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
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 |
Molecular Formula | H2O |
Molecular Weight | 18.0153 |
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 |
---|---|---|---|---|
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 |
|||
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 |
---|---|---|
The potential of amifostine: from cytoprotectant to therapeutic agent. | 1999 Nov |
|
Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone. | 2000 Mar 1 |
|
[Current approaches in prevention and therapy of chemo- and radiotherapy-induced oral mucositis]. | 2001 |
|
Immunocytochemical analysis of apoptotic bone marrow cells after treatment of mice with WR-2721 and chemotherapeutic drugs. | 2001 |
|
Tolerability of the cytoprotective agent amifostine in elderly patients receiving chemotherapy: a comparative study. | 2001 Apr |
|
A randomized phase II study of amifostine used as stem cell protectant in non-hodgkin lymphoma patients receiving cisplatin-based salvage chemotherapy prior to stem cell transplant. | 2001 Dec |
|
PBPC mobilization with paclitaxel, ifosfamide, and G-CSF with or without amifostine: results of a prospective randomized trial. | 2001 Feb |
|
Amifostine in combination with erythropoietin and G-CSF promotes multilineage hematopoiesis in patients with myelodysplastic syndrome. | 2001 Jan |
|
Anticancer drug-induced kidney disorders. | 2001 Jan |
|
Amifostine does not protect malignant lymphoma cell lines from the cytotoxic effects of various chemotherapeutics in vitro. | 2001 Jul |
|
Effects of retinoic acid and amifostine on in vitro growth of normal hemopoietic progenitor cells. | 2001 Mar-Apr |
|
Amifostine (Ethyol) as modulator of hepatic and biliary toxicity from intraarterial hepatic chemoembolization: results of a phase I study. | 2001 Mar-Apr |
|
Sensitizers and protectors of radiation and chemotherapy. | 2001 Nov-Dec |
|
High-dose treatment with (186)Re-HEDP or (153)Sm-EDTMP combined with amifostine in a rabbit model. | 2001 Oct |
|
Amifostine protects against early but not late toxic effects of doxorubicin in infant rats. | 2001 Sep 1 |
|
Effects of amifostine on the proliferation and differentiation of megakaryocytic progenitor cells. | 2002 Feb 15 |
|
Rationale for a phase I/II radiation dose-escalation study with concurrent amifostine (Ethyol) and infusional 5-FU chemotherapy for preoperative treatment of unresectable or locally recurrent rectal carcinoma. | 2002 Jan |
|
Intrarectal application of amifostine for the prevention of radiation-induced rectal injury. | 2002 Jan |
|
The potential role of amifostine in the treatment of carcinoma of the uterine cervix: a review. | 2002 Jan |
|
Esophageal cancer and the esophagus: challenges and potential strategies for selective cytoprotection of the tumor-bearing organ during cancer treatment. | 2002 Jan |
|
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 |
|
Influence of amifostine on the toxicity and pharmacokinetics of docetaxel in metastatic breast cancer patients: a pilot study. | 2002 Jan |
|
Inhibition of spontaneous metastases formation by amifostine. | 2002 Jan 10 |
|
Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer. | 2002 Mar 1 |
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
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 17:56:34 GMT 2023
by
admin
on
Fri Dec 15 17:56:34 GMT 2023
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Record UNII |
L693H6MM64
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Record Status |
Validated (UNII)
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Record Version |
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ANHYDROUS->SOLVATE | |||
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |