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Details

Stereochemistry ACHIRAL
Molecular Formula C5H15N2O3PS
Molecular Weight 214.223
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMIFOSTINE ANHYDROUS

SMILES

NCCCNCCSP(O)(O)=O

InChI

InChIKey=JKOQGQFVAUAYPM-UHFFFAOYSA-N
InChI=1S/C5H15N2O3PS/c6-2-1-3-7-4-5-12-11(8,9)10/h7H,1-6H2,(H2,8,9,10)

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 can reduce mucosal damage after high-dose melphalan conditioning for peripheral blood progenitor cellautotransplant: a retrospective study.
2000 Aug
Use of amifostine as a chemoprotectant during high-dose chemotherapy in autologous peripheral blood stem cell transplantation.
2000 Dec
Experimental model of hepatic venoocclusive disease (VOD) caused by dactinomycin--preliminary report about hepatoprotective effect of amifostine.
2000 May-Jun
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
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
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
Tolerability of the cytoprotective agent amifostine in elderly patients receiving chemotherapy: a comparative study.
2001 Apr
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
Amifostine does not inhibit the toxic effects of anthracycline derivates or mitoxantrone on MDR tumor cell lines.
2001 Aug
[Renal protection with amifostine during intraoperative peritoneal chemohyperthermia (IPCH) with cisplatin (CDDP) for peritoneal carcinosis. Phase 1 study].
2001 Aug
Management of high-risk myelodysplastic syndromes.
2001 Dec
[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
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
Effects of amifostine in a patient with an advanced-stage myelodysplastic syndrome.
2001 Jan
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
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
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
Activation of NFkappaB and MnSOD gene expression by free radical scavengers in human microvascular endothelial cells.
2001 Jun 15
Preliminary results of amifostine administration in combination with recombinant human erythropoietin in patients with myelodysplastic syndromes.
2001 Mar
Clarification on the potential of subcutaneous ethyol as a radioprotective agent.
2001 Mar 1
[Development of cancer chemotherapy. Cytoprotective agents].
2001 Mar-Apr
Effects of retinoic acid and amifostine on in vitro growth of normal hemopoietic progenitor cells.
2001 Mar-Apr
Blood thiols following amifostine and mesna infusions, a pediatric oncology group study.
2001 Nov
Radiation therapy and concurrent fixed dose amifostine with escalating doses of twice-weekly gemcitabine in advanced pancreatic cancer.
2001 Nov 15
Randomized phase III trial of radiation treatment +/- amifostine in patients with advanced-stage lung cancer.
2001 Nov 15
The role of amifostine as a radioprotector.
2001 Oct
Radioprotection of head and neck tissue by amifostine.
2002
Enhancement of fotemustine (Muphoran) cytotoxicity by amifostine in malignant melanoma cell lines.
2002 Feb
Relationships between cytoprotection and mutation prevention by WR-1065.
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
The potential role of amifostine in the treatment of carcinoma of the uterine cervix: a review.
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
Protection of salivary function by intensity-modulated radiation therapy in patients with head and neck cancer.
2002 Jan
A phase II trial of subcutaneous amifostine and radiation therapy in patients with head and neck cancer.
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
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
Bleomycin genotoxicity and amifostine (WR-2721) cell protection in normal leukocytes vs. K562 tumoral cells.
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
Name Type Language
AMIFOSTINE ANHYDROUS
Common Name English
S-(2-((3-AMINOPROPYL)AMINO)ETHYL) DIHYDROGEN PHOSPHOROTHIOATE
Systematic Name English
NSC-758236
Code English
Amifostine [WHO-DD]
Common Name English
AMIFOSTINE [JAN]
Common Name English
WR-2721
Code English
PHOSPHOROTHIOIC ACID S-(2-((3-AMINOPROPYL)AMINO)ETHYL) ESTER
Systematic Name English
AMIFOSTINE [MI]
Common Name English
ETHANETHIOL, 2-((3-AMINOPROPYL)AMINO)-, DIHYDROGEN PHOSPHATE (ESTER)
Common Name English
AMIFOSTINE [HSDB]
Common Name English
amifostine [INN]
Common Name English
2-((3-AMINOPROPYL)AMINO)ETHANETHIOL 1-(DIHYDROGEN PHOSPHATE)
Common Name English
YM-08310
Code English
AMINOPROPYLAMINOETHYL THIOPHOSPHATE
Systematic Name English
ETHIOFOS ANHYDROUS
Common Name English
Classification Tree Code System Code
NDF-RT N0000180854
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
NDF-RT N0000000170
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
NCI_THESAURUS C2080
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
Code System Code Type Description
DRUG BANK
DB01143
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
PRIMARY
CAS
20537-88-6
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
PRIMARY
FDA UNII
ILA426L95O
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
PRIMARY
NSC
758236
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
PRIMARY
PUBCHEM
2141
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
PRIMARY
MERCK INDEX
m1669
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
PRIMARY Merck Index
HSDB
7560
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
PRIMARY
NCI_THESAURUS
C66724
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
PRIMARY
RXCUI
1545987
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
PRIMARY RxNorm
SMS_ID
100000077704
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
PRIMARY
EVMPD
SUB12846MIG
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
PRIMARY
EPA CompTox
DTXSID8022585
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
PRIMARY
DAILYMED
ILA426L95O
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
PRIMARY
INN
4941
Created by admin on Fri Dec 15 15:45:18 GMT 2023 , Edited by admin on Fri Dec 15 15:45:18 GMT 2023
PRIMARY