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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

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

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
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

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
Substance Class Chemical
Created
by admin
on Fri Dec 15 17:56:34 GMT 2023
Edited
by admin
on Fri Dec 15 17:56:34 GMT 2023
Record UNII
L693H6MM64
Record Status Validated (UNII)
Record Version
  • Download
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
Related Record Type Details
ANHYDROUS->SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY