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Details

Stereochemistry ACHIRAL
Molecular Formula C5H15N2O3PS.3H2O
Molecular Weight 268.269
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMIFOSTINE

SMILES

O.O.O.NCCCNCCSP(O)(O)=O

InChI

InChIKey=TXQPXJKRNHJWAX-UHFFFAOYSA-N
InChI=1S/C5H15N2O3PS.3H2O/c6-2-1-3-7-4-5-12-11(8,9)10;;;/h7H,1-6H2,(H2,8,9,10);3*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
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%)
Nausea and vomiting (all grades, 53%)
Hypotension (grade 3-4, 3%)
Hypotension (all grades, 15%)
Sources:
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%)
Nausea and vomiting (all grades, 96%)
Hypotension (grade 3-4, 8%)
Hypotension (all grades, 61%)
Sources:
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
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:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
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
Amifostine can reduce mucosal damage after high-dose melphalan conditioning for peripheral blood progenitor cellautotransplant: a retrospective study.
2000 Aug
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
Amifostine plus cisplatin plus vinorelbine in the treatment of advanced non small cell lung cancer: a multicenter phase II study.
2000 Jun
Experimental model of hepatic venoocclusive disease (VOD) caused by dactinomycin--preliminary report about hepatoprotective effect of amifostine.
2000 May-Jun
[Current approaches in prevention and therapy of chemo- and radiotherapy-induced oral mucositis].
2001
WR-2721 reduces intestinal toxicity from concurrent gemcitabine and radiation treatment.
2001
Quantitation of interferon regulatory factor transcripts in patients with acute myeloid leukemia.
2001
Economic analysis of amifostine as adjunctive support for patients with advanced head and neck cancer: preliminary results from a randomized phase II clinical trial from Germany.
2001
T-cell apoptosis induced by granulocyte colony-stimulating factor is associated with retinoblastoma protein phosphorylation and reduced expression of cyclin-dependent kinase inhibitors.
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
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
Effect of amifostine on toxicities associated with salvage combination chemotherapy.
2001 Feb
Amifostine alone and in combination with erythropoietin for the treatment of favorable myelodysplastic syndrome.
2001 Feb
Bone marrow stem cell protection from chemotherapy by low--molecular-weight compounds.
2001 Feb
Phase III randomized trial of amifostine as a radioprotector in head and neck cancer.
2001 Feb 15
A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplantation.
2001 Feb 2
Anticancer drug-induced kidney disorders.
2001 Jan
A randomized trial of amifostine as a cytoprotective agent in patients receiving chemotherapy for small cell lung cancer.
2001 Jan 5
Phase I-II study of escalating doses of amifostine combined with high-dose cyclophosphamide.
2001 Jun
Effect of amifostine on lipid peroxidation caused by cisplatin in rat kidney.
2001 Jun
Selective radioprotection of hepatocytes by systemic and portal vein infusions of amifostine in a rat liver tumor model.
2001 Jun 1
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
Clarification on the potential of subcutaneous ethyol as a radioprotective agent.
2001 Mar 1
[Adjuvant chemotherapy of cervix carcinoma--results of a phase II study].
2001 May
A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188).
2001 Nov 15
Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice.
2002
Radioprotection of head and neck tissue by amifostine.
2002
Relationships between cytoprotection and mutation prevention by WR-1065.
2002 Feb
New dosing regimens for amifostine: a pilot study to compare the relative bioavailability of oral and subcutaneous administration with intravenous infusion.
2002 Feb
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
Phase II evaluation of amifostine as an esophageal mucosal protectant in the treatment of limited-stage small cell lung cancer with chemotherapy and twice-daily radiation.
2002 Jan
Phase II: trial of twice weekly amifostine in patients with non-small cell lung cancer treated with chemoradiotherapy.
2002 Jan
Influence of amifostine on the toxicity and pharmacokinetics of docetaxel in metastatic breast cancer patients: a pilot study.
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
Combined therapy with amifostine plus erythropoietin for the treatment of myelodysplastic syndromes.
2002 Mar
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 Mon Mar 31 18:25:30 GMT 2025
Edited
by admin
on Mon Mar 31 18:25:30 GMT 2025
Record UNII
M487QF2F4V
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AMIFOSTINE TRIHYDRATE
MI   WHO-DD  
Preferred Name English
AMIFOSTINE
MART.   ORANGE BOOK   USAN   USP   VANDF  
USAN  
Official Name English
AMIFOSTINE [MART.]
Common Name English
AMIFOSTINE [USP MONOGRAPH]
Common Name English
GAMMAPHOS
Common Name English
Amifostine trihydrate [WHO-DD]
Common Name English
AMIFOSTINE [USP-RS]
Common Name English
WR-2721 TRIHYDRATE
Code English
AMIFOSTINE [USAN]
Common Name English
S-[2-[(3-Aminopropyl)amino]ethyl] dihydrogen phosphorothioate, trihydrate
Systematic Name English
NSC-296961
Code English
AMIFOSTINE [VANDF]
Common Name English
AMIFOSTINE TRIHYDRATE [MI]
Common Name English
ETHYOL
Brand Name English
ETHIOFOS
Common Name English
ETHANETHIOL, 2-((3-AMINOPROPYL)AMINO)-, DIHYDROGEN PHOSPHATE (ESTER), TRIHYDRATE
Common Name English
AMIFOSTINE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 128399
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
FDA ORPHAN DRUG 116298
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
WHO-VATC QV03AF05
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
FDA ORPHAN DRUG 24187
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
FDA ORPHAN DRUG 42989
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
FDA ORPHAN DRUG 111698
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
NDF-RT N0000180854
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
FDA ORPHAN DRUG 42789
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
NCI_THESAURUS C2080
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
FDA ORPHAN DRUG 42889
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
LIVERTOX 36
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
WHO-ATC V03AF05
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
Code System Code Type Description
MESH
D004999
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
USAN
DD-7
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
DRUG BANK
DB01143
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
RXCUI
4126
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY RxNorm
DAILYMED
M487QF2F4V
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
WIKIPEDIA
AMIFOSTINE
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
RS_ITEM_NUM
1019406
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
MERCK INDEX
m1669
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY Merck Index
SMS_ID
100000091456
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
NCI_THESAURUS
C488
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
EPA CompTox
DTXSID40150210
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
EVMPD
SUB27016
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
CHEBI
2636
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
FDA UNII
M487QF2F4V
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
ChEMBL
CHEMBL1006
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
CAS
112901-68-5
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
NSC
296961
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
DRUG CENTRAL
156
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
PUBCHEM
148139
Created by admin on Mon Mar 31 18:25:30 GMT 2025 , Edited by admin on Mon Mar 31 18:25:30 GMT 2025
PRIMARY
Related Record Type Details
ANHYDROUS->SOLVATE
PARENT -> SALT/SOLVATE
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC