IFOSFAMIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C7H15Cl2N2O2P
Molecular Weight	261.086
Optical Activity	( + / - )
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

ClCCNP1(=O)OCCCN1CCCl

InChI

InChIKey=HOMGKSMUEGBAAB-UHFFFAOYSA-N

InChI=1S/C7H15Cl2N2O2P/c8-2-4-10-14(12)11(6-3-9)5-1-7-13-14/h1-7H2,(H,10,12)

HIDE SMILES / InChI

Molecular Formula	C7H15Cl2N2O2P
Molecular Weight	261.086
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

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 278	Crosslinking Agent 81

Conditions

Condition	Modality	Targets	Highest Phase	Product
Germ cell testicular cancer 3	Primary		Approved 8,429	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

Show entries

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 1,737 inducer 781	substrate 1,037

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2B6 664 CYP3A5 395 CYP2B1 12 CYP2C19 991 CYP2A6 543 CYP2C8 693 UGT 192 alcohol dehydrogenase 7 ALDH1 3 P-gp 1,537 OCT2 355 OAT1 326 OAT3 339 MRP1 107

Drug as perpetrator

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Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1,925	inducer 1,573	yes
PXR 46	activator 214	yes

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Drug as victim

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Target	Modality	Activity	Metabolite
OAT1 326	substrate 3,367	no
OAT3 339	substrate 3,367	no
P-gp 1,537	substrate 3,367	no
CYP2C9 1,037	substrate 3,367	poor
ALDH1 3	substrate 3,367	yes	Aldoifosfamide 3

Showing 1 to 5 of 16 entries

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PubMed

Show entries

Title	Date	PubMed
Taurine attenuates fanconi syndrome induced by ifosfamide without compromising its antitumor activity.	1998	10063969
Intratumoral injection of encapsulated cells producing an oxazaphosphorine activating cytochrome P450 for targeted chemotherapy.	1998	10026857
Anticancer drug sensitivity and expression of multidrug resistance markers in early passage human sarcomas.	1999 Aug	10473106
Risk factors for long-term outcome of ifosfamide-induced nephrotoxicity in children.	1999 May	10234592
Primary desmoplastic small cell tumor of soft tissues and bone of the hand.	1999 Nov	10555010