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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
[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
Amifostine does not inhibit the toxic effects of anthracycline derivates or mitoxantrone on MDR tumor cell lines.
2001 Aug
Assessment of amifostine as protection from chemotherapy-induced toxicities after conventional-dose and high-dose chemotherapy in patients with germ cell tumor.
2001 Aug
[Renal protection with amifostine during intraoperative peritoneal chemohyperthermia (IPCH) with cisplatin (CDDP) for peritoneal carcinosis. Phase 1 study].
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
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
Management of high-risk myelodysplastic syndromes.
2001 Dec
Amifostine does not protect malignant lymphoma cell lines from the cytotoxic effects of various chemotherapeutics in vitro.
2001 Jul
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
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
Radiation therapy and concurrent fixed dose amifostine with escalating doses of twice-weekly gemcitabine in advanced pancreatic cancer.
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
Sensitizers and protectors of radiation and chemotherapy.
2001 Nov-Dec
The role of amifostine as a radioprotector.
2001 Oct
High-dose treatment with (186)Re-HEDP or (153)Sm-EDTMP combined with amifostine in a rabbit model.
2001 Oct
Protective effects of amifostine and its analogues on sulfur mustard toxicity in vitro and in vivo.
2001 Oct 1
Has the outlook improved for amifostine as a clinical radioprotector.
2001 Sep
Poor prognosis acute myelogenous leukemia: 3--biological and molecular biological changes during remission induction therapy.
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
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
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
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
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
Radiotherapy or chemotherapy followed by radiotherapy with or without amifostine in locally advanced lung cancer.
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
Exploring the role of the radioprotector amifostine in locally advanced non-small cell lung cancer: Radiation Therapy Oncology Group trial 98-01.
2002 Jan
Phase II: trial of twice weekly amifostine in patients with non-small cell lung cancer treated with chemoradiotherapy.
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
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
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