4-HYDROXYIFOSFAMIDE

Details

Stereochemistry	UNKNOWN
Molecular Formula	C7H15Cl2N2O3P
Molecular Weight	277.085
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1CCOP(=O)(NCCCl)N1CCCl

InChI

InChIKey=JHUJMHKRHQPBRG-UHFFFAOYSA-N

InChI=1S/C7H15Cl2N2O3P/c8-2-4-10-15(13)11(5-3-9)7(12)1-6-14-15/h7,12H,1-6H2,(H,10,13)

HIDE SMILES / InChI

Molecular Formula	C7H15Cl2N2O3P
Molecular Weight	277.085
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27413637 | https://www.ncbi.nlm.nih.gov/pubmed/17786181 | https://pubchem.ncbi.nlm.nih.gov/compound/Glufosfamidehttp://www.ncbi.nlm.nih.gov/pubmed/?term=17464949

Ifosfamide (IF) is a widely used antitumor prodrug. It is in the oxazaphosphorine class of alkylating agents, and it is effective against solid tumors. Ifosfamide mechanism of crosslinking DNA plays a major role in preventing cancer cells from proliferating. Ifosfamide is approved by FDA for the treatment of germ cell testicular cancer.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 282 Target ID: CHEMBL2311221 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019763s019lbl.pdf	Crosslinking Agent 83

Conditions

Condition	Modality	Targets	Highest Phase	Product
Germ cell testicular cancer 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019763s019lbl.pdf	Primary		Approved 8583	IFEX Approved Use Ifosfamide injection, used in combination with certain other approved antineoplastic agents, is indicated for third line chemotherapy of germ cell testicular cancer. It should be used in combination with a prophylactic agent for hemorrhagic cystitis, such as mesna. Launch Date 1988

C_max

Value	Dose	Analyte	Population
346 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9528844	3 g/m² single, intravenous dose: 3 g/m² route of administration: Intravenous experiment type: SINGLE co-administered:	IFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
200 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1795004	1.5 g/m² single, oral dose: 1.5 g/m² route of administration: Oral experiment type: SINGLE co-administered:	IFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
203 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1795004	1.5 g/m² single, intravenous dose: 1.5 g/m² route of administration: Intravenous experiment type: SINGLE co-administered:	IFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
2197 mM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9528844	3 g/m² single, intravenous dose: 3 g/m² route of administration: Intravenous experiment type: SINGLE co-administered:	IFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1360 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1795004	1.5 g/m² single, oral dose: 1.5 g/m² route of administration: Oral experiment type: SINGLE co-administered:	IFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1520 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1795004	1.5 g/m² single, intravenous dose: 1.5 g/m² route of administration: Intravenous experiment type: SINGLE co-administered:	IFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
7.54 mM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8339288	3 g/m² 1 times / day multiple, intravenous dose: 3 g/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	IFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
4.33 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9528844	3 g/m² single, intravenous dose: 3 g/m² route of administration: Intravenous experiment type: SINGLE co-administered:	IFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1795004	1.5 g/m² single, oral dose: 1.5 g/m² route of administration: Oral experiment type: SINGLE co-administered:	IFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/1795004	1.5 g/m² single, intravenous dose: 1.5 g/m² route of administration: Intravenous experiment type: SINGLE co-administered:	IFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.12 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8339288	3 g/m² 1 times / day multiple, intravenous dose: 3 g/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	IFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
100% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019763s017lbl.pdf	unknown		IFOSFAMIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
18 g/m2 1 times / day multiple, intravenous MTD Dose: 18 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 18 g/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10572607	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10572607	DLT: Neutropenia, Infection... Dose limiting toxicities: Neutropenia (grade 4, 83.3%) Infection (severe, 33.3%) Thrombocytopenia (grade 4, 66.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/10572607
2.25 g/m2 1 times / day multiple, intravenous MTD Dose: 2.25 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 2.25 g/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11840607	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/11840607	DLT: Neutropenia, Febrile neutropenia... Dose limiting toxicities: Neutropenia (grade 4, 66.7%) Febrile neutropenia (grade 5, 33.3%) Thrombocytopenia (grade 4, 66.7%) Anemia (grade 4, 66.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/11840607
1.2 g/m2 1 times / day multiple, intravenous Recommended Dose: 1.2 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 1.2 g/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019763s017lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019763s017lbl.pdf	Disc. AE: Nephrotoxicity, Renal failure... AEs leading to discontinuation/dose reduction: Nephrotoxicity (severe) Renal failure (severe) Cystitis hemorrhagic (severe) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019763s017lbl.pdf

AEs

AE	Significance	Dose	Population
Thrombocytopenia	grade 4, 66.7% DLT	18 g/m2 1 times / day multiple, intravenous MTD Dose: 18 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 18 g/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10572607	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10572607
Neutropenia	grade 4, 83.3% DLT	18 g/m2 1 times / day multiple, intravenous MTD Dose: 18 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 18 g/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10572607	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10572607
Infection	severe, 33.3% DLT	18 g/m2 1 times / day multiple, intravenous MTD Dose: 18 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 18 g/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10572607	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10572607
Anemia	grade 4, 66.7% DLT	2.25 g/m2 1 times / day multiple, intravenous MTD Dose: 2.25 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 2.25 g/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11840607	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/11840607
Neutropenia	grade 4, 66.7% DLT	2.25 g/m2 1 times / day multiple, intravenous MTD Dose: 2.25 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 2.25 g/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11840607	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/11840607
Thrombocytopenia	grade 4, 66.7% DLT	2.25 g/m2 1 times / day multiple, intravenous MTD Dose: 2.25 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 2.25 g/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11840607	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/11840607
Febrile neutropenia	grade 5, 33.3% DLT, Disc. AE	2.25 g/m2 1 times / day multiple, intravenous MTD Dose: 2.25 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 2.25 g/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11840607	unhealthy, 45 Health Status: unhealthy Age Group: 45 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/11840607
Cystitis hemorrhagic	severe Disc. AE	1.2 g/m2 1 times / day multiple, intravenous Recommended Dose: 1.2 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 1.2 g/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019763s017lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019763s017lbl.pdf
Nephrotoxicity	severe Disc. AE	1.2 g/m2 1 times / day multiple, intravenous Recommended Dose: 1.2 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 1.2 g/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019763s017lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019763s017lbl.pdf
Renal failure	severe Disc. AE	1.2 g/m2 1 times / day multiple, intravenous Recommended Dose: 1.2 g/m2, 1 times / day Route: intravenous Route: multiple Dose: 1.2 g/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019763s017lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019763s017lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inducer 1087	substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2B6 776 CYP3A5 446 CYP2B1 12 CYP2C19 1119 CYP2A6 626 CYP2C8 810 UGT 219 alcohol dehydrogenase 7 ALDH1 3 P-gp 2052 OCT2 434 OAT1 395 OAT3 391 MRP1 113

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 2633	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/9157990/	yes
PXR 51	activator 342 Sources: https://pubmed.ncbi.nlm.nih.gov/24401834/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
OAT1 395	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/21077648/	no
OAT3 391	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/21077648/	no
P-gp 2052	substrate 4014 Sources: https://www.ingentaconnect.com/content/ben/cdth/2006/00000001/00000001/art00008	no
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/25934575/	poor
ALDH1 3	substrate 4014 Sources: https://www.ingentaconnect.com/content/ben/cdth/2006/00000001/00000001/art00008	yes	Aldoifosfamide 3
CYP2A6 626	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.3109/03602539709037591?journalCode=idmr20	yes
CYP2B1 12	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10326030/	yes
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/25934575/	yes
CYP2C8 810	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.3109/03602539709037591?journalCode=idmr20	yes
CYP3A5 446	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15875221/	yes
MRP1 113	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/26541366/	yes
OCT2 434	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/21077648/	yes
UGT 219	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/20541539/	yes	4-HYDROXYIFOSFAMIDE 3
alcohol dehydrogenase 7	substrate 4014 Sources: https://www.ingentaconnect.com/content/ben/cdth/2006/00000001/00000001/art00008	yes	4-HYDROXYIFOSFAMIDE 3
CYP2B6 776	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019763s020lbl.pdf#page=28 Page: 28.0	yes		no (co-administration study) Comment: Coadministration of ifosfamide with ketoconazole or rifampin did not produce changes inthe pharmacokinetics of the parent or metabolites that may result in an increased benefit of ifosfamidetherapy. (https://pubmed.ncbi.nlm.nih.gov/11503007/) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019763s020lbl.pdf#page=28 Page: 28.0
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019763s020lbl.pdf#page=28 Page: 28.0	yes		no (co-administration study) Comment: Coadministration of ifosfamide with ketoconazole or rifampin did not produce changes inthe pharmacokinetics of the parent or metabolites that may result in an increased benefit of ifosfamidetherapy. (https://pubmed.ncbi.nlm.nih.gov/11503007/) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019763s020lbl.pdf#page=28 Page: 28.0

PubMed

Title	Date	PubMed
Intratumoral injection of encapsulated cells producing an oxazaphosphorine activating cytochrome P450 for targeted chemotherapy.	1998	10026857
Prospective evaluation of high-dose ifosfamide-related nephrotoxicity in young adult patients with recurrent osteosarcoma previously treated with cisplatin, methotrexate and standard-dose ifosfamide.	1999 Jan	10194544
Injection of encapsulated cells producing an ifosfamide-activating cytochrome P450 for targeted chemotherapy to pancreatic tumors.	1999 Jun 30	10415878
Development of ifosfamide-induced nephrotoxicity: prospective follow-up in 75 patients.	1999 Mar	10064184
Risk factors for long-term outcome of ifosfamide-induced nephrotoxicity in children.	1999 May	10234592
Methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: report of 12 cases and a review of the literature.	2000 Jan	10646879
Subacute central nervous system degeneration in a child: an unusual manifestation of ifosfamide intoxication.	2000 Jul	10921521
Distinctive potentiating effects of cisplatin and/or ifosfamide combined with etoposide in human small cell lung carcinoma xenografts.	2000 May	10815935
Two episodes of ifosfamide-related neurotoxicity in the same patient following different schedules and doses of the drug. A case report.	2000 Nov-Dec	11218192
A phase II study of weekly alternating chemotherapy in extensive-stage small cell lung cancer.	2001	11338879
Comparison of double and triple high-dose chemotherapy with autologous blood stem cell transplantation in patients with metastatic breast cancer.	2001	11239170
[Post-operative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of German prospective randomised trial HIT'91].	2001 Apr	11355586
[Pigmented villonodular synovitis: apropos of 3 cases].	2001 Apr	11355581
The current status of docetaxel for advanced non-small cell lung cancer.	2001 Feb	11340898
Sustained response of sarcomatoid renal-cell carcinoma to MAID chemotherapy: case report and review of the literature.	2001 Feb	11300337
Selective use of whole-lung irradiation for patients with Ewing sarcoma family tumors and pulmonary metastases at the time of diagnosis.	2001 Feb	11216713
[Is it useful to perform a (67)gallium scintigraphy in the follow-up of patients with gastric lymphoma?].	2001 Feb	11181327
Adult Gaucher disease in association with primary malignant bone tumors.	2001 Feb 1	11169926
[Prostatic angiosarcoma: report of a new case].	2001 Jan	11284376
Anticancer drug-induced kidney disorders.	2001 Jan	11219485
Should we always choose a nonparametric test when comparing two apparently nonnormal distributions?	2001 Jan	11165471
Docetaxel and ifosfamide as second line treatment for patients with advanced or metastatic urothelial cancer after failure of platinum chemotherapy: a phase 2 study.	2001 Jan	11125366
Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children's Research Hospital OS-91 trial.	2001 Jan 1	11134210
A randomized trial of amifostine as a cytoprotective agent in patients receiving chemotherapy for small cell lung cancer.	2001 Jan 5	11139307
A phase II study of dose-intense ifosfamide plus epirubicin with hematopoietic growth factors for the treatment of patients with advanced soft tissue sarcomas; a novel sequential schedule.	2001 Mar	11320663
Gemcitabine for the treatment of non-small-cell lung cancer.	2001 Mar	11301846
Intrasellar rhabdomyosarcoma: case report.	2001 Mar	11270561
Topoisomerase IIalpha and other drug resistance markers in advanced non-small cell lung cancer.	2001 May	11325482
A novel alkylating agent, glufosfamide, enhances the activity of gemcitabine in vitro and in vivo.	2007 Aug	17786181

Patents

Sample Use Guides

In Vivo Use Guide

30-min infusion at a dose of 1.2 grams per m2 per day for 5 consecutive days

Route of Administration: Intravenous

In Vitro Use Guide

Human testicular germ cell tumour lines H 12.1 and 2102 EP were treated with ifosfamide at 50 mg kg-1 day-1.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 23:05:48 GMT 2025` Edited by `admin` on `Mon Mar 31 23:05:48 GMT 2025`
Record UNII	ARX5AJ985I
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ASTA-6569

Preferred Name

English

4-HYDROXYIFOSFAMIDE

Common Name

English

NSC-208841

Code

English

2H-1,3,2-OXAZAPHOSPHORIN-4-OL, 3-(2-CHLOROETHYL)-2-((2-CHLOROETHYL)AMINO)TETRAHYDRO-, 2-OXIDE

Systematic Name

English

4-HYDROXYISOPHOSPHAMIDE

Common Name

English

Code System Code Type Description

FDA UNII

ARX5AJ985I