,1',1''-phosphinylidynetris(aziridine)
tepa [hsdb]
SCHEMBL11572
DTXSID4052716
1,1',1''-phosphoryltriaziridine

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" The LD50 of 5 is 270 mg/kg, while that of Thio-TEPA is 18 mg/kg."( In the search for new anticancer drugs. X. N,N; N',N'-bis(1,2-ethanediyl)-N''-(1-oxyl-2,2,6,6-tetramethyl- 4-piperidinylaminocarbonyl) phosphoric triamide--a new potential anticancer drug of high activity and low toxicity.
Li, SW; Sosnovsky, G, 1985
)
0.27
" No adverse events were registered."( Therapeutic education and physical activity are feasible and safe in hematologic cancer patients referred to chemotherapy: results of a randomized controlled trial.
Accogli, MA; Costi, S; Denti, M; Fugazzaro, S, 2022
)
0.72
"Multidimensional rehabilitation interventions are feasible and safe in this population, and larger trials should focus on the efficacy of such approaches on clinically relevant outcomes."( Therapeutic education and physical activity are feasible and safe in hematologic cancer patients referred to chemotherapy: results of a randomized controlled trial.
Accogli, MA; Costi, S; Denti, M; Fugazzaro, S, 2022
)
0.72

Pharmacokinetics

ExcerptReferenceRelevance
"A pharmacokinetic study of randomised crossover design was carried out in which eight patients with recurrent stage pTa or pT1 transitional cell carcinoma of the bladder were given thioTEPA (30 mg) in distilled water or in 10% (v/v) Tween 80 (30 ml) intravesically for 2 h, followed 3 months later by the alternative treatment."( ThioTEPA pharmacokinetics during intravesical chemotherapy and the influence of Tween 80.
Bibby, MC; Fenwick, E; Jenkins, WE; Loadman, PM; Masters, JR; McDermott, BJ; Mundy, AR; Shah, PJ, 1990
)
0.28
" Linear regression analyses of pharmacokinetic parameters versus myelosuppression revealed statistically significant correlations between thio-TEPA pharmacokinetics and the percentage of reductions in leukocytes and platelets at their mean nadirs."( Pharmacokinetics of thio-TEPA and TEPA in the conventional dose-range and its correlation to myelosuppressive effects.
Hagen, B, 1991
)
0.28
" The half-life of thioTEPA ranged from 51."( Phase I/pharmacokinetic reevaluation of thioTEPA.
Cole, D; DeLap, RJ; DeVito, J; Engstrom, PF; LaCreta, F; Litwin, S; O'Dwyer, PJ; Peter, R; Poplack, D; Tartaglia, L, 1991
)
0.28
" The aim of this study was to develop a population pharmacokinetic model describing the complex pharmacokinetics of CP, 4OHCP, 2DCECP, and PM when CP is administered in a high-dose combination with thiotepa and carboplatin."( Population pharmacokinetics of cyclophosphamide and its metabolites 4-hydroxycyclophosphamide, 2-dechloroethylcyclophosphamide, and phosphoramide mustard in a high-dose combination with Thiotepa and Carboplatin.
Beijnen, JH; de Jonge, ME; Huitema, AD; Rodenhuis, S; van Dam, SM, 2005
)
0.33
" Relations between allelic variants and elimination pharmacokinetic parameters were evaluated using nonlinear mixed effects modelling (nonmem)."( Polymorphisms of drug-metabolizing enzymes (GST, CYP2B6 and CYP3A) affect the pharmacokinetics of thiotepa and tepa.
Beijnen, JH; Doodeman, VD; Ekhart, C; Huitema, AD; Rodenhuis, S; Smits, PH, 2009
)
0.35

Compound-Compound Interactions

ExcerptReferenceRelevance
"A striking chemotherapeutically curative effect on tumor was obtained by means of temporary interruption of regional blood flow combined with local hyperthermia."( Temporary interruption of regional blood flow combined with local hyperthermia for cancer chemotherapy.
Aoki, K; Baba, T; Kanematsu, T; Kidera, Y; Kimura, M, 1976
)
0.26
" The aim of this study was to develop a population pharmacokinetic model describing the complex pharmacokinetics of CP, 4OHCP, 2DCECP, and PM when CP is administered in a high-dose combination with thiotepa and carboplatin."( Population pharmacokinetics of cyclophosphamide and its metabolites 4-hydroxycyclophosphamide, 2-dechloroethylcyclophosphamide, and phosphoramide mustard in a high-dose combination with Thiotepa and Carboplatin.
Beijnen, JH; de Jonge, ME; Huitema, AD; Rodenhuis, S; van Dam, SM, 2005
)
0.33

Dosage Studied

ExcerptRelevanceReference
" The great interindividual variation encountered in the serum pharmacokinetics of TEPA may be of clinical importance and represents a further indication that pharmacokinetically guided dosing of thio-TEPA could be valuable."( Long-term pharmacokinetics of thio-TEPA, TEPA and total alkylating activity following i.v. bolus administration of thio-TEPA in ovarian cancer patients.
Hagen, B; Neverdal, G; Nilsen, OG; Walstad, RA, 1990
)
0.28
" We advocate further investigation of this pharmacokinetic-pharmacodynamic relationship so as to establish individualized dosing of thio-TEPA."( Pharmacokinetics of thio-TEPA and TEPA in the conventional dose-range and its correlation to myelosuppressive effects.
Hagen, B, 1991
)
0.28
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
phosphoramideA compound in which one or more of the OH groups of phosphoric acid have been replaced with an amino or substituted amino group. The term is commonly confined to the phosphoric triamides, P(=O)(NR2)3, since replacement of one or two OH groups produces phosphoramidic acids: P(=O)(OH)(NR2)2 , P(=O)(OH)2(NR2).
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
DRattus norvegicus (Norway rat)IC50 (µMol)0.43000.00030.50267.7625AID61186
D(2) dopamine receptorRattus norvegicus (Norway rat)IC50 (µMol)0.22000.00010.54948.4000AID64451
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (14)

Assay IDTitleYearJournalArticle
AID153206Number of cures from P388 leukemia in CD2F1 male mice as tumor-free survivors after day 60.1986Journal of medicinal chemistry, Nov, Volume: 29, Issue:11
In the search for new anticancer drugs. 19. A predictive design of N,N:N',N':N'',N''-tri-1,2-ethanediylphosphorothioic triamide (TEPA) analogues.
AID153202Compound was tested for its antineoplastic activities against P388 leukemia in CD2F1 male mice.1986Journal of medicinal chemistry, Nov, Volume: 29, Issue:11
In the search for new anticancer drugs. 19. A predictive design of N,N:N',N':N'',N''-tri-1,2-ethanediylphosphorothioic triamide (TEPA) analogues.
AID153212Antineoplastic activity against P388 leukemia in CD2F1 male mice and the average percentage weight change on day 5 was measured.1986Journal of medicinal chemistry, Nov, Volume: 29, Issue:11
In the search for new anticancer drugs. 19. A predictive design of N,N:N',N':N'',N''-tri-1,2-ethanediylphosphorothioic triamide (TEPA) analogues.
AID122780Anticancer activity against P388 leukemia in CD2F1 male mice expressed as Average % weight change on day 5 as a measure of toxicity was reported at a dose of 6 mg/kg/day. 1986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
In the search for new anticancer drugs. 17. Linear and cyclic polyether analogues of N,N:N',N':N'',N''-tri-1,2-ethanediylphosphoric triamide and N,N:N',N':N'',N''-tri-1,2-ethanediylphosphorothioic triamide.
AID64451Inhibition of specific binding of [3H]spiroperidol to Dopamine receptor D2 in rat striatal membranes1998Journal of medicinal chemistry, Oct-08, Volume: 41, Issue:21
N-(Iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines: synthesis and adrenergic and dopaminergic activity studies.
AID120688Compound was evaluated for the anticancer activity against P388 leukemia in CD2F1 male mice at a dose of 6 mg/kg/day.1986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
In the search for new anticancer drugs. 17. Linear and cyclic polyether analogues of N,N:N',N':N'',N''-tri-1,2-ethanediylphosphoric triamide and N,N:N',N':N'',N''-tri-1,2-ethanediylphosphorothioic triamide.
AID122188Compound was evaluated for the anticancer activity against P388 leukemia in CD2F1 male mice at a dose of 5 mg/kg/after 30 days; 1/61986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
In the search for new anticancer drugs. 17. Linear and cyclic polyether analogues of N,N:N',N':N'',N''-tri-1,2-ethanediylphosphoric triamide and N,N:N',N':N'',N''-tri-1,2-ethanediylphosphorothioic triamide.
AID153210Antineoplastic activities against P388 leukemia in CD2F1 male mice.1986Journal of medicinal chemistry, Nov, Volume: 29, Issue:11
In the search for new anticancer drugs. 19. A predictive design of N,N:N',N':N'',N''-tri-1,2-ethanediylphosphorothioic triamide (TEPA) analogues.
AID235777Therapeutic ratio as optimum dose/dose ILS401986Journal of medicinal chemistry, Nov, Volume: 29, Issue:11
In the search for new anticancer drugs. 19. A predictive design of N,N:N',N':N'',N''-tri-1,2-ethanediylphosphorothioic triamide (TEPA) analogues.
AID115021Percentage increase in life span when the compound was administered intraperitoneally at dose of 6 mg/Kg in P388 leukemia in CDF1 mice was determined1986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
In the search for new anticancer drugs. 17. Linear and cyclic polyether analogues of N,N:N',N':N'',N''-tri-1,2-ethanediylphosphoric triamide and N,N:N',N':N'',N''-tri-1,2-ethanediylphosphorothioic triamide.
AID153200Antineoplastic activity against P388 leukemia in CD2F1 male mice and the percent increase in life span was measured on day 30.1986Journal of medicinal chemistry, Nov, Volume: 29, Issue:11
In the search for new anticancer drugs. 19. A predictive design of N,N:N',N':N'',N''-tri-1,2-ethanediylphosphorothioic triamide (TEPA) analogues.
AID61186Displacement of [3H]-SCH- 23390 from Dopamine receptor D1 of rat striatal membranes1998Journal of medicinal chemistry, Oct-08, Volume: 41, Issue:21
N-(Iodopropenyl)-octahydrobenzo[f]- and -[g]quinolines: synthesis and adrenergic and dopaminergic activity studies.
AID29763partition coefficient with the use of 1-octanol / water solvent system1986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
In the search for new anticancer drugs. 17. Linear and cyclic polyether analogues of N,N:N',N':N'',N''-tri-1,2-ethanediylphosphoric triamide and N,N:N',N':N'',N''-tri-1,2-ethanediylphosphorothioic triamide.
AID122191Compound was evaluated for the anticancer activity against P388 leukemia in CD2F1 male mice at a dose of 60 mg/kg/after 60 days; 0/61986Journal of medicinal chemistry, Jul, Volume: 29, Issue:7
In the search for new anticancer drugs. 17. Linear and cyclic polyether analogues of N,N:N',N':N'',N''-tri-1,2-ethanediylphosphoric triamide and N,N:N',N':N'',N''-tri-1,2-ethanediylphosphorothioic triamide.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (133)

TimeframeStudies, This Drug (%)All Drugs %
pre-199095 (71.43)18.7374
1990's15 (11.28)18.2507
2000's11 (8.27)29.6817
2010's5 (3.76)24.3611
2020's7 (5.26)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 14.73

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index14.73 (24.57)
Research Supply Index5.00 (2.92)
Research Growth Index4.55 (4.65)
Search Engine Demand Index10.37 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (14.73)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials7 (4.96%)5.53%
Reviews10 (7.09%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other124 (87.94%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]