Details
Stereochemistry | ACHIRAL |
Molecular Formula | C5H15N2O3PS.H2O |
Molecular Weight | 232.238 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O.NCCCNCCSP(O)(O)=O
InChI
InChIKey=CWHOHHKTRJUFTR-UHFFFAOYSA-N
InChI=1S/C5H15N2O3PS.H2O/c6-2-1-3-7-4-5-12-11(8,9)10;/h7H,1-6H2,(H2,8,9,10);1H2
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 |
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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 Co-administed with:: radiation treatment Sources: Page: 9 |
unhealthy, adult n = 150 Health Status: unhealthy Condition: Head and Neck Cancer Age Group: adult Sex: unknown Population Size: 150 Sources: Page: 9 |
Other AEs: Nausea and vomiting, Nausea and vomiting... Other AEs: Nausea and vomiting (grade 3-4, 8%) Sources: Page: 9Nausea 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 Co-administed with:: cisplatin(100 mg/m2) Sources: Page: 9 |
unhealthy, adult n = 122 Health Status: unhealthy Condition: Ovarian Cancer Age Group: adult Sex: unknown Population Size: 122 Sources: Page: 9 |
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: Page: 9Nausea 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 Co-administed with:: radiation treatment Sources: Page: 9 |
unhealthy, adult n = 150 Health Status: unhealthy Condition: Head and Neck Cancer Age Group: adult Sex: unknown Population Size: 150 Sources: Page: 9 |
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 Co-administed with:: radiation treatment Sources: Page: 9 |
unhealthy, adult n = 150 Health Status: unhealthy Condition: Head and Neck Cancer Age Group: adult Sex: unknown Population Size: 150 Sources: Page: 9 |
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 Co-administed with:: radiation treatment Sources: Page: 9 |
unhealthy, adult n = 150 Health Status: unhealthy Condition: Head and Neck Cancer Age Group: adult Sex: unknown Population Size: 150 Sources: Page: 9 |
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 Co-administed with:: radiation treatment Sources: Page: 9 |
unhealthy, adult n = 150 Health Status: unhealthy Condition: Head and Neck Cancer Age Group: adult Sex: unknown Population Size: 150 Sources: Page: 9 |
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 Co-administed with:: cisplatin(100 mg/m2) Sources: Page: 9 |
unhealthy, adult n = 122 Health Status: unhealthy Condition: Ovarian Cancer Age Group: adult Sex: unknown Population Size: 122 Sources: Page: 9 |
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 Co-administed with:: cisplatin(100 mg/m2) Sources: Page: 9 |
unhealthy, adult n = 122 Health Status: unhealthy Condition: Ovarian Cancer Age Group: adult Sex: unknown Population Size: 122 Sources: Page: 9 |
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 Co-administed with:: cisplatin(100 mg/m2) Sources: Page: 9 |
unhealthy, adult n = 122 Health Status: unhealthy Condition: Ovarian Cancer Age Group: adult Sex: unknown Population Size: 122 Sources: Page: 9 |
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 Co-administed with:: cisplatin(100 mg/m2) Sources: Page: 9 |
unhealthy, adult n = 122 Health Status: unhealthy Condition: Ovarian Cancer Age Group: adult Sex: unknown Population Size: 122 Sources: Page: 9 |
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 Co-administed with:: cisplatin(100 mg/m2) Sources: Page: 9 |
unhealthy, adult n = 122 Health Status: unhealthy Condition: Ovarian Cancer Age Group: adult Sex: unknown Population Size: 122 Sources: Page: 9 |
PubMed
Title | Date | PubMed |
---|---|---|
Amifostine inhibits hematopoietic progenitor cell apoptosis by activating NF-kappaB/Rel transcription factors. | 1999 Dec 15 |
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Comparison of the protective effects of amifostine and dexrazoxane against the toxicity of doxorubicin in spontaneously hypertensive rats. | 2000 |
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Systemic inflammatory response syndrome associated with amifostine. | 2000 Apr |
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Pilot trial of cytoprotection with amifostine given with high-dose chemotherapy and autologous peripheral blood stem cell transplantation. | 2000 Aug |
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Use of amifostine as a chemoprotectant during high-dose chemotherapy in autologous peripheral blood stem cell transplantation. | 2000 Dec |
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The use of reduced doses of amifostine to ameliorate nephrotoxicity of cisplatin/ifosfamide-based chemotherapy in patients with solid tumors. | 2000 Jan |
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Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone. | 2000 Mar 1 |
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Quantitation of interferon regulatory factor transcripts in patients with acute myeloid leukemia. | 2001 |
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Amifostine: an update on its clinical status as a cytoprotectant in patients with cancer receiving chemotherapy or radiotherapy and its potential therapeutic application in myelodysplastic syndrome. | 2001 |
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Tolerability of the cytoprotective agent amifostine in elderly patients receiving chemotherapy: a comparative study. | 2001 Apr |
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Phase I trial of a twice-daily regimen of amifostine with ifosfamide, carboplatin, and etoposide chemotherapy in children with refractory carcinoma. | 2001 Aug 15 |
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[Recommendations of the Working Group 'Supportive Massnahmen in der Onkologie' concerning the Clinical Use of Cytoprotectives]. | 2001 Feb |
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PBPC mobilization with paclitaxel, ifosfamide, and G-CSF with or without amifostine: results of a prospective randomized trial. | 2001 Feb |
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Amifostine in combination with erythropoietin and G-CSF promotes multilineage hematopoiesis in patients with myelodysplastic syndrome. | 2001 Jan |
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Effects of amifostine in a patient with an advanced-stage myelodysplastic syndrome. | 2001 Jan |
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High dose daily amifostine and hypofractionated intensively accelerated radiotherapy for locally advanced breast cancer. A phase I/II study and report on early and late sequellae. | 2001 Jul-Aug |
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Amifostine (WR2721) restores transcriptional activity of specific p53 mutant proteins in a yeast functional assay. | 2001 Jun 14 |
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Subcutaneous administration of amifostine: a promising therapeutic option in patients with oxaliplatin-related peripheral sensitive neuropathy. | 2001 Mar |
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Dexrazoxane is a potent and specific inhibitor of anthracycline induced subcutaneous lesions in mice. | 2001 Mar |
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Radiation therapy and concurrent fixed dose amifostine with escalating doses of twice-weekly gemcitabine in advanced pancreatic cancer. | 2001 Nov 15 |
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Protective effects of amifostine and its analogues on sulfur mustard toxicity in vitro and in vivo. | 2001 Oct 1 |
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Has the outlook improved for amifostine as a clinical radioprotector. | 2001 Sep |
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Poor prognosis acute myelogenous leukemia: 3--biological and molecular biological changes during remission induction therapy. | 2001 Sep |
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Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice. | 2002 |
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Relationships between cytoprotection and mutation prevention by WR-1065. | 2002 Feb |
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Intrarectal application of amifostine for the prevention of radiation-induced rectal injury. | 2002 Jan |
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Randomized phase III study of chemoradiation with or without amifostine for patients with favorable performance status inoperable stage II-III non-small cell lung cancer: preliminary results. | 2002 Jan |
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A prospective, nonrandomized study of the impact of amifostine on subsequent hypothyroidism in irradiated patients with head and neck cancers. | 2002 Jan |
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Amifostine in simultaneous radiochemotherapy of advanced head and neck cancer. | 2002 Jan |
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Hypofractionated and accelerated radiotherapy with cytoprotection (HypoARC): a short, safe, and effective postoperative regimen for high-risk breast cancer patients. | 2002 Jan 1 |
|
Inhibition of spontaneous metastases formation by amifostine. | 2002 Jan 10 |
Patents
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
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83996
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m1669
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63717-27-1
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DTXSID70213140
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L693H6MM64
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ACTIVE MOIETY
SUBSTANCE RECORD