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
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
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 |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/?term=17602063
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19010997
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3402 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10628381 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Secondary | ETHYOL Approved UseAmifostine 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 Date1995 |
|||
Secondary | ETHYOL Approved UseAmifostine 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 Date1995 |
Doses
Dose | Population | Adverse 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%) Sources: Page: 9Nausea and vomiting (all grades, 53%) Hypotension (grade 3-4, 3%) Hypotension (all grades, 15%) |
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%) Sources: Page: 9Nausea and vomiting (all grades, 96%) Hypotension (grade 3-4, 8%) Hypotension (all grades, 61%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 |
PubMed
Title | Date | PubMed |
---|---|---|
[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
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19010997
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
Edited
Fri Dec 15 17:56:34 GMT 2023
by
admin
on
Fri Dec 15 17:56:34 GMT 2023
|
Record UNII |
L693H6MM64
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
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 | |||
|
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 | ||
|
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 | |||
|
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 | |||
|
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 |