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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

Molecular Formula C5H15N2O3PS
Molecular Weight 214.223
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
ETHYOL
Secondary
ETHYOL

T1/2

ValueDoseCo-administeredAnalytePopulation
8 min
910 mg/m² 1 times / day other, intravenous
AMIFOSTINE plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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
Record UNII
ILA426L95O
Record Status Validated (UNII)
Record Version