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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
Bleomycin genotoxicity and amifostine (WR-2721) cell protection in normal leukocytes vs. K562 tumoral cells.
2002-03-01
Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer.
2002-03-01
Combined therapy with amifostine plus erythropoietin for the treatment of myelodysplastic syndromes.
2002-03
Flow cytometric estimation of the plasma membrane diversity of bone marrow cells in mice treated with WR-2721 and cyclophosphamide.
2002-02-28
Effects of amifostine on the proliferation and differentiation of megakaryocytic progenitor cells.
2002-02-15
Enhancement of fotemustine (Muphoran) cytotoxicity by amifostine in malignant melanoma cell lines.
2002-02
Relationships between cytoprotection and mutation prevention by WR-1065.
2002-02
New dosing regimens for amifostine: a pilot study to compare the relative bioavailability of oral and subcutaneous administration with intravenous infusion.
2002-02
Inhibition of spontaneous metastases formation by amifostine.
2002-01-10
Hypofractionated and accelerated radiotherapy with cytoprotection (HypoARC): a short, safe, and effective postoperative regimen for high-risk breast cancer patients.
2002-01-01
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.
2002-01
Intrarectal application of amifostine for the prevention of radiation-induced rectal injury.
2002-01
The potential role of amifostine in the treatment of carcinoma of the uterine cervix: a review.
2002-01
Esophageal cancer and the esophagus: challenges and potential strategies for selective cytoprotection of the tumor-bearing organ during cancer treatment.
2002-01
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.
2002-01
Radiotherapy or chemotherapy followed by radiotherapy with or without amifostine in locally advanced lung cancer.
2002-01
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.
2002-01
Exploring the role of the radioprotector amifostine in locally advanced non-small cell lung cancer: Radiation Therapy Oncology Group trial 98-01.
2002-01
Phase II: trial of twice weekly amifostine in patients with non-small cell lung cancer treated with chemoradiotherapy.
2002-01
Protection of salivary function by intensity-modulated radiation therapy in patients with head and neck cancer.
2002-01
A phase II trial of subcutaneous amifostine and radiation therapy in patients with head and neck cancer.
2002-01
A prospective, nonrandomized study of the impact of amifostine on subsequent hypothyroidism in irradiated patients with head and neck cancers.
2002-01
Amifostine in simultaneous radiochemotherapy of advanced head and neck cancer.
2002-01
Influence of amifostine on the toxicity and pharmacokinetics of docetaxel in metastatic breast cancer patients: a pilot study.
2002-01
Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice.
2002
Radioprotection of head and neck tissue by amifostine.
2002
Sensitizers and protectors of radiation and chemotherapy.
2001-12-12
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.
2001-12
Management of high-risk myelodysplastic syndromes.
2001-12
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.
2001-11-20
A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188).
2001-11-15
Radiation therapy and concurrent fixed dose amifostine with escalating doses of twice-weekly gemcitabine in advanced pancreatic cancer.
2001-11-15
Alteration of radiation-induced hematotoxicity by amifostine.
2001-11-15
Randomized phase III trial of radiation treatment +/- amifostine in patients with advanced-stage lung cancer.
2001-11-15
Blood thiols following amifostine and mesna infusions, a pediatric oncology group study.
2001-11
Protective effects of amifostine and its analogues on sulfur mustard toxicity in vitro and in vivo.
2001-10-01
The role of amifostine as a radioprotector.
2001-10
High-dose treatment with (186)Re-HEDP or (153)Sm-EDTMP combined with amifostine in a rabbit model.
2001-10
Amifostine protects against early but not late toxic effects of doxorubicin in infant rats.
2001-09-01
Has the outlook improved for amifostine as a clinical radioprotector.
2001-09
Poor prognosis acute myelogenous leukemia: 3--biological and molecular biological changes during remission induction therapy.
2001-09
Phase I trial of a twice-daily regimen of amifostine with ifosfamide, carboplatin, and etoposide chemotherapy in children with refractory carcinoma.
2001-08-15
Amifostine does not inhibit the toxic effects of anthracycline derivates or mitoxantrone on MDR tumor cell lines.
2001-08
Assessment of amifostine as protection from chemotherapy-induced toxicities after conventional-dose and high-dose chemotherapy in patients with germ cell tumor.
2001-08
[Renal protection with amifostine during intraoperative peritoneal chemohyperthermia (IPCH) with cisplatin (CDDP) for peritoneal carcinosis. Phase 1 study].
2001-08
Pharmacologic study of paclitaxel administered with or without the cytoprotective agent amifostine, and given as a single agent or in combination with epirubicin and cisplatin in patients with advanced solid tumors.
2001-08
Amifostine does not protect malignant lymphoma cell lines from the cytotoxic effects of various chemotherapeutics in vitro.
2001-07
Prophylactic efficacy of amifostine and its analogues against sulphur mustard toxicity.
2001-06-21
[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
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
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IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC