Identification

Name
Thiotepa
Accession Number
DB04572
Type
Small Molecule
Groups
Approved, Investigational
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.

Structure
Thumb
Synonyms
Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TepadinaPowder, for solution100 mgIntravenousADIENNE SA2017-10-31Not applicableCanada
TepadinaInjection, powder, for solution100 mg/1Intracavitary; Intravenous; IntravesicalAmneal Biosciences Llc2017-08-15Not applicableUs
TepadinaPowder, for solution15 mgIntravenousADIENNE SA2017-11-06Not applicableCanada
TepadinaInjection, powder, for solution100 mg/1Intracavitary; Intravenous; IntravesicalADIENNE SA2017-01-26Not applicableUs
TepadinaInjection, powder, for solution15 mg/1Intracavitary; Intravenous; IntravesicalAmneal Biosciences Llc2017-08-15Not applicableUs
TepadinaInjection, powder, for solution15 mg/1Intracavitary; Intravenous; IntravesicalADIENNE SA2017-01-26Not applicableUs
Thio Tepa Inj 15mg/vialPowder, for solution15 mgOral; Rectal; VaginalLederle Cyanamid Canada Inc.1959-12-311997-11-24Canada
Thiotepa - (pws 15 Mg/vial)Powder, for solution15 mgIntracavitary; Intravenous; IntravesicalWyeth Ltd.1997-08-252004-09-15Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ThiotepaInjection, powder, lyophilized, for solution15 mg/1.5mLIntracavitary; Intravenous; IntravesicalWest-Ward Pharmaceuticals Corp2001-06-01Not applicableUs
ThiotepaInjection, powder, lyophilized, for solution15 mg/1.5mLIntracavitary; Intravenous; IntravesicalBedford Pharmaceuticals2001-06-012012-09-30Us
ThiotepaInjection, powder, lyophilized, for solution15 mg/1Intracavitary; Intravenous; IntravesicalDr.Reddy's Laboratories Inc.,2018-05-04Not applicableUs
ThiotepaInjection, powder, lyophilized, for solution15 mg/1.5mLIntracavitary; Intravenous; IntravesicalSagent Pharmaceuticals2018-06-15Not applicableUs
ThiotepaInjection, powder, lyophilized, for solution15 mg/1.5mLIntracavitary; Intravenous; IntravesicalWest-Ward Pharmaceuticals Corp2001-06-01Not applicableUs
International/Other Brands
Thioplex
Categories
UNII
905Z5W3GKH
CAS number
52-24-4
Weight
Average: 189.218
Monoisotopic: 189.048954601
Chemical Formula
C6H12N3PS
InChI Key
FOCVUCIESVLUNU-UHFFFAOYSA-N
InChI
InChI=1S/C6H12N3PS/c11-10(7-1-2-7,8-3-4-8)9-5-6-9/h1-6H2
IUPAC Name
tris(aziridin-1-yl)-λ⁵-phosphanethione
SMILES
S=P(N1CC1)(N1CC1)N1CC1

Pharmacology

Indication

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.

Associated Conditions
Pharmacodynamics

The unstable nitrogen-carbon groups alkylate with DNA causing irrepairable DNA damage. 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.

Mechanism of action

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.

TargetActionsOrganism
ADNA
cross-linking/alkylation
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
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

Clearance
  • 446 +/- 63 mL/min [female patients (45 to 84 years) with advanced stage ovarian cancer receiving 60 mg and 80 mg thiotepa by intravenous infusion on subsequent courses given at 4-week intervals]
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Thiotepa.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Thiotepa.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Thiotepa.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Thiotepa.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Thiotepa.
5-androstenedioneThe metabolism of Thiotepa can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Thiotepa can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Thiotepa.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Thiotepa is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Thiotepa.
Food Interactions
Not Available

References

Synthesis Reference

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

US4918199
General References
  1. 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. [PubMed:10913381]
External Links
Human Metabolome Database
HMDB0015576
KEGG Drug
D00583
KEGG Compound
C07641
PubChem Compound
5453
PubChem Substance
46505958
ChemSpider
5254
BindingDB
50418086
ChEBI
9570
ChEMBL
CHEMBL671
PharmGKB
PA451668
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Thiotepa
ATC Codes
L01AC01 — Thiotepa
AHFS Codes
  • 10:00.00 — Antineoplastic Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingTreatmentNeuroblastomas1
0TerminatedTreatmentAllogeneic peripheral haematopoietic stem cell transplant / Neuroepithelial Tumor / Tumors, Solid1
1CompletedTreatmentAcute Lymphocytic Leukemia (ALL) / Acute Myelogenous Leukaemia (AML) / Leukemias / Myelodysplastic Syndrome1
1CompletedTreatmentBrain and Central Nervous System Tumors1
1CompletedTreatmentCancer of the Ovary2
1CompletedTreatmentCancer, Breast1
1CompletedTreatmentChronic Myeloproliferative Disorders / Leukemias / Malignant Lymphomas / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms1
1CompletedTreatmentCongenital Amegakaryocytic Thrombocytopenia / Leukemias / Myelodysplastic Syndromes / Severe Congenital Neutropenia1
1CompletedTreatmentCongenital Marrow Failures / Haemoglobinopathies congenital / Immunodeficiencies / Inborn Errors of Metabolism / Lysosomal Storage Diseases / Non Malignant Disorders / Sickle Cell / Thalassaemic disorders1
1CompletedTreatmentLeukemias1
1CompletedTreatmentLeukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes1
1CompletedTreatmentMalignancies, Hematologic1
1CompletedTreatmentNeoplasms, Brain / Neuroblastomas / Sarcomas / Tumors, Central Nervous System1
1CompletedTreatmentSarcomas1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1CompletedTreatmentWiskott-Aldrich Syndrome (WAS)1
1RecruitingTreatmentAgnogenic Myeloid Metaplasia / Hematological Diseases / Immune Deficiencies / Malignant Lymphomas / Multiple Myeloma (MM) / Tumors, Solid1
1RecruitingTreatmentGraft Versus Host Disease (GVHD) / Sickle Cell Disorders1
1TerminatedSupportive CareBrain and Central Nervous System Tumors / Cancer of the Ovary / Childhood Germ Cell Tumor / Chordomas / Liver Cancer / Neuroblastomas / Renal Cancers / Retinoblastoma / Sarcomas1
1TerminatedTreatmentBrain and Central Nervous System Tumors / Liver Cancer / Renal Cancers / Retinoblastoma / Sarcomas1
1Unknown StatusTreatmentCancer, Breast1
1Unknown StatusTreatmentLeukemias / Myelodysplastic Syndromes1
1Unknown StatusTreatmentUnspecified Childhood Solid Tumor, Protocol Specific1
1WithdrawnTreatmentLeukemias / Malignant Lymphomas / Pediatric Disorders / Transplantation, Stem Cell1
1, 2Active Not RecruitingTreatmentGraft Versus Host Disease (GVHD) / Leukemias / Myelodysplastic Syndromes1
1, 2CompletedTreatmentCancer of the Ovary1
1, 2CompletedTreatmentCancer, Breast1
1, 2CompletedTreatmentLeukemias / Myelodysplastic Syndromes1
1, 2CompletedTreatmentMalignancies, Hematologic1
1, 2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myelogenous Leukaemia (AML) / Chronic Myeloid Leukemia (CML) / Juvenile Myelomonocytic Leukemia (JMML) / Lymphoma (Hodgkin's and Non-Hodgkin's) / Myelodysplastic Syndromes (MDS)1
1, 2RecruitingTreatmentBeta-Thalassemia Major / Congenital Hypoplastic Anemia / Sickle Cell Disorders1
1, 2RecruitingTreatmentCrohn's Disease (CD)1
1, 2RecruitingTreatmentEmphysema or COPD / Idiopathic Pulmonary Fibrosis (IPF)1
1, 2RecruitingTreatmentHigh-risk Medulloblastoma1
1, 2RecruitingTreatmentSevere Combined Immunodeficiency1
1, 2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myelogenous Leukaemia (AML) / Blood and Marrow Transplant (BMT) / Chronic Chronic myelogenous leukemia / Chronic Lymphocytic Leukaemia (CLL) / Leukemia Chronic Myelogenous Leukemia (CML) / Leukemia, Acute / Leukemias / Lymphomas: Non-Hodgkin / Myelodysplastic Syndromes (MDS) / Non-Hodgkin's Lymphoma (NHL)1
1, 2TerminatedTreatmentAnemias / Immunodeficiencies / Leukemias / Malignant Lymphomas / Neuroblastomas1
1, 2TerminatedTreatmentChronic Myelogenous (or Myeloid) Leukemia (CML) Resistant to STI Therapy / Leukemia, Acute / Lymphoma, Hodgkins / Malignancies, Hematologic / Myelodysplastic Syndromes (MDS) Other Than RA or RARS Subtypes / Non-Hodgkin's Lymphoma (NHL) / Plasma Cell Myeloma1
1, 2Unknown StatusTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
1, 2Unknown StatusTreatmentCancer, Breast2
1, 2WithdrawnTreatmentCancer, Breast1
1, 2WithdrawnTreatmentMalignant Lymphomas1
2Active Not RecruitingOtherMyeloid Leukemias1
2Active Not RecruitingTreatmentAccelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Acute Biphenotypic Leukemia (ABL) / Acute Leukemias of Ambiguous Lineage / Acute myeloid leukaemia (in remission) / Acute Undifferentiated Leukemia (AUL) / Adult Acute Lymphoblastic Leukemia in Remission / Adult Acute Myeloid Leukemia in Remission / Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Childhood Acute Lymphoblastic Leukemia in Remission / Childhood Acute Myeloid Leukemia in Remission / Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Myelodysplastic Syndrome With Excess Blasts-1 / Myelodysplastic Syndrome With Excess Blasts-2 / RAEB-1 / RAEB-2 / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia / Recurrent Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Myeloid Leukemia / Refractory Adult Acute Lymphoblastic Leukemia / Refractory Anemia With Excess Blasts / Refractory Childhood Acute Lymphoblastic Leukemia1
2Active Not RecruitingTreatmentAcute Biphenotypic Leukemia (ABL) / Acute erythroid leukemia / Acute Lymphoblastic Leukemia in Remission / Acute Megakaryoblastic Leukemia / Acute myeloid leukaemia (in remission) / Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome / Blasts Under 10 Percent of Bone Marrow Nucleated Cells / Blasts Under 5 Percent of Bone Marrow Nucleated Cells / Chronic Chronic myelogenous leukemia / Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Mixed Phenotype Acute Leukemia (MPAL) / Myelodysplastic Syndrome / Myelodysplastic Syndrome With Excess Blasts / Pancytopenia / Refractory Anemia / Refractory Anemia With Excess Blasts / Refractory Anemia With Excess Blasts in Transformation / Secondary Acute Myeloid Leukemia (Secondary AML, sAML)1
2Active Not RecruitingTreatmentCNS brain / Cns Cancer1
2Active Not RecruitingTreatmentGraft Versus Host Disease (GVHD) / Leukemias / Myelodysplastic Syndromes1
2Active Not RecruitingTreatmentHemoglobinuria, Paroxysmal Nocturnal (PNH) / Juvenile Myelomonocytic Leukemia (JMML) / Leukemia Acute Myeloid Leukemia (AML) / Leukemia, Acute Lymphocytic (ALL) / Leukemia, Myeloid, Chronic(CML) / Lymphoma, Hodgkins / Lymphoma, Non-Hodgkin (NHL) / Myelodysplastic Syndromes (MDS)1
2Active Not RecruitingTreatmentHigh Risk Neuroblastoma1
2Active Not RecruitingTreatmentLeukemias / Malignant Lymphomas / Transplantation, Stem Cell1
2Active Not RecruitingTreatmentMalignant Lymphomas1
2Active Not RecruitingTreatmentSarcoma, Osteogenic1
2CompletedTreatmentAcute Lymphocytic Leukemia (ALL) / Chronic Myeloid Leukemia (CML) / Histiocytosis / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplasia1
2CompletedTreatmentBeta Thalassemia / Bone Marrow Failure / Histiocytosis / Immunodeficiencies / Inborn Errors of Metabolism / Leukemias / Malignant Lymphomas / Sickle Cell Disorders1
2CompletedTreatmentBlood Stem Cell Transplant Failure / Leukemias / Malignancies, Hematologic1
2CompletedTreatmentBrain and Central Nervous System Tumors4
2CompletedTreatmentBrain and Central Nervous System Tumors / Cancer of the Ovary / Childhood Germ Cell Tumor / Extragonadal Germ Cell Tumor / Retinoblastoma / Testicular germ cell tumour / Unspecified Adult Solid Tumor, Protocol Specific / Unspecified Childhood Solid Tumor, Protocol Specific1
2CompletedTreatmentBrain and Central Nervous System Tumors / Head and Neck Carcinoma / Malignant Lymphomas1
2CompletedTreatmentBrain and Central Nervous System Tumors / Neuroblastomas1
2CompletedTreatmentCancer of the Ovary / Childhood Germ Cell Tumor / Extragonadal Germ Cell Tumor / Head and Neck Carcinoma / Liver Cancer / Malignant Lymphomas / Neuroblastomas / Renal Cancers / Retinoblastoma / Sarcomas / Testicular germ cell tumour1
2CompletedTreatmentCancer, Breast7
2CompletedTreatmentCancer, Breast / Drug/Agent Toxicity by Tissue/Organ1
2CompletedTreatmentCancer, Breast / Invasive Breast Carcinoma / Metastatic Breast Carcinoma1
2CompletedTreatmentCancer, Breast / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Testicular germ cell tumour / Unspecified Adult Solid Tumor, Protocol Specific / Unspecified Childhood Solid Tumor, Protocol Specific1
2CompletedTreatmentCentral Nervous System Lymphoma1
2CompletedTreatmentChildhood Germ Cell Tumor / Neoplasms, Brain / Tumors, Central Nervous System1
2CompletedTreatmentChronic Myeloid Leukemia (CML) / Leukemia, Lymphocytic, Acute / Leukemia, Myelocytic, Acute / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentEstrogen Receptor-negative Breast Cancer / Estrogen Receptor-Positive Breast Cancer / Inflammatory carcinoma of the breast / Male Breast Cancer / Progesterone Receptor-negative Breast Cancer / Progesterone Receptor-positive Breast Cancer / Stage IIIB Breast Cancer / Stage IV Breast Cancer1
2CompletedTreatmentGraft Versus Host Disease (GVHD) / Leukemias / Myelodysplastic Syndromes1
2CompletedTreatmentLeukemias1
2CompletedTreatmentLeukemias / Malignant Lymphomas2
2CompletedTreatmentLeukemias / Malignant Lymphomas / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms2
2CompletedTreatmentMalignant Lymphomas2
2CompletedTreatmentMalignant Lymphomas / Unspecified Adult Solid Tumor, Protocol Specific / Unspecified Childhood Solid Tumor, Protocol Specific1
2CompletedTreatmentMetastatic, Cerebral Primitive Neuroectodermal Tumors1
2CompletedTreatmentMultiple Myeloma and Plasma Cell Neoplasm1
2CompletedTreatmentNeuroblastomas3
2CompletedTreatmentSarcomas1
2Not Yet RecruitingTreatmentMalignant Lymphomas1
2Not Yet RecruitingTreatmentVery High Risk Neuroblastoma1
2RecruitingTreatmentAccelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Acute Biphenotypic Leukemia (ABL) / Acute Leukemias of Ambiguous Lineage / Acute Undifferentiated Leukemia (AUL) / Adult Acute Lymphoblastic Leukemia in Remission / Adult Acute Myeloid Leukemia in Remission / Allogeneic Hematopoietic Stem Cell Transplantation Recipient / Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) / Childhood Acute Lymphoblastic Leukemia in Remission / Childhood Acute Myeloid Leukemia in Remission / Donor / Graft Versus Host Disease (GVHD) / Lymphoma, Lymphoblastic / Myelodysplastic Syndrome With Excess Blasts / Myelodysplastic Syndrome With Excess Blasts-1 / Myelodysplastic Syndrome With Excess Blasts-2 / RAEB-1 / RAEB-2 / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia / Recurrent Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Myeloid Leukemia / Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Refractory Acute Lymphoblastic Leukemia / Refractory Acute Myeloid Leukemia / Refractory Anemia With Excess Blasts1
2RecruitingTreatmentAccelerated Phase Chronic Myelogenous Leukemia / Adult Acute Lymphoblastic Leukemia in Remission / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Nasal Type Extranodal NK/T-Cell Lymphoma / Anaplastic Large Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Blastic Phase Chronic Myelogenous Leukemia / Childhood Acute Lymphoblastic Leukemia in Remission / Childhood Burkitt Lymphoma / Childhood Chronic Myelogenous Leukemia / Childhood Diffuse Large Cell Lymphoma / Childhood Immunoblastic Large Cell Lymphoma / Childhood Myelodysplastic Syndromes / Childhood Nasal Type Extranodal NK/T-cell Lymphoma / Chronic Myelomonocytic Leukemia / Chronic Phase Chronic Myelogenous Leukemia / Cutaneous B-Cell Non-Hodgkin Lymphoma / De Novo Myelodysplastic Syndromes / Essential Thrombocythemia (ET) / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Hepatosplenic T-Cell Lymphoma / Intraocular Lymphoma / Juvenile Myelomonocytic Leukemia / Nodal marginal zone B-cell lymphomas / Noncutaneous Extranodal Lymphoma / Peripheral T-Cell Lymphoma (PTCL) / Polycythemia Vera (PV) / Post Transplant Lymphoproliferative Disorder / Previously Treated Myelodysplastic Syndromes / Primary Myelofibrosis / Recurrent Adult Acute Myeloid Leukemia / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Adult T-Cell Leukemia/Lymphoma / Recurrent Childhood Acute Myeloid Leukemia / Recurrent Childhood Anaplastic Large Cell Lymphoma / Recurrent Childhood Grade III Lymphomatoid Granulomatosis / Recurrent Childhood Large Cell Lymphoma / Recurrent Childhood Lymphoblastic Lymphoma / Recurrent Childhood Small Noncleaved Cell Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Recurrent Small Lymphocytic Lymphoma / Recurrent/Refractory Childhood Hodgkin Lymphoma / Refractory Anemia With Excess Blasts / Refractory Anemia With Excess Blasts in Transformation / Refractory Cytopenia With Multilineage Dysplasia / Refractory Hairy Cell Leukemia / Refractory Multiple Myeloma / Relapsing Chronic Myelogenous Leukemia / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Small Intestine Lymphoma / Splenic Marginal Zone Lymphoma / T-Cell Large Granular Lymphocyte Leukemia / Testicular Lymphoma / Waldenström's Macroglobulinemia (WM)1
2RecruitingTreatmentAcute Biphenotypic Leukemia (ABL) / Acute Lymphoblastic Leukaemias (ALL) / Acute Lymphoblastic Leukemia in Remission / Acute myeloid leukaemia (in remission) / Blasts Under 10 Percent of Bone Marrow Nucleated Cells / Blasts Under 5 Percent of Bone Marrow Nucleated Cells / Chromosome Abnormalities / Chronic Chronic myelogenous leukemia / Chronic Myelogenous Leukemia, BCR-ABL1 Positive / High Risk Myelodysplastic Syndrome / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome With Excess Blasts / Myelodysplastic Syndromes / Pancytopenia / Refractory Anemia1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Myelogenous Leukaemia (AML) / Multiple Myeloma (MM) / Myelodysplastic Syndrome1
2RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / Chronic Myeloid Leukemia (CML) / Granulocytic Sarcoma / Juvenile Myelomonocytic Leukemia (JMML) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes (MDS) / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentAcute Lymphocytic Leukemia (ALL) / Chronic Lymphocytic Leukaemia (CLL) / Chronic Myeloid Leukemia (CML) / Leukemia Acute Myeloid Leukemia (AML) / Lymphoma, Hodgkins / Multiple Myeloma (MM) / Myelodysplastic Syndrome / Myeloproliferative Syndromes / Non-Hodgkin's Lymphoma (NHL) / Other Diseases of Blood and Blood-Forming Organs1
2RecruitingTreatmentAcute Lymphocytic Leukemia (ALL) / Chronic Lymphocytic Leukaemia (CLL) / Chronic Myeloid Leukemia (CML) / Leukemia Acute Myeloid Leukemia (AML) / Lymphoma, Hodgkins / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentCancer of the Ovary / Childhood Germ Cell Tumor / Teratoma1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Lymphoma, Hodgkins / Multiple Myeloma (MM) / Non Hodgkin Lymphoma (NHL)1
2RecruitingTreatmentCongenital Bone Marrow Failure Syndromes / Hereditary Anemias / Inflammatory Conditions / Inherited Metabolic Disorders (IMD) / Patients With Sickle Disease Presenting Specific Symptoms / Primary Immunodeficiency (PID) / Primary Immunodeficiency Syndromes1
2RecruitingTreatmentDiffuse Sclerosis Systemic / Interstitial Lung Disease (ILD) / Pulmonary Hypertension (PH) / Sclerosis, Progressive Systemic1
2RecruitingTreatmentHematopoietic Stem Cell Transplant (HSCT) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes (MDS)1
2RecruitingTreatmentIntracranial Non-germinomatous Germ Cell Tumor1
2RecruitingTreatmentLeukemias1
2RecruitingTreatmentLeukemias / Malignant Lymphomas1
2RecruitingTreatmentLeukemias / Multiple Myeloma (MM) / Myelodysplastic Syndrome / Non-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2RecruitingTreatmentNeuroblastomas1
2RecruitingTreatmentNon-malignant Hematologic Disorders1
2RecruitingTreatmentRetinoblastoma1
2RecruitingTreatmentSickle Cell Disorders2
2RecruitingTreatmentUnresectable Localized Soft Tissue Sarcoma1
2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Chronic Lymphocytic Leukaemia (CLL) / Hodgkins Disease (HD) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes / Non-Hodgkin's Lymphoma (NHL)1
2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Chronic Myeloid Leukemia (CML) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplasia1
2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Chronic Chronic myelogenous leukemia / Granulocytic Sarcoma / Juvenile Myelomonocytic Leukemia (JMML) / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes (MDS) / Non-Hodgkin's Lymphoma (NHL)1
2TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia Acute Myeloid Leukemia (AML)1
2TerminatedTreatmentCancer of the Ovary / Childhood Germ Cell Tumor / Extragonadal Germ Cell Tumor / Testicular germ cell tumour1
2TerminatedTreatmentChronic Myeloproliferative Disorders / Leukemias / Myelodysplastic/Myeloproliferative Diseases1
2TerminatedTreatmentHaematological Malignancies1
2TerminatedTreatmentLeukemias / Myelodysplastic Syndromes1
2Unknown StatusPreventionGraft Versus Host Disease (GVHD)1
2Unknown StatusTreatmentBrain and Central Nervous System Tumors2
2Unknown StatusTreatmentBrain and Central Nervous System Tumors / Lymphoproliferative Disorders / Malignant Lymphomas / Small Intestine Cancer1
2Unknown StatusTreatmentCancer, Breast1
2Unknown StatusTreatmentMalignant Lymphomas1
2Unknown StatusTreatmentMedulloblastomas / Neoplasms, Brain / Neuroectodermal Tumors, Primitive1
2Unknown StatusTreatmentNeoplasms, Brain1
2Unknown StatusTreatmentNon-Hodgkin's Lymphoma (NHL)1
2Unknown StatusTreatmentPrimary Non Hodgkin Lymphoma of the Central Nervous System1
2Unknown StatusTreatmentRefractory Follicular Lymphoma1
2WithdrawnTreatmentAdult Acute Erythroid Leukemia / Adult Acute Monoblastic and Acute Monocytic Leukemia / Adult Acute Myeloid Leukemia1
2WithdrawnTreatmentBrain and Central Nervous System Tumors / Neuroblastomas / Retinoblastoma / Sarcomas1
2, 3Active Not RecruitingTreatmentCancer, Breast1
2, 3Active Not RecruitingTreatmentChronic Myeloproliferative Disorders / Leukemias / Malignant Lymphomas / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Diseases / Nonmalignant Neoplasm / Unspecified Adult Solid Tumor, Protocol Specific / Unspecified Childhood Solid Tumor, Protocol Specific1
2, 3CompletedTreatmentEpendymomas / Medulloblastomas / Recurrent Brain Tumors / Supratentorial PNETs1
2, 3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
2, 3RecruitingTreatmentChronic Myeloid Leukemia (CML)1
2, 3TerminatedTreatmentCancer, Breast1
3Active Not RecruitingTreatmentB-cell Childhood Acute Lymphoblastic Leukemia / Childhood Acute Lymphoblastic Leukemia in Remission / Graft Versus Host Disease (GVHD) / L1 Childhood Acute Lymphoblastic Leukemia / L2 Childhood Acute Lymphoblastic Leukemia / T-cell Childhood Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentChildhood Atypical Teratoid/Rhabdoid Tumor1
3Active Not RecruitingTreatmentExtraocular Retinoblastoma1
3Active Not RecruitingTreatmentLocalized Resectable Neuroblastoma / Localized Unresectable Neuroblastoma / Recurrent Neuroblastoma / Regional Neuroblastoma / Stage 4 Neuroblastoma / Stage 4S Neuroblastoma1
3Active Not RecruitingTreatmentLymphoblastic Leukemia, Acute, Childhood2
3CompletedTreatmentCancer, Breast5
3CompletedTreatmentLeukemias1
3CompletedTreatmentNeoplasms, Brain / Tumors, Central Nervous System1
3CompletedTreatmentUntreated Childhood Medulloblastoma / Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor1
3RecruitingTreatmentCancer, Breast1
3RecruitingTreatmentChildhood Ganglioneuroblastoma / Childhood Neuroblastoma / INRG Stage L2 / INRG Stage M / INRG Stage MS / NMYC Gene Amplification / Recurrent Neuroblastoma1
3TerminatedTreatmentCancer, Breast1
3Unknown StatusTreatmentBrain and Central Nervous System Tumors1
3Unknown StatusTreatmentCancer, Breast1
4CompletedTreatmentAnemias / Graft Versus Host Disease (GVHD) / Leukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes1
4RecruitingTreatmentCentral Nervous System Embryonal Tumors / Medulloblastomas1
Not AvailableActive Not RecruitingTreatmentMalignant Lymphomas1
Not AvailableActive Not RecruitingTreatmentMedulloblastomas / Pinealoblastoma / Supratentorial Embryonal Tumor, Not Otherwise Specified / Untreated Childhood Medulloblastoma / Untreated Childhood Pineoblastoma / Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor1
Not AvailableCompletedTreatmentAdult Acute Lymphoblastic Leukemia in Remission / Adult Acute Myeloid Leukemia in Remission / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Adult Acute Myeloid Leukemia With T(16;16)(p13;q22) / Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) / Adult Nasal Type Extranodal NK/T-Cell Lymphoma / Childhood Acute Lymphoblastic Leukemia in Remission / Childhood Acute Myeloid Leukemia in Remission / Childhood Burkitt Lymphoma / Childhood Diffuse Large Cell Lymphoma / Childhood Immunoblastic Large Cell Lymphoma / Childhood Nasal Type Extranodal NK/T-cell Lymphoma / Chronic Lymphocytic Leukemia (CLL) - Refractory / Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET) / Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Hepatosplenic T-Cell Lymphoma / Intraocular Lymphoma / Nodal marginal zone B-cell lymphomas / Peripheral T-Cell Lymphoma (PTCL) / Plasma Cell Neoplasms / Primary Systemic Amyloidosis / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Acute Myeloid Leukemia / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Hodgkin's Lymphoma / Recurrent Adult Immunoblastic Large Cell Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Myeloid Leukemia / Recurrent Childhood Anaplastic Large Cell Lymphoma / Recurrent Childhood Grade III Lymphomatoid Granulomatosis / Recurrent Childhood Large Cell Lymphoma / Recurrent Childhood Lymphoblastic Lymphoma / Recurrent Childhood Small Noncleaved Cell Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Malignant Testicular Germ Cell Tumor / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Neuroblastoma / Recurrent Small Lymphocytic Lymphoma / Recurrent/Refractory Childhood Hodgkin Lymphoma / Refractory Multiple Myeloma / Regional Neuroblastoma / Splenic Marginal Zone Lymphoma / Testicular Lymphoma / Unspecified Adult Solid Tumor, Protocol Specific / Unspecified Childhood Solid Tumor, Protocol Specific / Waldenström's Macroglobulinemia (WM)1
Not AvailableCompletedTreatmentBrain and Central Nervous System Tumors1
Not AvailableRecruitingTreatmentAtypical Teratoid/Rhabdoid Tumor (AT/RT) / CNS Tumors / Ewing's Family Tumors / Germ Cell Tumors / Hepatoblastomas / Medulloblastomas / Primary Malignant Brain Neoplasms / Renal Tumors / Retinoblastoma / Rhabdomyosarcomas / Soft Tissue Sarcoma (STS) / Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET)1
Not AvailableRecruitingTreatmentMalignancies, Hematologic1
Not AvailableTerminatedTreatmentChronic Leukemias / Leukemia, Acute / Myelodysplastic Syndrome / Non-Hodgkin's Lymphoma (NHL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • APP Pharmaceuticals
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Sicor Pharmaceuticals
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntracavitary; Intravenous; Intravesical100 mg/1
Injection, powder, for solutionIntracavitary; Intravenous; Intravesical15 mg/1
Powder, for solutionIntravenous100 mg
Powder, for solutionIntravenous15 mg
Powder, for solutionOral; Rectal; Vaginal15 mg
Injection, powder, lyophilized, for solutionIntracavitary; Intravenous; Intravesical15 mg/1
Injection, powder, lyophilized, for solutionIntracavitary; Intravenous; Intravesical15 mg/1.5mL
Powder, for solutionIntracavitary; Intravenous; Intravesical15 mg
Prices
Unit descriptionCostUnit
Thiotepa 30 mg vial285.0USD vial
Thiotepa 15 mg vial69.6USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)51.5 °CPhysProp
water solubility1.9E+005 mg/L (at 25 °C)MERCK INDEX (1996)
logP0.53HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility9.27 mg/mLALOGPS
logP0.17ALOGPS
logP-1ChemAxon
logS-1.3ALOGPS
pKa (Strongest Basic)-0.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area9.03 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity50.72 m3·mol-1ChemAxon
Polarizability18.23 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8788
Blood Brain Barrier+0.9823
Caco-2 permeable-0.5097
P-glycoprotein substrateNon-substrate0.7362
P-glycoprotein inhibitor INon-inhibitor0.8096
P-glycoprotein inhibitor IINon-inhibitor0.9946
Renal organic cation transporterNon-inhibitor0.7874
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7558
CYP450 1A2 substrateNon-inhibitor0.6474
CYP450 2C9 inhibitorNon-inhibitor0.7225
CYP450 2D6 inhibitorNon-inhibitor0.8794
CYP450 2C19 inhibitorNon-inhibitor0.593
CYP450 3A4 inhibitorNon-inhibitor0.8618
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7358
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.8992
BiodegradationNot ready biodegradable0.8949
Rat acute toxicity3.8842 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7707
hERG inhibition (predictor II)Non-inhibitor0.866
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-00kn-6900000000-6d6b7c109663ea65ad79
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udj-2910000000-ba7d9f76d09c90907cd5

Taxonomy

Description
This compound 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
Aziridines / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Hydrocarbon derivatives
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)

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
Yes
Actions
Cross-linking/alkylation
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
  1. 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. [PubMed:20459744]
  2. 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. [PubMed:20454509]
  3. 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. [PubMed:21160603]
  4. 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. [PubMed:10913381]

Enzymes

Details
1. Cytochrome P450 2B6
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on September 07, 2007 14:54 / Updated on November 17, 2018 07:20