52-24-4 Usage
Uses
Used in Cancer Treatment:
Triethylenethiophosphoramide is used as a cancer chemotherapeutic and alkylating agent for the treatment of various kinds of cancer, including breast, ovarian, and bladder cancer. It is particularly effective against cancers resistant to chemotherapy due to its antineoplastic properties.
Used in Conditioning Treatment:
Thiotepa is also used as a conditioning treatment prior to hematopoietic progenitor cell transplantation (HPCT) to prepare the patient's body for the transplant.
Used in Suzuki Reaction:
Triethylenethiophosphoramide is utilized in the Suzuki reaction, a type of chemical reaction in organic chemistry.
Used in Antiseborrheic and Antipruritic Applications:
Thiotepa is employed in the treatment of seborrheic dermatitis and pruritus, providing relief from itching and skin irritation.
Used as an Insect Sterilant:
Triethylenethiophosphoramide is also used as an insect sterilant, contributing to pest control efforts.
Originator
Thio-Tepa,Lederle,US,1959
Indications
Although thiotepa is chemically less reactive than the nitrogen
mustards, it is thought to act by similar mechanisms.
Its oral absorption is erratic. After intravenous injection,
the plasma half-life is less than 2 hours. Urinary
excretion accounts for 60 to 80% of eliminated drug.
Thiotepa has antitumor activity against ovarian and
breast cancers and lymphomas. However, it has been
largely supplanted by cyclophosphamide and other nitrogen
mustards for treatment of these diseases. It is
used by direct instillation into the bladder for multifocal
local bladder carcinoma.
Nausea and myelosuppression are the major toxicities
of thiotepa. It is not a local vesicant and has been
safely injected intramuscularly and even intrathecally.
Manufacturing Process
A solution of 30.3 parts of triethylamine and 12.9 parts of ethylenimine in 180
parts of dry benzene is treated with a solution of 16.9 parts of thiophosphoryl
chloride in 90 parts of dry benzene at 5°C to 10°C. Triethylamine
hydrochloride is filtered off. The benzene solvent is distilled from the filtrate
under reduced pressure and the resulting crude product is recrystallized from
petroleum ether. The N,N',N''-triethylenethiophosphoramide had a melting
point of 51.5°C.
Therapeutic Function
Antineoplastic
Air & Water Reactions
Water soluble.
Reactivity Profile
Triethylenethiophosphoramide polymerizes readily upon exposure to heat or moisture, especially at acidic pH.
Hazard
Confirmed carcinogen.
Fire Hazard
Flash point data for Triethylenethiophosphoramide are not available. Triethylenethiophosphoramide is probably combustible.
Biochem/physiol Actions
The unstable nitrogen-carbon groups alkylate with DNA which causes irreversible DNA damage. They stop tumor growth by crosslinking guanine nucleobases in DNA double-helix strands, directly attacking DNA. The DNA strands are unable to uncoil and separate which halts cell division.
Mechanism of action
Thiotepa and the TEPA metabolite readily enter the CNS after systemic administration, leading to dizziness, blurred vision, and headaches. More critically, these agents also are severe myelosuppressants and can induce leukopenia, thrombocytopenia, and anemia. Patients treated with thiotepa are at high risk for infection and hemorrhage.
Clinical Use
This antineoplastic agent is most commonly employed in the treatment of ovarian and breast cancers, as well as papillary carcinoma of the bladder.
Side effects
Patients have died from myelosuppression after intravesically administered thiotepa. The drug also causes damage to the hepatic and renal systems. Dose and/or administration frequency should be increased slowly, even if the initial response to the drug is sluggish, or unacceptable toxicity may result.
Safety Profile
Confirmed human
carcinogen producing leukemia. Poison by
ingestion, intraperitoneal, intravenous, and
subcutaneous routes. Experimental
teratogenic data. Human systemic effects by
parenteral route: paresthesia, bone marrow
changes, and leukemia. Experimental
reproductive effects. Human mutation data
reported. When heated to decomposition it
emits very toxic fumes of POx, SOx, and
NOx.
Synthesis
Thiotepa, tris(1-aziridinyl)phosphine sulfate (30.2.2.1), is made by reacting
ethylenimine with phosphorous sulfochloride .
Potential Exposure
Used in the treatment of cancers resistant to chemotherapy. Antineoplastic: thiotepa has been prescribed for a wide variety of neoplastic diseases: adenocarcinomas of the breast and the ovary; superficial carcinoma of the urinary bladder; controlling intracavitary or localized neoplastic disease; lymphomas, such aslymphosarcomas and Hodgkin’s disease; as well as bronchogenic carcinoma.
Drug interactions
Potentially hazardous interactions with other drugs Antipsychotics: avoid concomitant use with clozapine. Avoid concomitant use with other myelosuppressive agents. Administration
Carcinogenicity
Thiotepa is known to be a human carcinogen based on sufficient evidence from studies in humans. Thiotepa was first listed in the Second Annual Report on Carcinogens in 1981 as reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals and insufficient evidenceof carcinogenicity from studies in humans. Thiotepa was reclassified as known to be a human carcinogen in the Eighth Report on Carcinogens in 1998.
Metabolism
Thiotepa is extensively metabolised to triethylenephosphoramide (TEPA), the primary metabolite, and some of the other metabolites have cytotoxic activity and are eliminated more slowly than the parent compound. It is excreted in the urine: less than 2% of a dose is reported to be present as unchanged drug or its primary metabolite.
Toxicity evaluation
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. This causes DNA cross-linking and prevents the
replication of rapidly dividing cells.
Incompatibilities
Tris(aziridinyl)phosphine sulfide polymerizes readily upon exposure to heat or moisture, especially at acidic pH. Incompatible with strong oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides.
Check Digit Verification of cas no
The CAS Registry Mumber 52-24-4 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 2 respectively; the second part has 2 digits, 2 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 52-24:
(4*5)+(3*2)+(2*2)+(1*4)=34
34 % 10 = 4
So 52-24-4 is a valid CAS Registry Number.
InChI:InChI=1/C6H12N3PS/c11-10(7-1-2-7,8-3-4-8)9-5-6-9/h1-6H2
52-24-4Relevant academic research and scientific papers
Method for preparing thiotepa
-
Paragraph 0031; 0034-0036; 0037; 0040-0042; 0043; 0046-0048, (2018/09/21)
The invention provides a method for preparing thiotepa. The method comprises the following steps: cooling ethylenimine and an organic solvent to a temperature of 15-17 DEG C, dropping an organic solvent of trihalothiophosphorus, dropping an acid-binding agent when the trihalothiophosphorus is dropped to reach a scheduled quantity Y of 49%, maintaining the temperature of 15-17 DEG C, and reacting for 30-45 minutes; filtering, performing reduced pressure distillation on the filtrate to remove the organic solvent so as to obtain the residue, and purifying, so as to obtain the thiotepa. The raw materials and reagent used in the preparation method provided by the invention are cheap and readily available, the produced three wastes are less, and the method is simple in operation, high in yield and suitable for industrial production.
THERAPEUTIC FOR HEPATIC CANCER
-
, (2011/02/18)
A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.
Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
-
, (2010/05/13)
Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.
Particles with improved solubilization capacity
-
, (2008/06/13)
A particle is disclosed that comprises a first volume of hydrophobe-rich material with tunable dissolution and solubilization characteristics and a distinct second volume of nanostructured nonlamellar liquid crystalline material, said second volume containing said first domain and being capable of being in equilibrium with said first volume. Preferably, the nanostructured nonlamellar liquid crystalline material is capable of being in equilibrium with a polar solvent or a water-immiscible solvent or both.
Soluble phosphorylated glucan: methods and compositions for treatment of neoplastic diseases
-
, (2008/06/13)
A new class of soluble phosphorylated glucans is described as well as the process for making the same. According to one embodiment, the soluble phosphorylated glucan is derived from the yeast Saccharomyces cerevisiae. The soluble phosphorylated glucans are useful for prophylactic and therapeutic applications against neoplastic, bacteria, viral, fungal and parasitic diseases. The soluble phosphorylated glucans are used either alone or in combination with a known antimicrobial agent for prophylactic and therapeutic antimicrobial applications. Additionally, they may be administered either alone or as a non-toxic adjuvant, in combination with chemotherapy. The soluble phosphorylated glucans are also useful for stimulating macrophage cells, either in vivo or in vitro, to produce a cytotoxic/cyctostatic factor effective against cancer cells.
Method of treating nausea and vomiting with certain substituted-phenylalkylamino (and aminoacid) derivatives and other serotonin depleting agents
-
, (2008/06/13)
A method for the treatment of emesis in a mammal, which method comprises administering to said mammal an emesis inhibiting amount of a compound which depletes serotonin in the brain of mammals; among which are compounds having the formula: STR1 wherein, R is selected from hydrogen, loweralkyl, trifluoromethyl, carboxyl, or loweralkoxycarbonyl; R1 and R2 are hydrogen or loweralkyl; Z is trifluoromethyl or halogen; the optical isomers and pharmaceutically acceptable salts thereof; two of the preferred compounds of the invention are fenfluramine and norfenfluramine.
Amino acid and hydroxyamino acid transporter compounds for therapeutic applications, process and use
-
, (2008/06/13)
Amino acid and hydroxyamino acid transporter compounds are provided, in which an amino acid or hydroxyamino acid as a carrier is linked via an ester linkage to a therapeutic compound, and having one of the general formulae: in which AA represents the amino acid or hydroxyamino acid, HAA represents the hydroxyamino acid, and Z1 and Z2 represent a therapeutic compound, or a linking compound attached to COOH or OH of the hydroxyamino acid and to the therapeutic compound, as well as a process for preparing the same, and a process for administration of the same to animals, to obtain the benefit of the therapeutic effect of the therapeutic compound.
