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

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

Description

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	Crosslinking Agent 83

Conditions

Condition	Modality	Targets	Highest Phase	Product
Germ cell testicular cancer 3	Primary		Approved 8,583	IFEX

C_max

Value	Dose	Analyte	Population
346 μM	3 g/m² single, intravenous	IFOSFAMIDE plasma	Homo sapiens
200 μM	1.5 g/m² single, oral	IFOSFAMIDE plasma	Homo sapiens
203 μM	1.5 g/m² single, intravenous	IFOSFAMIDE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
2197 mM × h	3 g/m² single, intravenous	IFOSFAMIDE plasma	Homo sapiens
1360 μM × h	1.5 g/m² single, oral	IFOSFAMIDE plasma	Homo sapiens
1520 μM × h	1.5 g/m² single, intravenous	IFOSFAMIDE plasma	Homo sapiens
7.54 mM × h	3 g/m² 1 times / day multiple, intravenous	IFOSFAMIDE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
4.33 h	3 g/m² single, intravenous	IFOSFAMIDE plasma	Homo sapiens
5 h	1.5 g/m² single, oral	IFOSFAMIDE plasma	Homo sapiens
5.6 h	1.5 g/m² single, intravenous	IFOSFAMIDE plasma	Homo sapiens
2.12 h	3 g/m² 1 times / day multiple, intravenous	IFOSFAMIDE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
100%	unknown		IFOSFAMIDE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
18 g/m2 1 times / day multiple, intravenous MTD	unhealthy, 45	DLT: Neutropenia, Infection...
2.25 g/m2 1 times / day multiple, intravenous MTD	unhealthy, 45	DLT: Neutropenia, Febrile neutropenia...
1.2 g/m2 1 times / day multiple, intravenous Recommended	unhealthy	Disc. AE: Nephrotoxicity, Renal failure...

Showing 1 to 3 of 3 entries

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AEs

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AE	Significance	Dose	Population
Thrombocytopenia	grade 4, 66.7% DLT	18 g/m2 1 times / day multiple, intravenous MTD	unhealthy, 45
Neutropenia	grade 4, 83.3% DLT	18 g/m2 1 times / day multiple, intravenous MTD	unhealthy, 45
Infection	severe, 33.3% DLT	18 g/m2 1 times / day multiple, intravenous MTD	unhealthy, 45
Anemia	grade 4, 66.7% DLT	2.25 g/m2 1 times / day multiple, intravenous MTD	unhealthy, 45
Neutropenia	grade 4, 66.7% DLT	2.25 g/m2 1 times / day multiple, intravenous MTD	unhealthy, 45

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,946 inducer 1,087	substrate 1,193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2B6 776 CYP3A5 446 CYP2B1 12 CYP2C19 1,119 CYP2A6 626 CYP2C8 810 UGT 219 alcohol dehydrogenase 7 ALDH1 3 P-gp 2,052 OCT2 434 OAT1 395 OAT3 391 MRP1 113

Drug as perpetrator

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Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 2,633	inducer 1,966	yes
PXR 51	activator 342	yes

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Drug as victim

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Target	Modality	Activity	Metabolite
OAT1 395	substrate 4,014	no
OAT3 391	substrate 4,014	no
P-gp 2,052	substrate 4,014	no
CYP2C9 1,193	substrate 4,014	poor
ALDH1 3	substrate 4,014	yes	Aldoifosfamide 3

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PubMed

Show entries

Title	Date	PubMed
Targeted chemotherapy by intratumour injection of encapsulated cells engineered to produce CYP2B1, an ifosfamide activating cytochrome P450.	1998 Aug	10326030
Deletions in the mitochondrial DNA and decrease in the oxidative phosphorylation activity of children with Fanconi syndrome secondary to antiblastic therapy.	1999 Jul	10401022
L-Histidinol attenuates Fanconi syndrome induced by ifosfamide in rats.	1999 Jul-Aug	10450020
Injection of encapsulated cells producing an ifosfamide-activating cytochrome P450 for targeted chemotherapy to pancreatic tumors.	1999 Jun 30	10415878
Characterization of a human cell clone expressing cytochrome P450 for safe use in human somatic cell therapy.	1999 Jun 30	10415877

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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.

Show entries

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

Showing 1 to 5 of 5 entries

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Show entries

Code System

Code

Type

Description

FDA UNII

ARX5AJ985I

PRIMARY

CAS

50892-10-9

PRIMARY

EPA CompTox

DTXSID90308749

PRIMARY

PUBCHEM

308171

PRIMARY

NSC

208841

PRIMARY

Showing 1 to 5 of 5 entries

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ACTIVE MOIETY


					ARX5AJ985I

4-HYDROXYIFOSFAMIDE

METABOLITE (PARENT)


					H49U38I97X

IFOSFAMIDE-4-(2-THIOETHYLSULPHONIC ACID)

PRODRUG (METABOLITE ACTIVE)


					1W5N8SZD9A

GLUFOSFAMIDE

PRODRUG (METABOLITE ACTIVE)


					UM20QQM95Y

IFOSFAMIDE

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator