Identification

Name
Ifosfamide
Accession Number
DB01181
Description

Ifosfamide is a chemotherapeutic agent chemically related to the nitrogen mustards and a synthetic analog of cyclophosphamide. It is active as an alkylating agent and an immunosuppressive agent.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 261.086
Monoisotopic: 260.02481966
Chemical Formula
C7H15Cl2N2O2P
Synonyms
  • 3-(2-chloroethyl)-2-((2-chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide
  • Ifosfamida
  • Ifosfamide
  • Ifosfamidum
  • Iphosphamide
  • Isofosfamide
  • Isophosphamide
  • Isosfamide
External IDs
  • Z4942

Pharmacology

Indication

Used as a component of various chemotherapeutic regimens as third-line therapy for recurrent or refractory germ cell testicular cancer. Also used as a component of various chemotherapeutic regimens for the treatment of cervical cancer, as well as in conjunction with surgery and/or radiation therapy in the treatment of various soft tissue sarcomas. Other indications include treatment of osteosarcoma, bladder cancer, ovarian cancer. small cell lung cancer, and non-Hodgkin's lymphoma.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Ifosfamide requires activation by microsomal liver enzymes to active metabolites in order to exert its cytotoxic effects. Activation occurs by hydroxylation at the ring carbon atom 4 to form the unstable intermediate 4-hydroxyifosfamide. This metabolite than rapidly degrades to the stable urinary metabolite 4-ketoifosfamide. The stable urinary metabolite, 4-carboxyifosfamide, is formed upon opening of the ring. These urinary metabolites have not been found to be cytotoxic. N, N-bis (2-chloroethyl)-phosphoric acid diamide (ifosphoramide) and acrolein are also found. The major urinary metabolites, dechloroethyl ifosfamide and dechloroethyl cyclophosphamide, are formed upon enzymatic oxidation of the chloroethyl side chains and subsequent dealkylation. It is the alkylated metabolites of ifosfamide that have been shown to interact with DNA. Ifosfamide is cycle-phase nonspecific.

Mechanism of action

The exact mechanism of ifosfamide has not been determined, but appears to be similar to other alkylating agents. Ifosfamide requires biotransformation in the liver by mixed-function oxidases (cytochrome P450 system) before it becomes active. After metabolic activation, active metabolites of ifosfamide alkylate or bind with many intracellular molecular structures, including nucleic acids. The cytotoxic action is primarily through the alkylation of DNA, done by attaching the N-7 position of guanine to its reactive electrophilic groups. The formation of inter and intra strand cross-links in the DNA results in cell death.

TargetActionsOrganism
ADNA
other/unknown
Humans
UNuclear receptor subfamily 1 group I member 2Not AvailableHumans
Absorption
Not Available
Volume of distribution

Ifosfamide volume of distribution (Vd) approximates the total body water volume, suggesting that distribution takes place with minimal tissue binding. Following intravenous administration of 1.5 g/m2 over 0.5 hour once daily for 5 days to 15 patients with neoplastic disease, the median Vd of ifosfamide was 0.64 L/kg on Day 1 and 0.72 L/kg on Day 5. When given to pediatric patients, the volume of distribution was 21±1.6 L/m^2.

Protein binding

Ifosfamide shows little plasma protein binding.

Metabolism

Primarily hepatic. Ifosfamide is metabolized through two metabolic pathways: ring oxidation ("activation") to form the active metabolite, 4-hydroxy-ifosfamide and side-chain oxidation to form the inactive metabolites, 3-dechloro-ethylifosfamide or 2-dechloroethylifosfamide with liberation of the toxic metabolite, chloroacetaldehyde. Small quantities (nmol/mL) of ifosfamide mustard and 4-hydroxyifosfamide are detectable in human plasma. Metabolism of ifosfamide is required for the generation of the biologically active species and while metabolism is extensive, it is also quite variable among patients.

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Route of elimination

Ifosfamide is extensively metabolized in humans and the metabolic pathways appear to be saturated at high doses. After administration of doses of 5 g/m2 of 14C-labeled ifosfamide, from 70% to 86% of the dosed radioactivity was recovered in the urine, with about 61% of the dose excreted as parent compound. At doses of 1.6–2.4 g/m2 only 12% to 18% of the dose was excreted in the urine as unchanged drug within 72 hours.

Half-life

7-15 hours. The elimination half-life increase appeared to be related to the increase in ifosfamide volume of distribution with age.

Clearance
  • 2.4±0.33 L/h/m^2 [pediatric patients]
Adverse Effects
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Toxicity

LD50 (mouse) = 390-1005 mg/kg, LD50 (rat) = 150-190 mg/kg. Side effects include nausea, vomiting and myelosuppression. Toxic effects include central nervous system toxicity (confusion, hallucinations) and urotoxic effects (cystitis, blood in urine).

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Ifosfamide Metabolism PathwayDrug metabolism
Ifosfamide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Ifosfamide which could result in a higher serum level.
AbametapirThe serum concentration of Ifosfamide can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Ifosfamide can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Ifosfamide is combined with Abciximab.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Ifosfamide.
AbirateroneThe metabolism of Ifosfamide can be decreased when combined with Abiraterone.
AcalabrutinibThe metabolism of Ifosfamide can be increased when combined with Acalabrutinib.
AcarboseAcarbose may decrease the excretion rate of Ifosfamide which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Ifosfamide which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Ifosfamide which could result in a higher serum level.
Additional Data Available
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  • Severity
    Severity
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  • Evidence Level
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  • Action
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Food Interactions
  • Avoid alcohol. Ingesting alcohol may worsen nausea and vomiting caused by ifosfamide.
  • Exercise caution with grapefruit products. Grapefruit inhibits the CYP3A4 metabolism of ifosfamide to its active metabolite, therefore reducing its efficacy.
  • Exercise caution with St. John's Wort. Close monitoring is warranted as this herb induces the CYP3A4 metabolism of ifosfamide to its alkylating active metabolites, including, chloroacetaldehyde, a nephrotoxic and neurotoxic metabolite.

Products

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International/Other Brands
Celofos (Celon) / Cuantil (Teva) / Holoxan (Baxter) / Mitoxana (Baxter)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IfexInjection, powder, for solution1 g/20mLIntravenousBaxter Healthcare Corporation1988-12-30Not applicableUS flag
IfexInjection, powder, for solution3 g/60mLIntravenousE.R. Squibb & Sons, L.L.C.2009-06-012012-03-31US flag
IfexPowder, for solution1 gIntravenousBaxter Laboratories2001-03-20Not applicableCanada flag
IfexInjection, powder, for solution1 g/20mLIntravenousE.R. Squibb & Sons, L.L.C.2009-06-012012-01-31US flag
IfexPowder, for solution3 gIntravenousBaxter Laboratories2001-01-25Not applicableCanada flag
IfexInjection, powder, for solution3 g/60mLIntravenousBaxter Healthcare Corporation1988-12-30Not applicableUS flag
Ifex Pws 1gm/vialPowder, for solutionIntravenousBristol Labs Division Of Bristol Myers Squibb1989-12-312001-04-09Canada flag
Ifex Pws 2g/vialPowder, for solutionIntravenousBristol Labs Division Of Bristol Myers Squibb1989-12-311997-08-14Canada flag
Ifex Pws 3gm/vialPowder, for solutionIntravenousBristol Labs Division Of Bristol Myers Squibb1989-12-312002-07-11Canada flag
IfosfamideInjection, powder, for solution3 g/60mLIntravenousBaxter Healthcare Corporation1988-12-30Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IfosfamideInjection50 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.2017-06-10Not applicableUS flag
IfosfamideInjection, solution1 g/20mLIntravenousTeva Parenteral Medicines, Inc.2007-07-26Not applicableUS flag
IfosfamideInjection, solution50 mg/1mLIntravenousMylan Institutional2012-11-272017-12-31US flag
IfosfamideInjection50 mg/1mLIntravenousBedford Pharmaceuticals2010-08-312010-09-01US flag
IfosfamideInjection, solution50 mg/1mLIntravenousFresenius Kabi USA, LLC2009-09-302012-07-31US flag
IfosfamideInjection, powder, lyophilized, for solution1 g/1IntravenousFresenius Kabi USA, LLC2003-01-28Not applicableUS flag
IfosfamideInjection, solution50 mg/1mLIntravenousPfizer Laboratories Div Pfizer Inc.2012-11-272017-12-31US flag
IfosfamideInjection, solution50 mg/1mLIntravenousMylan Institutional2012-11-272017-12-31US flag
IfosfamideInjection50 mg/1mLIntravenousHikma Pharmaceuticals USA Inc.2017-06-10Not applicableUS flag
IfosfamideInjection50 mg/1mLIntravenousBedford Pharmaceuticals2010-08-312010-09-01US flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
IFEX and MESNEXIfosfamide (1 g/20mL) + Mesna (100 mg/1mL)KitIntravenousE.R. Squibb & Sons, L.L.C.2009-06-012010-06-30US flag
IFEX and MESNEXIfosfamide (1 g/20mL) + Mesna (100 mg/1mL)KitIntravenousE.R. Squibb & Sons, L.L.C.2009-06-012010-06-30US flag
IFEX and MESNEXIfosfamide (3 g/60mL) + Mesna (100 mg/1mL)KitIntravenousE.R. Squibb & Sons, L.L.C.2009-06-012010-03-31US flag
Ifosfamide and MesnaIfosfamide (3 g/60mL) + Mesna (100 mg/1mL)KitIntravenousTeva Parenteral Medicines, Inc.2012-09-262012-09-26US flag
Ifosfamide and MesnaIfosfamide (1 g/20mL) + Mesna (100 mg/1mL)KitIntravenousTeva Parenteral Medicines, Inc.2012-09-262012-09-26US flag
Ifosfamide and MesnaIfosfamide (1 g/20mL) + Mesna (100 mg/1mL)KitIntravenousTeva Parenteral Medicines, Inc.2002-05-012011-07-31US flag

Categories

ATC Codes
L01AA06 — Ifosfamide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as isofamides. These are oxazaphospholanes containing the isofamide skeleton. Isofamide is a heterocyclic compound made up of a 1,3,2-oxazaphospholane, where the phosphorus atom is part of a phosphodiamide group, and the oxazaphospholane is substituted by two haloalkyl chains.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Oxazaphosphinanes
Sub Class
Isofamides
Direct Parent
Isofamides
Alternative Parents
Phosphoric monoester diamides / Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives / Alkyl chlorides
Substituents
Aliphatic heteromonocyclic compound / Alkyl chloride / Alkyl halide / Azacycle / Hydrocarbon derivative / Isofamide / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organic phosphoric acid amide
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
ifosfamides (CHEBI:5864)

Chemical Identifiers

UNII
UM20QQM95Y
CAS number
3778-73-2
InChI Key
HOMGKSMUEGBAAB-UHFFFAOYSA-N
InChI
InChI=1S/C7H15Cl2N2O2P/c8-2-4-10-14(12)11(6-3-9)5-1-7-13-14/h1-7H2,(H,10,12)
IUPAC Name
3-(2-chloroethyl)-2-[(2-chloroethyl)amino]-1,3,2λ⁵-oxazaphosphinan-2-one
SMILES
ClCCNP1(=O)OCCCN1CCCl

References

Synthesis Reference

U.S. Patent 3,732,340.

US3732340
General References
  1. Furlanut M, Franceschi L: Pharmacology of ifosfamide. Oncology. 2003;65 Suppl 2:2-6. [PubMed:14586139]
  2. Fleming RA: An overview of cyclophosphamide and ifosfamide pharmacology. Pharmacotherapy. 1997 Sep-Oct;17(5 Pt 2):146S-154S. [PubMed:9322882]
  3. Wagner T: Ifosfamide clinical pharmacokinetics. Clin Pharmacokinet. 1994 Jun;26(6):439-56. [PubMed:8070218]
  4. Allen LM, Creaven PJ, Nelson RL: Studies on the human pharmacokinetics of isophosphamide (NSC-109724). Cancer Treat Rep. 1976 Apr;60(4):451-8. [PubMed:1277221]
  5. Brade WP, Herdrich K, Varini M: Ifosfamide--pharmacology, safety and therapeutic potential. Cancer Treat Rev. 1985 Mar;12(1):1-47. [PubMed:3896483]
  6. Zalupski M, Baker LH: Ifosfamide. J Natl Cancer Inst. 1988 Jun 15;80(8):556-66. [PubMed:3286879]
  7. Willits I, Price L, Parry A, Tilby MJ, Ford D, Cholerton S, Pearson AD, Boddy AV: Pharmacokinetics and metabolism of ifosfamide in relation to DNA damage assessed by the COMET assay in children with cancer. Br J Cancer. 2005 May 9;92(9):1626-35. [PubMed:15827549]
  8. Lokiec F: Ifosfamide: pharmacokinetic properties for central nervous system metastasis prevention. Ann Oncol. 2006 May;17 Suppl 4:iv33-6. [PubMed:16702183]
  9. Schoenike SE, Dana WJ: Ifosfamide and mesna. Clin Pharm. 1990 Mar;9(3):179-91. [PubMed:2107997]
  10. Dechant KL, Brogden RN, Pilkington T, Faulds D: Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. Drugs. 1991 Sep;42(3):428-67. [PubMed:1720382]
Human Metabolome Database
HMDB0015312
KEGG Drug
D00343
KEGG Compound
C07047
PubChem Compound
3690
PubChem Substance
46508335
ChemSpider
3562
BindingDB
189358
RxNav
5657
ChEBI
5864
ChEMBL
CHEMBL1024
Therapeutic Targets Database
DAP000537
PharmGKB
PA449964
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ifosfamide
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
MSDS
Download (293 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentSoft Tissue Sarcoma (STS)1
4CompletedTreatmentAdult Acute Lymphocytic Leukemia3
4CompletedTreatmentBurkitt's Lymphoma / Large Cell Anaplastic Lymphoma / Lymphoma, Lymphoblastic / Mediastinal Neoplasms1
4RecruitingTreatmentPeripheral T Cell Lymphoma (PTCL) / Peripheral T-Cell Lymphoma (PTCL)1
4Unknown StatusTreatmentAcute Lymphoblastic Leukaemias (ALL) / Non-Hodgkin's Lymphoma (NHL)1
4Unknown StatusTreatmentALK-negative Anaplastic Large Cell Lymphoma / Angioimmunoblastic T Cell Lymphoma / Angioimmunoblastic T-Cell Lymphoma / Enteropathy Associated T Cell Lymphoma / Enteropathy-Associated T-Cell Lymphoma / Hepatosplenic T Cell Lymphoma / Hepatosplenic T-Cell Lymphoma / Peripherial T Cell Lymphoma,Not Otherwise Specified / Subcutaneous Panniculitis Like T Cell Lymphoma1
4Unknown StatusTreatmentIntracranial Germ Cell Tumors1
3Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3Active Not RecruitingTreatmentAdult T Acute Lymphoblastic Leukemia / Ann Arbor Stage II Adult Lymphoblastic Lymphoma / Ann Arbor Stage II Childhood Lymphoblastic Lymphoma / Ann Arbor Stage III Adult Lymphoblastic Lymphoma / Ann Arbor Stage III Childhood Lymphoblastic Lymphoma / Ann Arbor Stage IV Adult Lymphoblastic Lymphoma / Ann Arbor Stage IV Childhood Lymphoblastic Lymphoma / Childhood T Acute Lymphoblastic Leukemia1
3Active Not RecruitingTreatmentEwing's Sarcoma (ES)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • APP Pharmaceuticals
  • Baxter International Inc.
  • Bristol-Myers Squibb Co.
  • Teva Pharmaceutical Industries Ltd.
Dosage Forms
FormRouteStrength
Injection, powder, for solution
Injection, powder, for solutionIntravenous200 mg
Injection, powder, for solutionIntravenous500 mg
Injection, powder, for solutionParenteral1 G
Injection, solutionIntravenous1 G/25ML
Injection, solutionIntravenous2 G/50ML
Injection, solution, concentrateIntravenous1 g
Injection, solution, concentrateIntravenous500 mg
Powder, for solutionIntravenous2 G
Injection, solutionIntravenous0.5 g
Injection, powder, for solution1 g
Injection, solutionIntravenous1 g
Injection, powder, for solution2 g
Injection, solutionIntravenous2 g
Injection, powder, for solutionIntravenous1 g/20mL
Injection, powder, for solutionIntravenous3 g/60mL
Powder, for solutionIntravenous1 g
Powder, for solutionIntravenous3 g
KitIntravenous
Powder, for solutionIntravenous
Injection, solution, concentrateIntravenous1 g/25mL
Injection, powder, lyophilized, for solutionIntravenous1000 mg
Injection, powder, lyophilized, for solutionIntravenous1 g
Injection, powder, for solutionIntravenous1 g
InjectionIntravenous50 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous1 g/1
Injection, solutionIntravenous1 g/20mL
Injection, solutionIntravenous3 g/60mL
Injection, solutionIntravenous50 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous2 g
Prices
Unit descriptionCostUnit
Ifex-mesnex kit2709.98USD kit
Ifosfamide-mesna kit787.5USD kit
Ifex 3 gm vial489.13USD vial
Ifex 1 gm vial163.04USD vial
Ifosfamide 3 gm vial114.0USD vial
Ifosfamide 1 gm vial56.4USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5252341No1993-10-122011-07-16US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)39-41 °CU.S. Patent 3,732,340.
water solubility3780 mg/LNot Available
logP0.86HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility15.0 mg/mLALOGPS
logP0.57ALOGPS
logP0.097ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)13.24ChemAxon
pKa (Strongest Basic)0.12ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area41.57 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity58.48 m3·mol-1ChemAxon
Polarizability23.94 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9807
Blood Brain Barrier+0.9736
Caco-2 permeable-0.5411
P-glycoprotein substrateNon-substrate0.7098
P-glycoprotein inhibitor INon-inhibitor0.6204
P-glycoprotein inhibitor IINon-inhibitor0.9617
Renal organic cation transporterNon-inhibitor0.8135
CYP450 2C9 substrateNon-substrate0.7674
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5922
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8835
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9723
Ames testAMES toxic0.9108
CarcinogenicityNon-carcinogens0.8903
BiodegradationNot ready biodegradable0.7807
Rat acute toxicity3.2294 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.8985
hERG inhibition (predictor II)Non-inhibitor0.8224
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0490000000-17ba12fd0e00df2723dc
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0090000000-d4e1a660175509162e8c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0090000000-c26cb9c6b0b1cafbc7c2
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0gx3-6960000000-e4f4eadda4e355e7dd84
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0f6x-8900000000-10d5b2623785719eb1e7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9500000000-d06de43b506b64b21f31
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9300000000-698d7a6ed4f1837ad721
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0090000000-084cc16ffb95bd0ef960
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0090000000-1ae1b6f01a6e1a37e34c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0gx3-6960000000-ad40c4b969e8d0286677
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0f6x-8900000000-137610f53c637d8d5b79
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9500000000-6b78178980477a0f7c08
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9200000000-e6f6b95f30fc4c9fde8a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-0490000000-661cabcd304902a3d4b5
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-0290000000-4c400c6848932e5bc304
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-1390000000-cb6bb34e3efac3f15b24
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-3910000000-2729bcf5701a78198ad5
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Targets

Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Other/unknown
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
References
  1. Furlanut M, Franceschi L: Pharmacology of ifosfamide. Oncology. 2003;65 Suppl 2:2-6. [PubMed:14586139]
  2. Hartley JM, Spanswick VJ, Gander M, Giacomini G, Whelan J, Souhami RL, Hartley JA: Measurement of DNA cross-linking in patients on ifosfamide therapy using the single cell gel electrophoresis (comet) assay. Clin Cancer Res. 1999 Mar;5(3):507-12. [PubMed:10100700]
  3. Willits I, Price L, Parry A, Tilby MJ, Ford D, Cholerton S, Pearson AD, Boddy AV: Pharmacokinetics and metabolism of ifosfamide in relation to DNA damage assessed by the COMET assay in children with cancer. Br J Cancer. 2005 May 9;92(9):1626-35. [PubMed:15827549]
  4. Lokiec F: Ifosfamide: pharmacokinetic properties for central nervous system metastasis prevention. Ann Oncol. 2006 May;17 Suppl 4:iv33-6. [PubMed:16702183]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Harmsen S, Meijerman I, Beijnen JH, Schellens JH: Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor. Cancer Chemother Pharmacol. 2009 Jun;64(1):35-43. doi: 10.1007/s00280-008-0842-3. Epub 2008 Oct 7. [PubMed:18839173]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Lokiec F: Ifosfamide: pharmacokinetic properties for central nervous system metastasis prevention. Ann Oncol. 2006 May;17 Suppl 4:iv33-6. [PubMed:16702183]
  2. Chen CS, Jounaidi Y, Waxman DJ: Enantioselective metabolism and cytotoxicity of R-ifosfamide and S-ifosfamide by tumor cell-expressed cytochromes P450. Drug Metab Dispos. 2005 Sep;33(9):1261-7. Epub 2005 May 26. [PubMed:15919850]
  3. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  4. Roy P, Yu LJ, Crespi CL, Waxman DJ: Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos. 1999 Jun;27(6):655-66. [PubMed:10348794]
  5. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Lokiec F: Ifosfamide: pharmacokinetic properties for central nervous system metastasis prevention. Ann Oncol. 2006 May;17 Suppl 4:iv33-6. [PubMed:16702183]
  2. Chen CS, Jounaidi Y, Waxman DJ: Enantioselective metabolism and cytotoxicity of R-ifosfamide and S-ifosfamide by tumor cell-expressed cytochromes P450. Drug Metab Dispos. 2005 Sep;33(9):1261-7. Epub 2005 May 26. [PubMed:15919850]
  3. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  4. Roy P, Yu LJ, Crespi CL, Waxman DJ: Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos. 1999 Jun;27(6):655-66. [PubMed:10348794]
  5. Preiss R, Schmidt R, Baumann F, Hanschmann H, Hauss J, Geissler F, Pahlig H, Ratzewiss B: Measurement of 4-hydroxylation of ifosfamide in human liver microsomes using the estimation of free and protein-bound acrolein and codetermination of keto- and carboxyifosfamide. J Cancer Res Clin Oncol. 2002 Jul;128(7):385-92. Epub 2002 Jun 11. [PubMed:12136253]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Lokiec F: Ifosfamide: pharmacokinetic properties for central nervous system metastasis prevention. Ann Oncol. 2006 May;17 Suppl 4:iv33-6. [PubMed:16702183]
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  3. Roy P, Yu LJ, Crespi CL, Waxman DJ: Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos. 1999 Jun;27(6):655-66. [PubMed:10348794]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Roy P, Yu LJ, Crespi CL, Waxman DJ: Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos. 1999 Jun;27(6):655-66. [PubMed:10348794]
  2. Lokiec F: Ifosfamide: pharmacokinetic properties for central nervous system metastasis prevention. Ann Oncol. 2006 May;17 Suppl 4:iv33-6. [PubMed:16702183]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Lokiec F: Ifosfamide: pharmacokinetic properties for central nervous system metastasis prevention. Ann Oncol. 2006 May;17 Suppl 4:iv33-6. [PubMed:16702183]
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  3. Schmidt R, Baumann F, Knupfer H, Brauckhoff M, Horn LC, Schonfelder M, Kohler U, Preiss R: CYP3A4, CYP2C9 and CYP2B6 expression and ifosfamide turnover in breast cancer tissue microsomes. Br J Cancer. 2004 Feb 23;90(4):911-6. doi: 10.1038/sj.bjc.6601492. [PubMed:14970873]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Lokiec F: Ifosfamide: pharmacokinetic properties for central nervous system metastasis prevention. Ann Oncol. 2006 May;17 Suppl 4:iv33-6. [PubMed:16702183]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Lokiec F: Ifosfamide: pharmacokinetic properties for central nervous system metastasis prevention. Ann Oncol. 2006 May;17 Suppl 4:iv33-6. [PubMed:16702183]
  2. Roy P, Yu LJ, Crespi CL, Waxman DJ: Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos. 1999 Jun;27(6):655-66. [PubMed:10348794]
  3. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C18
Uniprot ID
P33260
Uniprot Name
Cytochrome P450 2C18
Molecular Weight
55710.075 Da
References
  1. Roy P, Yu LJ, Crespi CL, Waxman DJ: Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos. 1999 Jun;27(6):655-66. [PubMed:10348794]
  2. Chang TK, Yu L, Goldstein JA, Waxman DJ: Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE359 allele as low-Km catalysts of cyclophosphamide and ifosfamide activation. Pharmacogenetics. 1997 Jun;7(3):211-21. [PubMed:9241661]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]

Drug created on June 13, 2005 07:24 / Updated on November 23, 2020 09:08

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