Compounds > 4-hydroxyifosfamide
Page last updated: 2024-11-07

4-hydroxyifosfamide

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Cross-References

ID SourceID
PubMed CID308171
CHEMBL ID733
CHEBI ID80560
SCHEMBL ID10413711
MeSH IDM0118849

Synonyms (20)

Synonym
4-hydroxyifosfamide
50892-10-9
nsc-208841
nsc208841
2h-1,2-oxazaphosphorine-2-amine, n(2),n(3)-bis(2-chloro- ethyl)tetrahydro-4-hydroxy-, 2-oxide
CHEMBL733
chebi:80560 ,
2h-1,3,2-oxazaphosphorin-4-ol, 3-(2-chloroethyl)-2-((2-chloroethyl)amino)tetrahydro-, 2-oxide
3-(2-chloroethyl)-2-(2-chloroethylamino)-hydroxy-tetrahydro-2h-1,3,2-oxazaphosphorin-2-oxide
JHUJMHKRHQPBRG-UHFFFAOYSA-N
3-(2-chloroethyl)-2-(2-chloroethylamino)-hydroxy-tetrahydro-2h-1,3,2-oxazaphosphorin-2oxide
SCHEMBL10413711
arx5aj985i ,
asta-6569
unii-arx5aj985i
4-hydroxyisophosphamide
DTXSID90308749
Q27149604
3-(2-chloroethyl)-2-((2-chloroethyl)amino)-4-hydroxy-1,3,2-oxazaphosphinane 2-oxide
3-(2-chloroethyl)-2-((2-chloroethyl)amino)-4-hydroxy-1,3,2-oxazaphosphinane2-oxide

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" Independent of the route of ifosfamide application on day 1, the terminal half-life on day 3 (when the drug was given by the alternative route) was decreased in 6 out of the 12 patients, thus indicating self-induction of hepatic metabolism."( Metabolism and pharmacokinetics of oral and intravenous ifosfamide.
Cerny, T; Küpfer, A; Kurowski, V; Wagner, T, 1991)		0.28
" As compared with the values obtained on day 1, on day 5 the terminal half-life and AUC values determined for IF were reduced by 30% (6."( Comparative pharmacokinetics of ifosfamide, 4-hydroxyifosfamide, chloroacetaldehyde, and 2- and 3-dechloroethylifosfamide in patients on fractionated intravenous ifosfamide therapy.
Kurowski, V; Wagner, T, 1993)		0.29
" The population pharmacokinetic model was built in a sequential manner, starting with a covariate-free model and progressing to a covariate model with the aid of generalised additive modelling."( Population pharmacokinetics and exploratory pharmacodynamics of ifosfamide and metabolites after a 72-h continuous infusion in patients with soft tissue sarcoma.
Beijnen, JH; Keizer, HJ; Kerbusch, T; Mathĵt, RA; Ouwerkerk, J; Rodenhuis, S; Schellens, JH, 2001)		0.31
" Autoinduction, dependent on ifosfamide levels, was characterised by an induction half-life of 11."( Population pharmacokinetics and exploratory pharmacodynamics of ifosfamide and metabolites after a 72-h continuous infusion in patients with soft tissue sarcoma.
Beijnen, JH; Keizer, HJ; Kerbusch, T; Mathĵt, RA; Ouwerkerk, J; Rodenhuis, S; Schellens, JH, 2001)		0.31
" This method was applied to a comparative pharmacokinetic study of 4-OHIFO from IFO and three derivatives RXIFO in mice."( Simultaneous quantification of preactivated ifosfamide derivatives and of 4-hydroxyifosfamide by high performance liquid chromatography-tandem mass spectrometry in mouse plasma and its application to a pharmacokinetic study.
Chapuis, H; Couvreur, P; Daudigeos-Dubus, E; Deroussent, A; Desmaële, D; Durand, S; Le Dret, L; Maury, A; Paci, A; Skarbek, C, 2015)		0.42

Dosage Studied

ExcerptRelevanceReference
"13 following systemic dosing of CP and IF, respectively."( Cerebrospinal fluid penetration of active metabolites of cyclophosphamide and ifosfamide in rhesus monkeys.
Arndt, CA; Balis, FM; Colvin, OM; McCully, CL; Poplack, DG, 1988)		0.27
" Similar dose-response curves were found for both metabolites."( Ifosfamide cytotoxicity on human tumor and renal cells: role of chloroacetaldehyde in comparison to 4-hydroxyifosfamide.
Brüggemann, SK; Kisro, J; Wagner, T, 1997)		0.3
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
ifosfamidesCompounds containing an ifosfamide skeleton.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (2)

PathwayProteinsCompounds
Ifosfamide Action Pathway821
Ifosfamide Metabolism Pathway821

Bioassays (5)

Assay IDTitleYearJournalArticle
AID15854Average half life period was determined1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
31P NMR studies of the kinetics of bisalkylation by isophosphoramide mustard: comparisons with phosphoramide mustard.
AID96366In vitro cytotoxicity tested as inhibitory concentration against carcinoma KB cell line2001Bioorganic & medicinal chemistry letters, May-21, Volume: 11, Issue:10
Anodic oxidation of ifosfamide and cyclophosphamide: a biomimetic metabolism model of the oxazaphosphorinane anticancer drugs.
AID7578Active metabolite of ifosfamide determined in humans; A-Active1983Journal of medicinal chemistry, May, Volume: 26, Issue:5
Stereospecific synthesis of chiral metabolites of ifosfamide and their determination in the urine.
AID7584Metabolite of ifosfamide determined in urine; NF-Not found1983Journal of medicinal chemistry, May, Volume: 26, Issue:5
Stereospecific synthesis of chiral metabolites of ifosfamide and their determination in the urine.
AID19113Half life period was determined1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
31P NMR studies of the kinetics of bisalkylation by isophosphoramide mustard: comparisons with phosphoramide mustard.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (23)

TimeframeStudies, This Drug (%)All Drugs %
pre-19905 (21.74)18.7374
1990's10 (43.48)18.2507
2000's4 (17.39)29.6817
2010's4 (17.39)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials5 (18.52%)5.53%
Reviews1 (3.70%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other21 (77.78%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
chloroacetaldehyde
[no description available]		4.2941organochlorine compound
acetaldehyde
Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis.. acetaldehyde : The aldehyde formed from acetic acid by reduction of the carboxy group. It is the most abundant carcinogen in tobacco smoke.. aldehyde : A compound RC(=O)H, in which a carbonyl group is bonded to one hydrogen atom and to one R group.. acetyl group : A group, formally derived from acetic acid by dehydroxylation, which is fundamental to the biochemistry of all forms of life. When bound to coenzyme A, it is central to the metabolism of carbohydrates and fats.		4.2941aldehydecarcinogenic agent;
EC 3.5.1.4 (amidase) inhibitor;
electron acceptor;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
mutagen;
oxidising agent;
Saccharomyces cerevisiae metabolite;
teratogenic agent
niacinamide
nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.		3.4811pyridine alkaloid;
pyridinecarboxamide;
vitamin B3		anti-inflammatory agent;
antioxidant;
cofactor;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Escherichia coli metabolite;
geroprotector;
human urinary metabolite;
metabolite;
mouse metabolite;
neuroprotective agent;
Saccharomyces cerevisiae metabolite;
Sir2 inhibitor
ifosfamide
[no description available]		7.16215ifosfamidesalkylating agent;
antineoplastic agent;
environmental contaminant;
immunosuppressive agent;
xenobiotic
carbamylhydrazine
carbamylhydrazine: RN given refers to parent cpd		1.9910carbohydrazide;
monocarboxylic acid amide;
one-carbon compound;
ureas
acetonitrile
acetonitrile: RN given refers to unlabeled cpd. acetonitrile : A nitrile that is hydrogen cyanide in which the hydrogen has been replaced by a methyl group.		1.9910aliphatic nitrile;
volatile organic compound		EC 3.5.1.4 (amidase) inhibitor;
NMR chemical shift reference compound;
polar aprotic solvent
acrolein
[no description available]		1.9610enalherbicide;
human xenobiotic metabolite;
toxin
methionine sulfoximine
methionine sulfoximine : A non-proteinogenic alpha-amino acid that is the sulfoximine derivative of methionine .		1.9810methionine derivative;
non-proteinogenic alpha-amino acid;
sulfoximide
buthionine sulfoximine
Buthionine Sulfoximine: A synthetic amino acid that depletes glutathione by irreversibly inhibiting gamma-glutamylcysteine synthetase. Inhibition of this enzyme is a critical step in glutathione biosynthesis. It has been shown to inhibit the proliferative response in human T-lymphocytes and inhibit macrophage activation. (J Biol Chem 1995;270(33):1945-7). 2-amino-4-(S-butylsulfonimidoyl)butanoic acid : A non-proteinogenic alpha-amino acid that is homocysteine in which the thiol group carries an oxo, imino and butyl groups.. S-butyl-DL-homocysteine (S,R)-sulfoximine : A sulfoximide that is the sulfoximine derivative of an analogue of DL-methionine in which the S-methyl group is replaced by S-butyl.		1.9810diastereoisomeric mixture;
homocysteines;
non-proteinogenic alpha-amino acid;
sulfoximide		EC 6.3.2.2 (glutamate--cysteine ligase) inhibitor;
ferroptosis inducer
2,2'-dithiodiethanesulfonic acid
[no description available]		3.3811
phosphoramide mustard
[no description available]		1.9710nitrogen mustard;
phosphorodiamide
4-hydroxycyclophosphamide
4-hydroxycyclophosphamide: primary activation metabolite of cyclophosphamide; RN given refers to cpd without isomeric designation. 4-hydroxycyclophosphamide : A phosphorodiamide that consists of 2-amino-1,3,2-oxazaphosphinan-4-ol 2-oxide having two 2-chloroethyl groups attached to the exocyclic nitrogen.		2.940nitrogen mustard;
organochlorine compound;
phosphorodiamide		alkylating agent;
metabolite
isophosphamide mustard
isophosphamide mustard: antitumor metabolite of ifosfamide; palifosfamide-tris is a salt with tris; structure in first source		2.6830phosphorodiamide
dechloroethylcyclophosphamide
dechloroethylcyclophosphamide: structure given in first source; RN given refers to parent cpd		4.8442phosphorodiamide
dechloroethylifosfamide
dechloroethylifosfamide: RN given refers to parent cpd		4.8442organonitrogen heterocyclic compound;
organophosphorus compound
carboxyifosfamide
carboxyifosfamide: structure given in first source		1.9610phosphorodiamide
methotrexate
[no description available]		210dicarboxylic acid;
monocarboxylic acid amide;
pteridines		abortifacient;
antimetabolite;
antineoplastic agent;
antirheumatic drug;
dermatologic drug;
DNA synthesis inhibitor;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
immunosuppressive agent
sorafenib
[no description available]		3.4811(trifluoromethyl)benzenes;
aromatic ether;
monochlorobenzenes;
phenylureas;
pyridinecarboxamide		angiogenesis inhibitor;
anticoronaviral agent;
antineoplastic agent;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
ferroptosis inducer;
tyrosine kinase inhibitor
mesna
Mesna: A sulfhydryl compound used to prevent urothelial toxicity by inactivating metabolites from ANTINEOPLASTIC AGENTS, such as IFOSFAMIDE or CYCLOPHOSPHAMIDE.		8.7821organosulfonic acid
ConditionIndicatedRelationship StrengthStudiesTrials
Sarcoma, Epithelioid
[description not available]		04.3922
Sarcoma
A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant.		04.3922
Sensitivity and Specificity
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)		02.9340
Central Nervous System Neoplasm
[description not available]		03.4511
Central Nervous System Neoplasms
Benign and malignant neoplastic processes that arise from or secondarily involve the brain, spinal cord, or meninges.		03.4511
Carcinoma, Bronchial
[description not available]		03.7821
Cancer of Lung
[description not available]		04.0731
Carcinoma, Bronchogenic
Malignant neoplasm arising from the epithelium of the BRONCHI. It represents a large group of epithelial lung malignancies which can be divided into two clinical groups: SMALL CELL LUNG CANCER and NON-SMALL-CELL LUNG CARCINOMA.		03.7821
Lung Neoplasms
Tumors or cancer of the LUNG.		04.0731
Carcinoma, Oat Cell
[description not available]		03.3811
Carcinoma, Non-Small Cell Lung
[description not available]		03.7821
Carcinoma, Non-Small-Cell Lung
A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.		03.7821
Carcinoma, Small Cell
An anaplastic, highly malignant, and usually bronchogenic carcinoma composed of small ovoid cells with scanty neoplasm. It is characterized by a dominant, deeply basophilic nucleus, and absent or indistinct nucleoli. (From Stedman, 25th ed; Holland et al., Cancer Medicine, 3d ed, p1286-7)		03.3811
Benign Cerebellar Neoplasms
[description not available]		01.9910
Arachnoidal Cerebellar Sarcoma, Circumscribed
[description not available]		01.9910
Medulloblastoma
A malignant neoplasm that may be classified either as a glioma or as a primitive neuroectodermal tumor of childhood (see NEUROECTODERMAL TUMOR, PRIMITIVE). The tumor occurs most frequently in the first decade of life with the most typical location being the cerebellar vermis. Histologic features include a high degree of cellularity, frequent mitotic figures, and a tendency for the cells to organize into sheets or form rosettes. Medulloblastoma have a high propensity to spread throughout the craniospinal intradural axis. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2060-1)		01.9910
Bladder Cancer
[description not available]		0210
Adenocarcinoma Of Kidney
[description not available]		0210
Cancer of Kidney
[description not available]		0210
Urinary Bladder Neoplasms
Tumors or cancer of the URINARY BLADDER.		0210
Carcinoma, Renal Cell
A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.		0210
Carcinoma, Transitional Cell
A malignant neoplasm derived from TRANSITIONAL EPITHELIAL CELLS, occurring chiefly in the URINARY BLADDER; URETERS; or RENAL PELVIS.		0210
Kidney Neoplasms
Tumors or cancers of the KIDNEY.		0210
Carcinoma, Ductal, Breast
An invasive (infiltrating) CARCINOMA of the mammary ductal system (MAMMARY GLANDS) in the human BREAST.		0210
Breast Cancer
[description not available]		0210
Breast Neoplasms
Tumors or cancer of the human BREAST.		0210
Benign Neoplasms
[description not available]		03.3611
Neoplasms
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.		03.3611