Details of the Drug

General Information of Drug (ID: DMIZKOP)

Drug Name
Thiotepa
Synonyms
thiotepa; THIO-TEPA; 52-24-4; Triethylenethiophosphoramide; Thiophosphamide; Tiofosyl; Tiofosfamid; Thiofozil; Tiofozil; Thioplex; Tespamin; Oncotepa; Tespamine; Girostan; Thiotef; Stepa; Tio-tef; Thio-Tep; Oncotiotepa; Tifosyl; Oncothio-tepa; TESPA; TSPA; Thio-tepa S; Ledertepa; Thiotriethylenephosphoramide; TIO TEF; N,N',N''-Triethylenethiophosphoramide; Tris(1-aziridinyl)phosphine sulfide; Thiophosphamidum; 1,1',1''-phosphorothioyltriaziridine; Triethylene thiophosphoramide; Triaziridinylphosphine sulfide
Indication
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [1]
Immunodeficiency 4A00-4A85 Approved [2]
Leukemia N.A. Approved [2]
Urinary bladder cancer N.A. Approved [2]
Classic Hodgkin lymphoma N.A. Investigative [2]
Neuroblastoma 2D11.2 Investigative [2]
⏷ Show the Full List of Indication(s)
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 189.22
Logarithm of the Partition Coefficient (xlogp) 0.5
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 4
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
Clearance
The drug present in the plasma can be removed from the body at the rate of 6.7 mL/min/kg [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 1.5 - 4.1 hours [4]
Unbound Fraction
The unbound fraction of drug in plasma is 0.9% [4]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.6 L/kg [4]
Chemical Identifiers
Formula
C6H12N3PS
IUPAC Name
tris(aziridin-1-yl)-sulfanylidene-lambda5-phosphane
Canonical SMILES
C1CN1P(=S)(N2CC2)N3CC3
InChI
InChI=1S/C6H12N3PS/c11-10(7-1-2-7,8-3-4-8)9-5-6-9/h1-6H2
InChIKey
FOCVUCIESVLUNU-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
5453
ChEBI ID
CHEBI:9570
CAS Number
52-24-4
DrugBank ID
DB04572
TTD ID
D00YZA
VARIDT ID
DR00862
INTEDE ID
DR1583
ACDINA ID
D01482
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [5]
Glutathione S-transferase alpha-1 (GSTA1) DE4ZHS1 GSTA1_HUMAN Substrate [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
14-3-3 protein theta OTWG7F3H 1433T_HUMAN Gene/Protein Processing [7]
Aldehyde dehydrogenase 1A1 (ALDH1A1) OTCUWZKB AL1A1_HUMAN Drug Response [8]
Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) OTAYZZE6 AL3A1_HUMAN Drug Response [8]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Gene/Protein Processing [7]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [7]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Gene/Protein Processing [7]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Gene/Protein Processing [7]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Gene/Protein Processing [7]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Gene/Protein Processing [7]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Gene/Protein Processing [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Thiotepa (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
ABT-492 DMJFD2I Minor Decreased absorption of Thiotepa due to intestinal mucosa variation caused by ABT-492. Bacterial infection [1A00-1C4Z] [10]
Teriflunomide DMQ2FKJ Major Additive immunosuppressive effects by the combination of Thiotepa and Teriflunomide. Hyper-lipoproteinaemia [5C80] [11]
Denosumab DMNI0KO Moderate Additive myelosuppressive effects by the combination of Thiotepa and Denosumab. Low bone mass disorder [FB83] [12]
Tecfidera DM2OVDT Moderate Additive immunosuppressive effects by the combination of Thiotepa and Tecfidera. Multiple sclerosis [8A40] [13]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Thiotepa and Siponimod. Multiple sclerosis [8A40] [14]
Fingolimod DM5JVAN Major Additive immunosuppressive effects by the combination of Thiotepa and Fingolimod. Multiple sclerosis [8A40] [15]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Thiotepa and Ocrelizumab. Multiple sclerosis [8A40] [16]
Ozanimod DMT6AM2 Major Additive immunosuppressive effects by the combination of Thiotepa and Ozanimod. Multiple sclerosis [8A40] [17]
Omacetaxine mepesuccinate DMPU2WX Moderate Additive immunosuppressive effects by the combination of Thiotepa and Omacetaxine mepesuccinate. Myeloproliferative neoplasm [2A20] [18]
Abametapir DM2RX0I Moderate Decreased metabolism of Thiotepa caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [19]
Lefamulin DME6G97 Moderate Decreased metabolism of Thiotepa caused by Lefamulin mediated inhibition of CYP450 enzyme. Pneumonia [CA40] [20]
Canakinumab DM8HLO5 Moderate Additive immunosuppressive effects by the combination of Thiotepa and Canakinumab. Rheumatoid arthritis [FA20] [21]
Rilonacept DMGLUQS Moderate Additive immunosuppressive effects by the combination of Thiotepa and Rilonacept. Rheumatoid arthritis [FA20] [21]
Golimumab DMHZV7X Major Additive immunosuppressive effects by the combination of Thiotepa and Golimumab. Rheumatoid arthritis [FA20] [22]
Anthrax vaccine DM9GSWY Moderate Antagonize the effect of Thiotepa when combined with Anthrax vaccine. Sepsis [1G40-1G41] [23]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Thiotepa caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [17]
Larotrectinib DM26CQR Moderate Decreased metabolism of Thiotepa caused by Larotrectinib mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [14]
LEE011 DMMX75K Moderate Decreased metabolism of Thiotepa caused by LEE011 mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [24]
Fostamatinib DM6AUHV Moderate Decreased metabolism of Thiotepa caused by Fostamatinib mediated inhibition of CYP450 enzyme. Thrombocytopenia [3B64] [25]
⏷ Show the Full List of 19 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Water E00035 962 Solvent
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Thiotepa 15mg lyophilized powder 15mg Lyophilized Powder Intravenous
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7622).
2 Thiotepa FDA Label
3 BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 Cytochrome P450 isozymes 3A4 and 2B6 are involved in the in vitro human metabolism of thiotepa to TEPA. Cancer Chemother Pharmacol. 2002 Jun;49(6):461-7.
6 Differential catalytic efficiency of allelic variants of human glutathione S-transferase Pi in catalyzing the glutathione conjugation of thiotepa. Arch Biochem Biophys. 1999 Jun 1;366(1):89-94.
7 Susceptibility to drug-induced apoptosis correlates with differential modulation of Bad, Bcl-2 and Bcl-xL protein levels. Cell Death Differ. 2000 Jun;7(6):574-86. doi: 10.1038/sj.cdd.4400688.
8 Relations between polymorphisms in drug-metabolising enzymes and toxicity of chemotherapy with cyclophosphamide, thiotepa and carboplatin. Pharmacogenet Genomics. 2008 Nov;18(11):1009-15. doi: 10.1097/FPC.0b013e328313aaa4.
9 The naturally occurring cytochrome P450 (P450) 2B6 K262R mutant of P450 2B6 exhibits alterations in substrate metabolism and inactivation. Drug Metab Dispos. 2005 Jun;33(6):795-802.
10 Johnson EJ, MacGowan AP, Potter MN, et al "Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy." J Antimicrob Chemother 25 (1990): 837-42. [PMID: 2373666]
11 Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
12 Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
13 Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
14 Cerner Multum, Inc. "Australian Product Information.".
15 Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
16 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
17 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
18 Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
19 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
20 Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
21 Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
22 Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
23 CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]
24 DSouza DL, Levasseur LM, Nezamis J, Robbins DK, Simms L, Koch KM "Effect of alosetron on the pharmacokinetics of alprazolam." J Clin Pharmacol 41 (2001): 452-4. [PMID: 11304902]
25 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.