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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
Structure of AMIFOSTINE MONOHYDRATE

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

HIDE SMILES / InChI

Description
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

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

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
ETHYOL

Approved Use

Amifostine 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 Date

1995
Secondary
ETHYOL

Approved Use

Amifostine 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 Date

1995
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8 min
910 mg/m² 1 times / day other, intravenous
dose: 910 mg/m²
route of administration: Intravenous
experiment type: OTHER
co-administered:
AMIFOSTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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%)
Nausea and vomiting (all grades, 53%)
Hypotension (grade 3-4, 3%)
Hypotension (all grades, 15%)
Sources: Page: 9
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%)
Nausea and vomiting (all grades, 96%)
Hypotension (grade 3-4, 8%)
Hypotension (all grades, 61%)
Sources: Page: 9
AEs

AEs

AESignificanceDosePopulation
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
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Amifostine inhibits hematopoietic progenitor cell apoptosis by activating NF-kappaB/Rel transcription factors.
1999 Dec 15
Comparison of the protective effects of amifostine and dexrazoxane against the toxicity of doxorubicin in spontaneously hypertensive rats.
2000
Systemic inflammatory response syndrome associated with amifostine.
2000 Apr
Pilot trial of cytoprotection with amifostine given with high-dose chemotherapy and autologous peripheral blood stem cell transplantation.
2000 Aug
Use of amifostine as a chemoprotectant during high-dose chemotherapy in autologous peripheral blood stem cell transplantation.
2000 Dec
The use of reduced doses of amifostine to ameliorate nephrotoxicity of cisplatin/ifosfamide-based chemotherapy in patients with solid tumors.
2000 Jan
Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone.
2000 Mar 1
Quantitation of interferon regulatory factor transcripts in patients with acute myeloid leukemia.
2001
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
Tolerability of the cytoprotective agent amifostine in elderly patients receiving chemotherapy: a comparative study.
2001 Apr
Phase I trial of a twice-daily regimen of amifostine with ifosfamide, carboplatin, and etoposide chemotherapy in children with refractory carcinoma.
2001 Aug 15
[Recommendations of the Working Group 'Supportive Massnahmen in der Onkologie' concerning the Clinical Use of Cytoprotectives].
2001 Feb
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
Effects of amifostine in a patient with an advanced-stage myelodysplastic syndrome.
2001 Jan
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
Amifostine (WR2721) restores transcriptional activity of specific p53 mutant proteins in a yeast functional assay.
2001 Jun 14
Subcutaneous administration of amifostine: a promising therapeutic option in patients with oxaliplatin-related peripheral sensitive neuropathy.
2001 Mar
Dexrazoxane is a potent and specific inhibitor of anthracycline induced subcutaneous lesions in mice.
2001 Mar
Radiation therapy and concurrent fixed dose amifostine with escalating doses of twice-weekly gemcitabine in advanced pancreatic cancer.
2001 Nov 15
Protective effects of amifostine and its analogues on sulfur mustard toxicity in vitro and in vivo.
2001 Oct 1
Has the outlook improved for amifostine as a clinical radioprotector.
2001 Sep
Poor prognosis acute myelogenous leukemia: 3--biological and molecular biological changes during remission induction therapy.
2001 Sep
Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice.
2002
Relationships between cytoprotection and mutation prevention by WR-1065.
2002 Feb
Intrarectal application of amifostine for the prevention of radiation-induced rectal injury.
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
A prospective, nonrandomized study of the impact of amifostine on subsequent hypothyroidism in irradiated patients with head and neck cancers.
2002 Jan
Amifostine in simultaneous radiochemotherapy of advanced head and neck cancer.
2002 Jan
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

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
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
Name Type Language
AMIFOSTINE MONOHYDRATE
MI  
Common Name English
ETHANETHIOL, 2-((3-AMINOPROPYL)AMINO)-, DIHYDROGEN PHOSPHATE (ESTER), MONOHYDRATE
Common Name English
AMIFOSTINE MONOHYDRATE [MI]
Common Name English
Code System Code Type Description
PUBCHEM
83996
Created by admin on Fri Dec 15 17:56:34 GMT 2023 , Edited by admin on Fri Dec 15 17:56:34 GMT 2023
PRIMARY
MERCK INDEX
m1669
Created by admin on Fri Dec 15 17:56:34 GMT 2023 , Edited by admin on Fri Dec 15 17:56:34 GMT 2023
PRIMARY Merck Index
CAS
63717-27-1
Created by admin on Fri Dec 15 17:56:34 GMT 2023 , Edited by admin on Fri Dec 15 17:56:34 GMT 2023
PRIMARY
EPA CompTox
DTXSID70213140
Created by admin on Fri Dec 15 17:56:34 GMT 2023 , Edited by admin on Fri Dec 15 17:56:34 GMT 2023
PRIMARY
FDA UNII
L693H6MM64
Created by admin on Fri Dec 15 17:56:34 GMT 2023 , Edited by admin on Fri Dec 15 17:56:34 GMT 2023
PRIMARY