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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
Evaluation of uroprotective efficacy of amifostine against cyclophosphamide induced hemorrhagic cystitis.
1999 Mar
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
Amifostine plus cisplatin plus vinorelbine in the treatment of advanced non small cell lung cancer: a multicenter phase II study.
2000 Jun
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
WR-2721 reduces intestinal toxicity from concurrent gemcitabine and radiation treatment.
2001
High remission rate in acute myeloblastic leukemia with only two days of chemotherapy.
2001 Apr
[Comments on five clinical trials concerning radiotherapy-induced mucositis in patients with head and neck neoplasms].
2001 Apr
Amifostine does not inhibit the toxic effects of anthracycline derivates or mitoxantrone on MDR tumor cell lines.
2001 Aug
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 Aug
Human kidney tubules detoxify chloroacetaldehyde, a presumed nephrotoxic metabolite of ifosfamide.
2001 Aug
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
Amifostine alone and in combination with erythropoietin for the treatment of favorable myelodysplastic syndrome.
2001 Feb
Preclinical and clinical aspects on the use of amifostine as chemoprotector in neuroblastoma patients.
2001 Jan
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
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
Amifostine does not protect malignant lymphoma cell lines from the cytotoxic effects of various chemotherapeutics in vitro.
2001 Jul
Binding of the aminothiol WR-1065 to transcription factors influences cellular response to anticancer drugs.
2001 Jun
Selective radioprotection of hepatocytes by systemic and portal vein infusions of amifostine in a rat liver tumor model.
2001 Jun 1
Prophylactic efficacy of amifostine and its analogues against sulphur mustard toxicity.
2001 Jun 21
Blood thiols following amifostine and mesna infusions, a pediatric oncology group study.
2001 Nov
A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188).
2001 Nov 15
Alteration of radiation-induced hematotoxicity by amifostine.
2001 Nov 15
Randomized phase III trial of radiation treatment +/- amifostine in patients with advanced-stage lung cancer.
2001 Nov 15
Has the outlook improved for amifostine as a clinical radioprotector.
2001 Sep
Amifostine protects against early but not late toxic effects of doxorubicin in infant rats.
2001 Sep 1
Differential antigenotoxic and cytoprotective effect of amifostine in idarubicin-treated mice.
2002
Radioprotection of head and neck tissue by amifostine.
2002
Enhancement of fotemustine (Muphoran) cytotoxicity by amifostine in malignant melanoma cell lines.
2002 Feb
Flow cytometric estimation of the plasma membrane diversity of bone marrow cells in mice treated with WR-2721 and cyclophosphamide.
2002 Feb 28
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
Radiotherapy or chemotherapy followed by radiotherapy with or without amifostine in locally advanced lung 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
Hypofractionated and accelerated radiotherapy with cytoprotection (HypoARC): a short, safe, and effective postoperative regimen for high-risk breast cancer patients.
2002 Jan 1
Bleomycin genotoxicity and amifostine (WR-2721) cell protection in normal leukocytes vs. K562 tumoral cells.
2002 Mar 1
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