Cyclophosphamide

Identification

Name
Cyclophosphamide
Accession Number
DB00531
Description

Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 261.086
Monoisotopic: 260.02481966
Chemical Formula
C7H15Cl2N2O2P
Synonyms
  • (+-)-Cyclophosphamide
  • (RS)-Cyclophosphamide
  • 2-[Bis(2-chloroethylamino)]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide
  • Anhydrous cyclophosphamide
  • Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester
  • Ciclofosfamida
  • Ciclofosfamide
  • Cyclophosphamid
  • Cyclophosphamide
  • Cyclophosphamide anhydrous
  • Cyclophosphamidum
  • Cytophosphane
  • N,N-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide
External IDs
  • B 518
  • NSC 26271
  • RCRA Waste Number U058

Pharmacology

Indication

Cyclophosphamide is indicated for the treatment of malignant lymphomas, multiple myeloma, leukemias, mycosis fungoides (advanced disease), neuroblastoma (disseminated disease), adenocarcinoma of the ovary, retinoblastoma, and carcinoma of the breast. It is also indicated for the treatment of biopsy-proven minimal change nephrotic syndrome in pediatric patients.

Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Cyclophosphamide is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.

Mechanism of action

Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.

TargetActionsOrganism
ADNA
cross-linking/alkylation
Humans
UNuclear receptor subfamily 1 group I member 2Not AvailableHumans
Absorption

After oral administration, peak concentrations occur at one hour.

Volume of distribution

30-50 L

Protein binding

20% of cyclophosphamide is protein bound with no dose dependent changes. Some metabolites are protein bound to an extent greater than 60%.

Metabolism

Metabolism and activation occurs at the liver. 75% of the drug is activated by cytochrome P450 isoforms, CYP2A6, 2B6, 3A4, 3A5, 2C9, 2C18, and 2C19. The CYP2B6 isoform is the enzyme with the highest 4-hydroxylase activity. Cyclophosphamide undergoes activation to eventually form active metabolites, phosphoramide mustard and acrolein. Cyclophosphamide appears to induce its own metabolism which results in an overall increase in clearance, increased formation of 4-hydroxyl metabolites, and shortened t1/2 values following repeated administration.

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Route of elimination

Cyclophosphamide is eliminated primarily in the form of metabolites. 10-20% is excreted unchanged in the urine and 4% is excreted in the bile following IV administration.

Half-life

3-12 hours

Clearance

Total body clearance = 63 ± 7.6 L/kg.

Adverse Effects
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Toxicity

Adverse reactions reported most often include neutropenia, febrile neutropenia, fever, alopecia, nausea, vomiting, and diarrhea.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Cyclophosphamide Action PathwayDrug action
Cyclophosphamide Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 3A4CYP3A4*1B(G;G) / (A;G)G AllelleEffect Directly StudiedPatients with this genotype have reduced metabolism of cyclophosphamide to its active form and reduced disease free survival time when using cyclophosphamide to treat node-positive breast cancer.Details
Cytochrome P450 2B6CYP2B6*1G(C;C) / (C;T)C AllelleEffect Directly StudiedPatients with this genotype have reduced metabolism of cyclophosphamide to its active form.Details

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
AbametapirThe serum concentration of Cyclophosphamide can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Cyclophosphamide can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Cyclophosphamide.
AbirateroneThe metabolism of Cyclophosphamide can be increased when combined with Abiraterone.
AcalabrutinibThe metabolism of Cyclophosphamide can be increased when combined with Acalabrutinib.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be increased when used in combination with Cyclophosphamide.
AcetaminophenThe risk or severity of methemoglobinemia can be increased when Acetaminophen is combined with Cyclophosphamide.
AcetohexamideThe metabolism of Cyclophosphamide can be decreased when combined with Acetohexamide.
AcetophenazineCyclophosphamide may increase the neurotoxic activities of Acetophenazine.
Acetyl sulfisoxazoleThe metabolism of Cyclophosphamide can be decreased when combined with Acetyl sulfisoxazole.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Drink plenty of fluids. Drink 2 to 3 liters of fluids a day.
  • Take with food. Food reduces irritation.

Products

Product Ingredients
IngredientUNIICASInChI Key
Cyclophosphamide monohydrate8N3DW7272P6055-19-2PWOQRKCAHTVFLB-UHFFFAOYSA-N
Product Images
International/Other Brands
Endoxan (Actavis) / Neosar / Procytox (Baxter) / Revimmune / Sendoxan (Baxter)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CyclophosphamideInjection, powder, lyophilized, for solution500 mg/25mLIntravenous; OralBaxter Healthcare Corporation1959-11-162019-05-06US flag
CyclophosphamideCapsule25 mg/1OralAvera McKennan Hospital2015-08-182017-05-24US flag
CyclophosphamideInjection, powder, lyophilized, for solution2 g/100mLIntravenous; OralBaxter Healthcare Corporation1959-11-162019-05-06US flag
CyclophosphamideInjection, solution200 mg/1mLIntravenousIngenus Pharmaceuticals, LLC2020-07-31Not applicableUS flag
CyclophosphamideTablet50 mg/1OralBaxter Healthcare Corporation2020-08-07Not applicableUS flag
CyclophosphamideCapsule50 mg/1OralWest-Ward Pharmaceuticals Corp.2013-09-16Not applicableUS flag
CyclophosphamideInjection, powder, lyophilized, for solution1 g/50mLIntravenous; OralBaxter Healthcare Corporation1959-11-162019-05-06US flag
CyclophosphamideCapsule50 mg/1OralAvera McKennan Hospital2015-04-232017-05-24US flag
CyclophosphamideInjection, solution200 mg/1mLIntravenousIngenus Pharmaceuticals, LLC2020-07-31Not applicableUS flag
CyclophosphamideCapsule25 mg/1OralWest-Ward Pharmaceuticals Corp.2013-09-16Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    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

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

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CyclophosphamideCapsule25 mg/1OralANI Pharmaceuticals, Inc.2018-03-20Not applicableUS flag
CyclophosphamideCapsule50 mg/1OralANI Pharmaceuticals, Inc.2020-06-22Not applicableUS flag
CyclophosphamideInjection, powder, for solution2 g/100mLIntravenous; OralBaxter Healthcare Corporation2008-05-21Not applicableUS flag
CyclophosphamideInjection, powder, for solution500 mg/25mLIntravenous; OralAmneal Pharmaceuticals LLC2018-05-31Not applicableUS flag
CyclophosphamideTablet25 mg/1OralRoxane Laboratories1999-08-172016-07-11US flag
CyclophosphamideInjection, powder, for solution1 g/50mLIntravenous; OralBaxter Healthcare Corporation2008-05-21Not applicableUS flag
CyclophosphamideInjection, powder, for solution1 g/50mLIntravenous; OralBaxter Healthcare Corporation2008-05-21Not applicableUS flag
CyclophosphamideCapsule50 mg/1OralCipla USA Inc.2019-01-18Not applicableUS flag
CyclophosphamideInjection, powder, for solution2 g/100mLIntravenous; OralBluePoint Laboratories2020-10-19Not applicableUS flag
CyclophosphamideInjection, powder, for solution1 g/50mLIntravenous; OralNorthStar Rx LLC2019-01-08Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

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

    Learn more
  • Product Code
    Product Code

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

    Learn more
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Procytox for Injection 2000mg Pws IVCyclophosphamide (2 g) + Sodium chloride (900 mg)Powder, for solutionIntravenousCarter Horner Corp.1994-12-312001-05-22Canada flag

Categories

ATC Codes
L01AA01 — Cyclophosphamide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as nitrogen mustard compounds. These are compounds having two beta-haloalkyl groups bound to a nitrogen atom.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Nitrogen mustard compounds
Direct Parent
Nitrogen mustard compounds
Alternative Parents
Phosphoric monoester diamides / Oxazaphosphinanes / Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives / Alkyl chlorides
Substituents
Aliphatic heteromonocyclic compound / Alkyl chloride / Alkyl halide / Azacycle / Hydrocarbon derivative / Nitrogen mustard / Organic oxide / Organic oxygen compound / Organic phosphoric acid amide / Organic phosphoric acid derivative
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
organochlorine compound, nitrogen mustard, phosphorodiamide (CHEBI:4027)

Chemical Identifiers

UNII
6UXW23996M
CAS number
50-18-0
InChI Key
CMSMOCZEIVJLDB-UHFFFAOYSA-N
InChI
InChI=1S/C7H15Cl2N2O2P/c8-2-5-11(6-3-9)14(12)10-4-1-7-13-14/h1-7H2,(H,10,12)
IUPAC Name
2-[bis(2-chloroethyl)amino]-1,3,2λ⁵-oxazaphosphinan-2-one
SMILES
ClCCN(CCCl)P1(=O)NCCCO1

References

Synthesis Reference

Riccardo Dalla-Favera, Alessandro Massimo Gianni, "Retroviral vector capable of transducing the aldehyde dehydrogenase-1 gene and making cells resistant to the chemotherapeutic agent cyclophosphamide and its derivatives and analogs." U.S. Patent US6268138, issued March, 1999.

US6268138
General References
  1. Brock N: The history of the oxazaphosphorine cytostatics. Cancer. 1996 Aug 1;78(3):542-7. [PubMed:8697402]
  2. Brock N: Oxazaphosphorine cytostatics: past-present-future. Seventh Cain Memorial Award lecture. Cancer Res. 1989 Jan 1;49(1):1-7. [PubMed:2491747]
Human Metabolome Database
HMDB0014672
KEGG Drug
D07760
KEGG Compound
C07888
PubChem Compound
2907
PubChem Substance
46505441
ChemSpider
2804
BindingDB
50237604
RxNav
1545988
ChEBI
4027
ChEMBL
CHEMBL88
Therapeutic Targets Database
DAP000532
PharmGKB
PA449165
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Cyclophosphamide
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
MSDS
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentAdvanced Follicular Lymphoma1
4Active Not RecruitingTreatmentBreast Cancer1
4Active Not RecruitingTreatmentIgA Nephropathy1
4Active Not RecruitingTreatmentMalignant Lymphomas1
4CompletedHealth Services ResearchBreast Cancer1
4CompletedOtherBMI >30 kg/m2 / Breast Cancer1
4CompletedPreventionHematopoietic Stem Cell Transplantation (HSCT)1
4CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)5
4CompletedTreatmentAdult Acute Lymphocytic Leukemia4
4CompletedTreatmentAllergic granulomatous angiitis / Churg-Strauss Syndrome / Granulomatosis With Polyangiitis / Microscopic Polyangiitis / Polyarteritis Nodosa / Vasculitis1

Pharmacoeconomics

Manufacturers
  • Baxter healthcare corp
  • Baxter healthcare corp anesthesia and critical care
  • Teva parenteral medicines inc
  • Roxane laboratories inc
Packagers
  • Baxter International Inc.
  • Bristol-Myers Squibb Co.
  • Kaiser Foundation Hospital
  • Mead Johnson and Co.
  • Meda AB
  • Medisca Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmacia Inc.
  • Roxane Labs
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous200 mg
Injection, solutionIntravenous500 mg
Injection, powder, for solutionIntravenous1000 mg
Injection, powder, lyophilized, for solutionIntravenous1000 mg
Injection, powder, for solutionIntravenous1 g
Injection, powder, for solutionIntravenous200 mg
PowderIntravenous1 g
PowderIntravenous200 mg
Injection, powder, for solutionParenteral1 g
Injection, powder, for solutionParenteral2 g
Injection, powder, for solutionParenteral500 mg
Injection, powder, for solutionParenteral1000 mg
Injection, powder, for solutionParenteral2000 mg
CapsuleOral25 mg/1
CapsuleOral50 mg/1
Injection, powder, for solutionIntravenous; Oral1 g/50mL
Injection, powder, for solutionIntravenous; Oral2 g/100mL
Injection, powder, for solutionIntravenous; Oral500 mg/25mL
Injection, powder, lyophilized, for solutionIntravenous; Oral1 g/50mL
Injection, powder, lyophilized, for solutionIntravenous; Oral2 g/100mL
Injection, powder, lyophilized, for solutionIntravenous; Oral500 mg/25mL
Injection, solutionIntravenous200 mg/1mL
Injection, powder, for solution100 mg
Tablet50 mg
Injection, powder, for solutionIntramuscular; Intraperitoneal; Intrapleural; Intravascular1 g/50mL
Injection, powder, for solutionIntramuscular; Intraperitoneal; Intrapleural; Intravascular2 g/100mL
Injection, powder, for solutionIntramuscular; Intraperitoneal; Intrapleural; Intravascular500 mg/25mL
TabletOral25 mg/1
TabletOral50 mg/1
Injection, powder, for solution
Tablet, sugar coatedOral50 mg
Injection, powder, for solutionParenteral200 mg
Tablet, coatedOral50 mg
Injection, solutionIntravenous1 g
Tablet, film coated50 mg
Injection, powder, for solution1 G
Injection, powder, for solution200 MG
Injection, powder, for solution500 MG
Injection, powder, lyophilized, for solutionIntravenous200 mg
Injection, powder, for solutionIntravenous500 mg
Powder, for solutionIntravenous
Powder, for solutionIntravenous
Powder, for solutionParenteral
TabletOral
Prices
Unit descriptionCostUnit
Cyclophosphamide 500 mg vial37.76USD vial
Cyclophosphamide 100% powder33.66USD g
Cytoxan 500 mg vial15.25USD vial
Cytoxan 50 mg tablet4.14USD tablet
Cyclophosphamide 50 mg tablet3.92USD tablet
Cytoxan 25 mg tablet2.26USD tablet
Cyclophosphamide 25 mg tablet2.09USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)48-49Arnold, H., Brock, N. and Bourseaux, F.; U S . Patent 3,018,302; January 23,1962; assigned to Asta-Werke A.G. Chemische Fabrik (W. Germany).
water solubilitySoluble. 1-5 g/100 mL at 23 °CNot Available
logP0.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility15.1 mg/mLALOGPS
logP0.76ALOGPS
logP0.097ChemAxon
logS-1.2ALOGPS
pKa (Strongest Acidic)12.78ChemAxon
pKa (Strongest Basic)-0.57ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area41.57 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity58.48 m3·mol-1ChemAxon
Polarizability23.72 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9722
Blood Brain Barrier+0.971
Caco-2 permeable-0.5451
P-glycoprotein substrateNon-substrate0.71
P-glycoprotein inhibitor INon-inhibitor0.779
P-glycoprotein inhibitor IINon-inhibitor0.9797
Renal organic cation transporterNon-inhibitor0.8125
CYP450 2C9 substrateNon-substrate0.7856
CYP450 2D6 substrateNon-substrate0.5884
CYP450 3A4 substrateSubstrate0.5461
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9232
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9232
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9737
Ames testAMES toxic0.9146
CarcinogenicityNon-carcinogens0.8727
BiodegradationNot ready biodegradable0.9511
Rat acute toxicity3.3855 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.8419
hERG inhibition (predictor II)Non-inhibitor0.8735
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
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Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-08fr-9470000000-53f4a8ff83c415492e03
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/MSsplash10-001l-0970000000-939110a705ed71803ab8
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0090000000-2bdfe4296c2bdf8d4a99
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0190000000-1e8e017f8e39fa5d73cf
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0930000000-d7459c8d20a8fc59f6f0
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-33cb20e845200f9d2618
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-2900000000-09d33a8387b9d152f24a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-01ox-6900000000-cdebe09ff6df7c25b477
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0090000000-d749f27c3144da2c431c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0190000000-a6fa921df18384671a7c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0930000000-abdb40162fc8a44200f7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-8c0705ee62a5f9c7d44e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-2900000000-a299026342c77e92c48c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-01ox-6900000000-fc2845c75bbccc83ad99
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001l-0970000000-83e0f5b88b6fbe0a1ea7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-5490a2b493bfde967fa3
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-456626f46e480e0ac670
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-e3ecee739b09050e915a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-4cb33bb833e6cab9a106
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-0390000000-66983035d1db7ac36bd6
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0059-1490000000-36d8ebdb421248c38c7b
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-1390000000-b8dc1a824ec33e388213
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Targets

Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Cross-linking/alkylation
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Khan O, Middleton MR: The therapeutic potential of O6-alkylguanine DNA alkyltransferase inhibitors. Expert Opin Investig Drugs. 2007 Oct;16(10):1573-84. [PubMed:17922622]
  4. Schmidt E, Tony HP, Brocker EB, Kneitz C: Sun-induced life-threatening lupus nephritis. Ann N Y Acad Sci. 2007 Jun;1108:35-40. [PubMed:17893968]
  5. Zhang QH, Wu CF, Duan L, Yang JY: Protective effects of total saponins from stem and leaf of Panax ginseng against cyclophosphamide-induced genotoxicity and apoptosis in mouse bone marrow cells and peripheral lymphocyte cells. Food Chem Toxicol. 2008 Jan;46(1):293-302. Epub 2007 Aug 23. [PubMed:17904265]
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
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Cyclophosphamide FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. 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]
  2. Yang L, Yan C, Zhang F, Jiang B, Gao S, Liang Y, Huang L, Chen W: Effects of ketoconazole on cyclophosphamide metabolism: evaluation of CYP3A4 inhibition effect using the in vitro and in vivo models. Exp Anim. 2018 Feb 9;67(1):71-82. doi: 10.1538/expanim.17-0048. Epub 2017 Nov 13. [PubMed:29129847]
  3. Lindley C, Hamilton G, McCune JS, Faucette S, Shord SS, Hawke RL, Wang H, Gilbert D, Jolley S, Yan B, LeCluyse EL: The effect of cyclophosphamide with and without dexamethasone on cytochrome P450 3A4 and 2B6 in human hepatocytes. Drug Metab Dispos. 2002 Jul;30(7):814-22. doi: 10.1124/dmd.30.7.814. [PubMed:12065440]
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
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. 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]
  2. 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]
  3. Xie HJ, Yasar U, Lundgren S, Griskevicius L, Terelius Y, Hassan M, Rane A: Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation. Pharmacogenomics J. 2003;3(1):53-61. doi: 10.1038/sj.tpj.6500157. [PubMed:12629583]
  4. Wang H, Tompkins LM: CYP2B6: new insights into a historically overlooked cytochrome P450 isozyme. Curr Drug Metab. 2008 Sep;9(7):598-610. [PubMed:18781911]
  5. Lindley C, Hamilton G, McCune JS, Faucette S, Shord SS, Hawke RL, Wang H, Gilbert D, Jolley S, Yan B, LeCluyse EL: The effect of cyclophosphamide with and without dexamethasone on cytochrome P450 3A4 and 2B6 in human hepatocytes. Drug Metab Dispos. 2002 Jul;30(7):814-22. doi: 10.1124/dmd.30.7.814. [PubMed:12065440]
  6. Flockhart Table of Drug Interactions [Link]
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. Ren S, Yang JS, Kalhorn TF, Slattery JT: Oxidation of cyclophosphamide to 4-hydroxycyclophosphamide and deschloroethylcyclophosphamide in human liver microsomes. Cancer Res. 1997 Oct 1;57(19):4229-35. [PubMed:9331082]
  2. Helsby NA, Hui CY, Goldthorpe MA, Coller JK, Soh MC, Gow PJ, De Zoysa JZ, Tingle MD: The combined impact of CYP2C19 and CYP2B6 pharmacogenetics on cyclophosphamide bioactivation. Br J Clin Pharmacol. 2010 Dec;70(6):844-53. doi: 10.1111/j.1365-2125.2010.03789.x. [PubMed:21175440]
  3. Helsby NA, Lo WY, Sharples K, Riley G, Murray M, Spells K, Dzhelai M, Simpson A, Findlay M: CYP2C19 pharmacogenetics in advanced cancer: compromised function independent of genotype. Br J Cancer. 2008 Oct 21;99(8):1251-5. doi: 10.1038/sj.bjc.6604699. [PubMed:18854824]
  4. Flockhart Table of Drug Interactions [Link]
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. 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
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]
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. 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]
  2. Chang TK, Weber GF, Crespi CL, Waxman DJ: Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes. Cancer Res. 1993 Dec 1;53(23):5629-37. [PubMed:8242617]
  3. Chang TK, Yu L, Maurel P, Waxman DJ: Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: response to cytochrome P-450 inducers and autoinduction by oxazaphosphorines. Cancer Res. 1997 May 15;57(10):1946-54. [PubMed:9157990]
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. Ekhart C, Doodeman VD, Rodenhuis S, Smits PH, Beijnen JH, Huitema AD: Influence of polymorphisms of drug metabolizing enzymes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, GSTA1, GSTP1, ALDH1A1 and ALDH3A1) on the pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide. Pharmacogenet Genomics. 2008 Jun;18(6):515-23. doi: 10.1097/FPC.0b013e3282fc9766. [PubMed:18496131]

Drug created on June 13, 2005 07:24 / Updated on October 25, 2020 09:16

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