T3DB: Thiotepa

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Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (1)XML

Targets (1)

Record Information

Version

2.0

Creation Date

2014-09-11 02:06:13 UTC

Update Date

2014-12-24 20:26:56 UTC

Accession Number

T3D4716

Identification

Common Name

Thiotepa

Class

Small Molecule

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). It is mostly used to treat breast cancer, ovarian cancer and bladder cancer. It is also used as conditioning for Bone marrow transplantation. Its main toxicity is myelosuppression.

Compound Type

Drug
Metabolite
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
Thioplex

Chemical Formula

C₆H₁₂N₃PS

Average Molecular Mass

189.218 g/mol

Monoisotopic Mass

189.049 g/mol

CAS Registry Number

52-24-4

IUPAC Name

tris(aziridin-1-yl)-λ⁵-phosphanethione

Traditional Name

thiophosphamide

SMILES

S=P(N1CC1)(N1CC1)N1CC1

InChI Identifier

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

InChI Key

InChIKey=FOCVUCIESVLUNU-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as organic thiophosphoric acids and derivatives. These are organic compounds containing the thiophosphoric acid functional group or a derivative thereof, with the general structure RP(R')(R'')=S, where R,R',R'' = O,N, halogen residue.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Organic thiophosphoric acids and derivatives

Sub Class

Not Available

Direct Parent

Organic thiophosphoric acids and derivatives

Alternative Parents

Substituents

Organic thiophosphoric acid or derivatives
Azacycle
Organoheterocyclic compound
Aziridine
Organic nitrogen compound
Organopnictogen compound
Hydrocarbon derivative
Organonitrogen compound
Aliphatic heteromonocyclic compound

Molecular Framework

Aliphatic heteromonocyclic compounds

External Descriptors

aziridines (CHEBI:9570 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	51.5°C
Boiling Point	Not Available
Solubility	1.9E+005 mg/L (at 25°C)
LogP	0.53

Predicted Properties

Property	Value	Source
Water Solubility	9.27 g/L	ALOGPS
logP	0.17	ALOGPS
logP	-1	ChemAxon
logS	-1.3	ALOGPS
pKa (Strongest Basic)	-0.3	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	9.03 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	50.72 m³·mol⁻¹	ChemAxon
Polarizability	18.23 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0007-9700000000-870c297591c0a9b9707c	JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	JSpectraViewer
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-0udj-2910000000-ba7d9f76d09c90907cd5	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-0udj-2910000000-ba7d9f76d09c90907cd5	JSpectraViewer \| MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0006-0900000000-0cd73bb1e3f4935cf116	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0005-3900000000-5c3374f9826ed342ca4e	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9000000000-8dc6d03ec98f9c80f9d2	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000i-2900000000-bb1e4366af9868c15a01	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-074s-0900000000-dc8c896ef045e2852518	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9100000000-7251e3acc37a1500dc98	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0002-0900000000-1123ba8976a8239bb663	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0002-0900000000-103f3980559601ae7672	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0f6x-9700000000-b8be72202a635e78e521	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000i-0900000000-460ca1d15e5d5215d31f	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-000i-0900000000-acd27824890aefdaae3f	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9700000000-601e44410bd7bac39398	JSpectraViewer
MS	Mass Spectrum (Electron Ionization)	splash10-00kn-6900000000-6d6b7c109663ea65ad79	JSpectraViewer \| MoNA
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

The alkyl group is attached to the guanine base of DNA, at the number 7 nitrogen atom of the imidazole ring. They stop tumor growth by crosslinking guanine nucleobases in DNA double-helix strands, directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. These drugs act nonspecifically.

Metabolism

Route of Elimination: Urinary excretion of 14C-labeled thiotepa and metabolites in a 34-year old patient with metastatic carcinoma of the cecum who received a dose of 0.3 mg/kg intravenously was 63%. Half Life: 1.5 to 4.1 hours

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

1, carcinogenic to humans. (2)

Uses/Sources

ThioTEPA is used a as conditioning treatment prior to allogeneic or autologous haematopoietic progenitor cell transplantation (HPCT) in haematological diseases in adult and paediatric patients. Also, when high dose chemotherapy with HPCT support it is appropriate for the treatment of solid tumours in adult and paediatric patients.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

128310

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Thiotepa

References

Synthesis Reference

John Kazan, “Process for producing thiotepa.” U.S. Patent US4918199, issued February, 1954.

MSDS

T3D4716.pdf

General References

Maanen MJ, Smeets CJ, Beijnen JH: Chemistry, pharmacology and pharmacokinetics of N,N',N" -triethylenethiophosphoramide (ThioTEPA). Cancer Treat Rev. 2000 Aug;26(4):257-68. [10913381 ]
International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

1. DNA

General Function:: Used for biological information storage.
Specific Function:: DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:: 2.15 x 10¹² Da

References

Gor PP, Su HI, Gray RJ, Gimotty PA, Horn M, Aplenc R, Vaughan WP, Tallman MS, Rebbeck TR, DeMichele A: Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study. Breast Cancer Res. 2010;12(3):R26. doi: 10.1186/bcr2570. Epub 2010 May 10. [20459744 ]
Lee PC, Kakadiya R, Su TL, Lee TC: Combination of bifunctional alkylating agent and arsenic trioxide synergistically suppresses the growth of drug-resistant tumor cells. Neoplasia. 2010 May;12(5):376-87. [20454509 ]
Lestuzzi C: Neoplastic pericardial disease: Old and current strategies for diagnosis and management. World J Cardiol. 2010 Sep 26;2(9):270-9. doi: 10.4330/wjc.v2.i9.270. [21160603 ]
Maanen MJ, Smeets CJ, Beijnen JH: Chemistry, pharmacology and pharmacokinetics of N,N',N" -triethylenethiophosphoramide (ThioTEPA). Cancer Treat Rev. 2000 Aug;26(4):257-68. [10913381 ]

Thiotepa (T3D4716)

Structure for T3D4716: Thiotepa

Targets

References