4-HYDROXYCYCLOPHOSPHAMIDE

Details

Stereochemistry	MIXED
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)(N1)N(CCCl)CCCl

InChI

InChIKey=RANONBLIHMVXAJ-UHFFFAOYSA-N

InChI=1S/C7H15Cl2N2O3P/c8-2-4-11(5-3-9)15(13)10-7(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: http://www.myelomabeacon.com/resources/2008/10/15/cyclophosphamide/

Cyclophosphamide (the generic name for Cytoxan, Neosar, Revimmune), also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group. It is used to treat various types of cancer and some autoimmune disorders. It is a "prodrug"; it is converted in the liver to active forms that have chemotherapeutic activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 282 Target ID: CHEMBL2311221 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Crosslinking Agent 83

Conditions

Condition	Modality	Highest Phase	Product
Hodgkin’s disease, lymphocytic lymphoma (nodular or diffuse) 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960
Multiple myeloma 159 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960
Chronic lymphocytic leukemia 59 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960
Mycosis fungoides 31 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960
Neuroblastoma 26 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960
Adenocarcinoma of the ovary 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960
Retinoblastoma 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960
Breast cancer 432 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960
Minimal change nephrotic syndrome 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960
Hodgkin’s disease mixed-cell type lymphoma 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960
Hodgkin’s disease histiocytic lymphoma 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960
Burkitt’s lymphoma 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960
Chronic granulocytic leukemia 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960
Acute myelogenous and monocytic leukemia 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960
Acute lymphoblastic leukemia 27 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Primary	Approved 8583	CYTOXAN Approved Use To treat Hodgkin’s disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt’s lymphoma; multiple myeloma, leukemias, mycosis fungoides, neuroblastoma, adenocarcinoma of ovary, retinoblastoma, breast carcinoma and minimal Change Nephrotic Syndrome in Pediatric Patients. Launch Date 1960

C_max

Value	Dose	Co-administered	Analyte	Population
30.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22245954/	600 mg/m² single, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		CYCLOPHOSPHAMIDE ANHYDROUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
31.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22245954/	600 mg/m² single, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: DOXORUBICIN	DOXORUBICIN	CYCLOPHOSPHAMIDE ANHYDROUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1234 μg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24022191	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		CYCLOPHOSPHAMIDE ANHYDROUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
317 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22245954/	600 mg/m² single, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		CYCLOPHOSPHAMIDE ANHYDROUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
247 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22245954/	600 mg/m² single, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: DOXORUBICIN	DOXORUBICIN	CYCLOPHOSPHAMIDE ANHYDROUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
17588 μg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24022191	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		CYCLOPHOSPHAMIDE ANHYDROUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.29 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22245954/	600 mg/m² single, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		CYCLOPHOSPHAMIDE ANHYDROUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.07 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22245954/	600 mg/m² single, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: DOXORUBICIN	DOXORUBICIN	CYCLOPHOSPHAMIDE ANHYDROUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.93 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/497087/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		CYCLOPHOSPHAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
10.8 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24022191	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		CYCLOPHOSPHAMIDE ANHYDROUS plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
80% DRUG LABEL https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/0e1cb955-99c8-4fe5-89d1-399c8e52174e/spl-doc?hl=cyclophosphamide			CYCLOPHOSPHAMIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
200 mg/m2 2 times / day multiple, intravenous MTD Dose: 200 mg/m2, 2 times / day Route: intravenous Route: multiple Dose: 200 mg/m2, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24440659	unhealthy, 21-72 Health Status: unhealthy Age Group: 21-72 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/24440659	Other AEs: Bilirubin total increased, Diarrhea... Other AEs: Bilirubin total increased (grade 3, 20%) Diarrhea (grade 3, 20%) Sources: https://pubmed.ncbi.nlm.nih.gov/24440659
300 mg/m2 2 times / day multiple, intravenous Studied dose Dose: 300 mg/m2, 2 times / day Route: intravenous Route: multiple Dose: 300 mg/m2, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24440659	unhealthy, 21-72 Health Status: unhealthy Age Group: 21-72 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/24440659	DLT: Diarrhea, Lipase increased... Dose limiting toxicities: Diarrhea (grade 3-5, 12%) Lipase increased (grade 4, 4%) Transaminases increased (grade 3-5, 12%) Nausea and vomiting (grade 3-5, 4%) Sources: https://pubmed.ncbi.nlm.nih.gov/24440659
3300 mg/m2 single, intravenous Highest studied dose Dose: 3300 mg/m2 Route: intravenous Route: single Dose: 3300 mg/m2 Sources: https://pubmed.ncbi.nlm.nih.gov/8558227	unhealthy, 26-64 Health Status: unhealthy Age Group: 26-64 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/8558227	DLT: Neutropenia, Thrombocytopenia... Dose limiting toxicities: Neutropenia (grade 4, 33.3%) Thrombocytopenia (16.7%) Neutropenia (16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/8558227
2700 mg/m2 single, intravenous MTD Dose: 2700 mg/m2 Route: intravenous Route: single Dose: 2700 mg/m2 Sources: https://pubmed.ncbi.nlm.nih.gov/8558227	unhealthy, 26-64 Health Status: unhealthy Age Group: 26-64 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/8558227	DLT: Neutropenia, Thrombocytopenia... Dose limiting toxicities: Neutropenia (grade 4, 16.7%) Thrombocytopenia (16.7%) Neutropenia (16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/8558227
2000 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 2000 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 2000 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/9296218	unhealthy, 27 - 70 Health Status: unhealthy Age Group: 27 - 70 Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/9296218	DLT: Febrile neutropenia, Thrombocytopenia... Dose limiting toxicities: Febrile neutropenia (33.3%) Thrombocytopenia (grade 4, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/9296218
100 mg 1 times / day multiple, oral Highest studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19117344	unhealthy, 47-78 Health Status: unhealthy Age Group: 47-78 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19117344	DLT: Neutropenia, Thrombocytopenia... Dose limiting toxicities: Neutropenia (grade 4, 33.3%) Thrombocytopenia (grade 4, 16.7%) Constipation (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/19117344
50 mg 1 times / day multiple, oral MTD Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19117344	unhealthy, 47-78 Health Status: unhealthy Age Group: 47-78 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/19117344	Sources: https://pubmed.ncbi.nlm.nih.gov/19117344
5 mg/kg 1 times / day multiple, oral Recommended Dose: 5 mg/kg, 1 times / day Route: oral Route: multiple Dose: 5 mg/kg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Disc. AE: Myelosuppression, Immunosuppression... AEs leading to discontinuation/dose reduction: Myelosuppression Immunosuppression Bone marrow failure Infection Urinary tract toxicity Toxicity renal Cystitis hemorrhagic Pyelitis Ureteritis Hematuria Cardiotoxicity Myocarditis Myopericarditis Pericardial effusion Arrhythmia (NOS) Congestive heart failure Pulmonary toxicity Pneumonitis Pulmonary fibrosis Pulmonary veno-occlusive disease Respiratory failure Metastases Venoocclusive liver disease Fetal damage Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf
50 mg/kg multiple, intravenous Recommended Dose: 50 mg/kg Route: intravenous Route: multiple Dose: 50 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf	Disc. AE: Myelosuppression, Immunosuppression... AEs leading to discontinuation/dose reduction: Myelosuppression Immunosuppression Bone marrow failure Infection Urinary tract toxicity Toxicity renal Cystitis hemorrhagic Pyelitis Ureteritis Hematuria Cardiotoxicity Myocarditis Myopericarditis Pericardial effusion Arrhythmia (NOS) Congestive heart failure Pulmonary toxicity Pneumonitis Pulmonary fibrosis Pulmonary veno-occlusive disease Respiratory failure Metastases Venoocclusive liver disease Fetal damage Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
activator 150 substrate 1946 inducer 1087	activator 23 inducer 440

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
		CYP2B6 669

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C9 2497	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/12739762/	no
CYP2A6 911	activator 342 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP2B6 1160	activator 342 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP2B6 1160	inducer 1966 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3588594/	yes
CYP2C18 13	activator 342 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP2C19 2141	activator 342 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP2C9 2497	activator 342 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP3A4 2633	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/12739762/	yes
CYP3A5 201	activator 342 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15 Page: 15.0	yes
CYP3A4 2633	activator 342 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814316/ Page: 15.0	yes	weak (co-administration study) Comment: coadministration with ketoconazole: had small effect on CYCLOPHOSPHAMIDE plasma concentration Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/012141s090,012142s112lbl.pdf#page=15; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814316/ Page: 15.0

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814316/	yes	DECP 3	yes (co-administration study) Comment: coadministration with ketoconazole: caused a KTZ dose-dependent decrease in main parameters of DECP (Cmax, Tmax, and AUC0–∞) and provided magnitude exposure of DECP (more than a 50% AUC decrease) as a consequence of CYP3A inhibition Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814316/

PubMed

Title	Date	PubMed
Dominant role of intercellular adhesion molecule-1 in the pathogenesis of autoimmune diabetes in non-obese diabetic mice.	2001-09	11591119
Prevention of further cyclophosphamide induced hemorrhagic cystitis by hyperbaric oxygen and mesna in guinea pigs.	2001-09	11490309
Doxorubicin and taxane combination regimens for metastatic breast cancer: focus on cardiac effects.	2001-08	11552226
Serum cardiac troponin I levels and ECG/Echo monitoring in breast cancer patients undergoing high-dose (7 g/m(2)) cyclophosphamide.	2001-08	11535996
What is proper treatment for Wegener granulomatosis?	2001-07-23	11485512
Involvement of hypogastric and pelvic nerves for conveying cystitis induced nociception in conscious rats.	2001-07	11435893
Bladder carcinoma associated with cyclophosphamide therapy for ovarian cancer occurring with a latency of 20 years.	2001-07	11426986
High-dose paclitaxel in combination with doxorubicin, cyclophosphamide and peripheral blood progenitor cell rescue in patients with high-risk primary and responding metastatic breast carcinoma: toxicity profile, relationship to paclitaxel pharmacokinetics and short-term outcome.	2001-06-15	11401310
Frequent, moderate-dose cyclophosphamide administration improves the efficacy of cytochrome P-450/cytochrome P-450 reductase-based cancer gene therapy.	2001-06-01	11389073
Leiomyosarcoma of the bladder fourteen years after cyclophosphamide therapy for retinoblastoma.	2001-06	11487082
Transitional cell carcinoma of the urinary bladder following exposure to cyclophosphamide in childhood.	2001-06	11475121
Establishment of the transformants expressing human cytochrome P450 subtypes in HepG2, and their applications on drug metabolism and toxicology.	2001-06	11377097
Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage-colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized mice.	2001-05-01	11325840
Contribution of alveolar phagocytes to antibiotic efficacy in an experimental lung infection with Streptococcus pneumoniae.	2001-05	11545565
Protective effect of berberine on cyclophosphamide-induced haemorrhagic cystitis in rats.	2001-05	11393582
Expression of inducible nitric oxide synthase in primary culture of rat bladder smooth muscle cells by plasma from cyclophosphamide-treated rats.	2001-03-23	11282106
Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.	2001-03-15	11248153
Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer.	2001-03-01	11230490
Treatment based on a combination of the CYP2B1/cyclophosphamide system and p53 delivery enhances tumour regression in human pancreatic cancer.	2001-03	11332152
Alterations in neuropeptide expression in lumbosacral bladder pathways following chronic cystitis.	2001-03	11312054
Nitric oxide synthases and cyclophosphamide-induced cystitis in rats.	2001-03	11284451
Hematopoietic stem cell transplantation for high-risk adult patients with severe aplastic anemia; reduction of graft failure by enhancing stem cell dose.	2001-03	11255278
Erythropoietin restores the anemia-induced reduction in cyclophosphamide cytotoxicity in rat tumors.	2001-02-15	11245434
Intraneoplastic polymer-based delivery of cyclophosphamide for intratumoral bioconversion by a replicating oncolytic viral vector.	2001-02-01	11221871
Transient posterior encephalopathy induced by chemotherapy in children.	2001-02	11275465
Azathioprine-induced destructive cholangitis.	2001-02	11232733
Cyclophosphamide-induced hemorrhagic cystitis in rats that underwent colocystoplasty: experimental study.	2001-02	11176454
Hypersensitivity reactions to carboplatin administration are common but not always severe: a 10-year experience.	2001	11528251
Report of severe neurotoxicity with cyclophosphamide.	2000-12-29	11132226
Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma.	2000-12-15	11135211
Paternal exposure to cyclophosphamide induces DNA damage and alters the expression of DNA repair genes in the rat preimplantation embryo.	2000-11-09	11056294
[Assessment of cardiotoxicity of high dose cyclophosphamide with electrocardiographic, echocardiographic, and troponin I monitoring in patients with breast tumors].	2000-11	11109196
Nitric oxide and NK(1)-tachykinin receptors in cyclophosphamide-induced cystitis, in rats.	2000-11	11046124
Fatal haemorrhagic myocarditis secondary to cyclophosphamide therapy.	2000-10	11271907
A comparative study of sequential priming and mobilisation of progenitor cells with rhG-CSF alone and high-dose cyclophosphamide plus rhG-CSF.	2000-10	11042651
Cytochrome P-450 2C9 sensitizes human prostate tumor cells to cyclophosphamide via a bystander effect.	2000-10	10991840
Mixed chimerism, heart, and skin allograft tolerance in cyclophosphamide-induced tolerance.	2000-09-27	11014644
Myopericarditis caused by cyclophosphamide used to mobilize peripheral blood stem cells in a myeloma patient with renal failure.	2000-09	11041571
Bilateral blindness and lumbosacral myelopathy associated with high-dose carmustine and cisplatin therapy.	2000-09	11020424
Individualizing high-dose oral busulfan: prospective dose adjustment in a pediatric population undergoing allogeneic stem cell transplantation for advanced hematologic malignancies.	2000-09	11019834
GST-pi gene-transduced hematopoietic progenitor cell transplantation overcomes the bone marrow toxicity of cyclophosphamide in mice.	2000-08-10	10954901
Regulation of cyclophosphamide-induced eosinophilia in contact sensitivity: functional roles of interleukin-5-producing CD4(+) lymphocytes.	2000-08-01	11006010
Cyclophosphamide inhibits the development of diabetes in the diabetes-prone BB rat.	2000-08	10990075
Limits to the "benefits" from our oncologic interventions: a case report.	2000-08	10926815
Invasive bladder cancer after cyclophosphamide administration for nephrotic syndrome--a case report.	2000-06	10920579
Quantitative prediction of catalepsy induced by amoxapine, cinnarizine and cyclophosphamide in mice.	2000-05	11180191
[Apoptosis of B lymphocytic leukemia induced by anticancer drugs and their cell cycle specificity].	1998-01	10921050
Carcinoma of the urinary bladder in patients receiving cyclophosphamide.	1975-08-07	1138180
Cyclophosphamide in exacerbations of multiple sclerosis. Therapeutic trial and a strategy for pilot drug studies.	1975-06	1097604
Remission of active chronic hepatitis after treatment with cyclophosphamide and prednisolone. Report of four cases.	1975-02	1144250

Patents

Sample Use Guides

In Vivo Use Guide

40-50 mg per kg in divided doses over 2 to 5 days in malignant diseases and 2 mg per kg daily for 8 to 12 weeks in minimal change nephrotic sindrome

Route of Administration: Intravenous

In Vitro Use Guide

from 20 to 160 ug/ml

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:37:19 GMT 2025` Edited by `admin` on `Mon Mar 31 22:37:19 GMT 2025`
Record UNII	1XBF4E50HS
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

NSC-196562

Preferred Name

English

4-HYDROXYCYCLOPHOSPHAMIDE

Common Name

English

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

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID90960669