Details
Stereochemistry | ACHIRAL |
Molecular Formula | C5H15N2O3PS |
Molecular Weight | 214.223 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NCCCNCCSP(O)(O)=O
InChI
InChIKey=JKOQGQFVAUAYPM-UHFFFAOYSA-N
InChI=1S/C5H15N2O3PS/c6-2-1-3-7-4-5-12-11(8,9)10/h7H,1-6H2,(H2,8,9,10)
Molecular Formula | C5H15N2O3PS |
Molecular Weight | 214.223 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/?term=17602063
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/?term=17602063
Amifostine is an organic thiophosphate cytoprotective agent known chemically as 2-[(3¬ aminopropyl)amino]ethanethiol dihydrogen phosphate (ester), it’s adjuvant used in cancer chemotherapy and radiotherapy involving DNA-binding chemotherapeutic agents. It is marketed under the trade name Ethyol. Amifostine is a prodrug and is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite. This metabolite is believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues. The ability of Ethyol to differentially protect normal tissues is attributed to the higher capillary alkaline phosphatase activity, higher pH and better vascularity of normal tissues relative to tumor tissue, which results in a more rapid generation of the active thiol metabolite as well as a higher rate constant for uptake into cells. The higher concentration of the thiol metabolite in normal tissues is available to bind to, and thereby detoxify, reactive metabolites of cisplatin. This thiol metabolite can also scavenge reactive oxygen species generated by exposure to either cisplatin or radiation. Healthy cells are preferentially protected because amifostine and metabolites are present in healthy cells at 100-fold greater concentrations than in tumor cells.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19010997
Curator's Comment: Because amifostine does not cross the blood–brain barrier, the central nervous system, often the dose-limiting organ in radiotherapy, is not protected
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3402 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10628381 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Secondary | ETHYOL Approved UseAmifostine for Injection is indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer. Amifostine for Injection is indicated to reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands (see Clinical Studies ). For the approved indications, the clinical data do not suggest that the effectiveness of cisplatin based chemotherapy regimens or radiation therapy is altered by Amifostine for Injection. There are at present only limited data on the effects of amifostine on the efficacy of chemotherapy or radiotherapy in other settings. Amifostine should not be administered to patients in other settings where chemotherapy can produce a significant survival benefit or cure, or in patients receiving definitive radiotherapy, except in the context of a clinical study (see WARNINGS). Launch Date1995 |
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Secondary | ETHYOL Approved UseAmifostine for Injection is indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patient s with advanced ovarian cancer. Amifostine for Injection is indicated to reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands (see Clinical Studies ). For the approved indications, the clinical data do not suggest that the effectiveness of cisplatin based chemotherapy regimens or radiation therapy is altered by Amifostine for Injection. There are at present only limited data on the effects of amifostine on the efficacy of chemotherapy or radiotherapy in other settings. Amifostine should not be administered to patients in other settings where chemotherapy can produce a significant survival benefit or cure, or in patients receiving definitive radiotherapy, except in the context of a clinical study (see WARNINGS). Launch Date1995 |
Doses
Dose | Population | Adverse events |
---|---|---|
200 mg/m2 1 times / day multiple, intravenous Recommended Dose: 200 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Other AEs: Nausea and vomiting, Nausea and vomiting... Other AEs: Nausea and vomiting (grade 3-4, 8%) Sources: Nausea and vomiting (all grades, 53%) Hypotension (grade 3-4, 3%) Hypotension (all grades, 15%) |
910 mg/m2 1 times / day multiple, intravenous Recommended Dose: 910 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 910 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Disc. AE: Blood pressure decreased... Other AEs: Nausea and vomiting, Nausea and vomiting... AEs leading to discontinuation/dose reduction: Blood pressure decreased (<3%) Other AEs:Nausea and vomiting (grade 3-4, 30%) Sources: Nausea and vomiting (all grades, 96%) Hypotension (grade 3-4, 8%) Hypotension (all grades, 61%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Hypotension | all grades, 15% | 200 mg/m2 1 times / day multiple, intravenous Recommended Dose: 200 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Nausea and vomiting | all grades, 53% | 200 mg/m2 1 times / day multiple, intravenous Recommended Dose: 200 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Hypotension | grade 3-4, 3% | 200 mg/m2 1 times / day multiple, intravenous Recommended Dose: 200 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Nausea and vomiting | grade 3-4, 8% | 200 mg/m2 1 times / day multiple, intravenous Recommended Dose: 200 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Blood pressure decreased | <3% Disc. AE |
910 mg/m2 1 times / day multiple, intravenous Recommended Dose: 910 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 910 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Hypotension | all grades, 61% | 910 mg/m2 1 times / day multiple, intravenous Recommended Dose: 910 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 910 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Nausea and vomiting | all grades, 96% | 910 mg/m2 1 times / day multiple, intravenous Recommended Dose: 910 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 910 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Nausea and vomiting | grade 3-4, 30% | 910 mg/m2 1 times / day multiple, intravenous Recommended Dose: 910 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 910 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Hypotension | grade 3-4, 8% | 910 mg/m2 1 times / day multiple, intravenous Recommended Dose: 910 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 910 mg/m2, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Sample Use Guides
For Reduction of Cumulative Renal Toxicity with Chemotherapy:
The recommended starting dose is 910 mg/m2 administered once daily as a 15-minute infusion.
For Reduction of Moderate to Severe Xerostomia from Radiation of the Head and Neck:
The recommended dose is 200 mg/m2 administered once daily as a 3-minute infusion starting 15-30 minutes prior to standard fraction radiation therapy (1.8-2.0 Gy).
infusion, starting 30 minutes prior to chemotherapy.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19010997
Human pulmonary EC were grown on golden microelectrodes. Cells were pretreated with WR-1065 (unprotected form of amifostine, used for cell culture treatments) (0.4 mM, 1 mM or 4 mM, 30 min) followed by stimulation with 250 mM H2O2 (Panel A). EC were pretreated with 4 mM
Substance Class |
Chemical
Created
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ILA426L95O
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N0000180854
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N0000000170
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C2080
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Volume of Distribution | PHARMACOKINETIC |
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