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Details

Stereochemistry ABSOLUTE
Molecular Formula C10H21Cl2N2O7P
Molecular Weight 383.163
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GLUFOSFAMIDE

SMILES

OC[C@H]1O[C@@H](OP(=O)(NCCCl)NCCCl)[C@H](O)[C@@H](O)[C@@H]1O

InChI

InChIKey=PSVUJBVBCOISSP-SPFKKGSWSA-N
InChI=1S/C10H21Cl2N2O7P/c11-1-3-13-22(19,14-4-2-12)21-10-9(18)8(17)7(16)6(5-15)20-10/h6-10,15-18H,1-5H2,(H2,13,14,19)/t6-,7-,8+,9-,10+/m1/s1

HIDE SMILES / InChI

Molecular Formula C10H21Cl2N2O7P
Molecular Weight 383.163
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Glufosamide (glucosylifosfamide mustars) consists of iphosphoramide mustard conjugated to glucose, and is an alkylating agent (affecting the ability of the cancer cell to multiply by causing breakage of the DNA strands). Glufosamide is considered a targeted chemotherapy with fewer side effects than alternative chemotherapies. Its specific mode of action on normal and pathological cells is still under investigation. Glufosamide was studied for use in several cancers, like pancreatic and prostate cancer, and head and neck squamous cell carcinoma. Multipe clinical trials have been completed or are still ongoing. Most promising results were found when glufosamide was used in combination treatments, rather than alone.

CNS Activity

Curator's Comment: Ifosfamide crosses the blood-brain barrier and may cause encephalopathy.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
IFEX

Approved Use

Ifosfamide injection, used in combination with certain other approved antineoplastic agents, is indicated for third line chemotherapy of germ cell testicular cancer. It should be used in combination with a prophylactic agent for hemorrhagic cystitis, such as mesna.

Launch Date

1988
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
200 μM
1.5 g/m² single, oral
dose: 1.5 g/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
203 μM
1.5 g/m² single, intravenous
dose: 1.5 g/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1360 μM × h
1.5 g/m² single, oral
dose: 1.5 g/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1520 μM × h
1.5 g/m² single, intravenous
dose: 1.5 g/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
7.54 mM × h
3 g/m² 1 times / day multiple, intravenous
dose: 3 g/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5 h
1.5 g/m² single, oral
dose: 1.5 g/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5.6 h
1.5 g/m² single, intravenous
dose: 1.5 g/m²
route of administration: Intravenous
experiment type: SINGLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.12 h
3 g/m² 1 times / day multiple, intravenous
dose: 3 g/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
IFOSFAMIDE blood
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
100%
IFOSFAMIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
18 g/m2 1 times / day multiple, intravenous (total)
MTD
Dose: 18 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 18 g/m2, 1 times / day
Sources: Page: p.1090
unhealthy, 45
n = 6
Health Status: unhealthy
Condition: Sarcoma
Age Group: 45
Sex: M+F
Population Size: 6
Sources: Page: p.1090
DLT: Neutropenia, Infection...
Dose limiting toxicities:
Neutropenia (grade 4, 83.3%)
Infection (severe, 33.3%)
Thrombocytopenia (grade 4, 66.7%)
Sources: Page: p.1090
2.25 g/m2 1 times / day multiple, intravenous
MTD
Dose: 2.25 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 2.25 g/m2, 1 times / day
Co-administed with::
doxorubicin, i.v(45 mg/m2)
Sources: Page: p.6
unhealthy, 45
n = 3
Health Status: unhealthy
Condition: Breast cancer
Age Group: 45
Sex: F
Population Size: 3
Sources: Page: p.6
DLT: Neutropenia, Febrile neutropenia...
Dose limiting toxicities:
Neutropenia (grade 4, 66.7%)
Febrile neutropenia (grade 5, 33.3%)
Thrombocytopenia (grade 4, 66.7%)
Anemia (grade 4, 66.7%)
Sources: Page: p.6
1.2 g/m2 1 times / day multiple, intravenous
Recommended
Dose: 1.2 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 1.2 g/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Testicular cancer
Sources: Page: p.1
Disc. AE: Nephrotoxicity, Renal failure...
AEs leading to
discontinuation/dose reduction:
Nephrotoxicity (severe)
Renal failure (severe)
Cystitis hemorrhagic (severe)
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Thrombocytopenia grade 4, 66.7%
DLT
18 g/m2 1 times / day multiple, intravenous (total)
MTD
Dose: 18 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 18 g/m2, 1 times / day
Sources: Page: p.1090
unhealthy, 45
n = 6
Health Status: unhealthy
Condition: Sarcoma
Age Group: 45
Sex: M+F
Population Size: 6
Sources: Page: p.1090
Neutropenia grade 4, 83.3%
DLT
18 g/m2 1 times / day multiple, intravenous (total)
MTD
Dose: 18 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 18 g/m2, 1 times / day
Sources: Page: p.1090
unhealthy, 45
n = 6
Health Status: unhealthy
Condition: Sarcoma
Age Group: 45
Sex: M+F
Population Size: 6
Sources: Page: p.1090
Infection severe, 33.3%
DLT
18 g/m2 1 times / day multiple, intravenous (total)
MTD
Dose: 18 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 18 g/m2, 1 times / day
Sources: Page: p.1090
unhealthy, 45
n = 6
Health Status: unhealthy
Condition: Sarcoma
Age Group: 45
Sex: M+F
Population Size: 6
Sources: Page: p.1090
Anemia grade 4, 66.7%
DLT
2.25 g/m2 1 times / day multiple, intravenous
MTD
Dose: 2.25 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 2.25 g/m2, 1 times / day
Co-administed with::
doxorubicin, i.v(45 mg/m2)
Sources: Page: p.6
unhealthy, 45
n = 3
Health Status: unhealthy
Condition: Breast cancer
Age Group: 45
Sex: F
Population Size: 3
Sources: Page: p.6
Neutropenia grade 4, 66.7%
DLT
2.25 g/m2 1 times / day multiple, intravenous
MTD
Dose: 2.25 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 2.25 g/m2, 1 times / day
Co-administed with::
doxorubicin, i.v(45 mg/m2)
Sources: Page: p.6
unhealthy, 45
n = 3
Health Status: unhealthy
Condition: Breast cancer
Age Group: 45
Sex: F
Population Size: 3
Sources: Page: p.6
Thrombocytopenia grade 4, 66.7%
DLT
2.25 g/m2 1 times / day multiple, intravenous
MTD
Dose: 2.25 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 2.25 g/m2, 1 times / day
Co-administed with::
doxorubicin, i.v(45 mg/m2)
Sources: Page: p.6
unhealthy, 45
n = 3
Health Status: unhealthy
Condition: Breast cancer
Age Group: 45
Sex: F
Population Size: 3
Sources: Page: p.6
Febrile neutropenia grade 5, 33.3%
DLT, Disc. AE
2.25 g/m2 1 times / day multiple, intravenous
MTD
Dose: 2.25 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 2.25 g/m2, 1 times / day
Co-administed with::
doxorubicin, i.v(45 mg/m2)
Sources: Page: p.6
unhealthy, 45
n = 3
Health Status: unhealthy
Condition: Breast cancer
Age Group: 45
Sex: F
Population Size: 3
Sources: Page: p.6
Cystitis hemorrhagic severe
Disc. AE
1.2 g/m2 1 times / day multiple, intravenous
Recommended
Dose: 1.2 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 1.2 g/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Testicular cancer
Sources: Page: p.1
Nephrotoxicity severe
Disc. AE
1.2 g/m2 1 times / day multiple, intravenous
Recommended
Dose: 1.2 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 1.2 g/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Testicular cancer
Sources: Page: p.1
Renal failure severe
Disc. AE
1.2 g/m2 1 times / day multiple, intravenous
Recommended
Dose: 1.2 g/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 1.2 g/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Testicular cancer
Sources: Page: p.1
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
poor
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
no (co-administration study)
Comment: Coadministration of ifosfamide with ketoconazole or rifampin did not produce changes inthe pharmacokinetics of the parent or metabolites that may result in an increased benefit of ifosfamidetherapy. (https://pubmed.ncbi.nlm.nih.gov/11503007/)
Page: 28.0
yes
no (co-administration study)
Comment: Coadministration of ifosfamide with ketoconazole or rifampin did not produce changes inthe pharmacokinetics of the parent or metabolites that may result in an increased benefit of ifosfamidetherapy. (https://pubmed.ncbi.nlm.nih.gov/11503007/)
Page: 28.0
PubMed

PubMed

TitleDatePubMed
Prospective evaluation of high-dose ifosfamide-related nephrotoxicity in young adult patients with recurrent osteosarcoma previously treated with cisplatin, methotrexate and standard-dose ifosfamide.
1999 Jan
L-Histidinol attenuates Fanconi syndrome induced by ifosfamide in rats.
1999 Jul-Aug
Injection of encapsulated cells producing an ifosfamide-activating cytochrome P450 for targeted chemotherapy to pancreatic tumors.
1999 Jun 30
Characterization of a human cell clone expressing cytochrome P450 for safe use in human somatic cell therapy.
1999 Jun 30
Preresectional chemotherapy in stage IIIA non-small-cell lung cancer: a 7-year assessment of a randomized controlled trial.
1999 Oct
Methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: report of 12 cases and a review of the literature.
2000 Jan
Subacute central nervous system degeneration in a child: an unusual manifestation of ifosfamide intoxication.
2000 Jul
Distinctive potentiating effects of cisplatin and/or ifosfamide combined with etoposide in human small cell lung carcinoma xenografts.
2000 May
Paclitaxel by 72-hour continuous infusion followed by bolus intravenous ifosfamide or epirubicin: results of two phase I studies.
2001
Comparison of double and triple high-dose chemotherapy with autologous blood stem cell transplantation in patients with metastatic breast cancer.
2001
Salvage chemotherapy in relapsed germ cell tumors.
2001 Apr
A three-drug regimen (gemcitabine, ifosfamide and cisplatin) for advanced non-small-cell lung cancer.
2001 Apr
Local hyperthermia, radiation, and chemotherapy in recurrent breast cancer is feasible and effective except for inflammatory disease.
2001 Apr 1
Phase II study of paclitaxel, ifosfamide, and carboplatin in patients with recurrent or metastatic head and neck squamous cell carcinoma.
2001 Apr 1
Chemotherapy agents in transitional cell carcinoma: the old and the new.
2001 Feb
PBPC mobilization with paclitaxel, ifosfamide, and G-CSF with or without amifostine: results of a prospective randomized trial.
2001 Feb
A comparison of methods of loco-regional chemotherapy combined with systemic chemotherapy as neo-adjuvant treatment of osteosarcoma of the extremity.
2001 Feb
Neoadjuvant chemotherapy for high grade osteosarcoma of the extremities: long-term results for patients treated according to the Rizzoli IOR/OS-3b protocol.
2001 Feb
How effective is dose-intensive/myeloablative therapy against Ewing's sarcoma/primitive neuroectodermal tumor metastatic to bone or bone marrow? The Memorial Sloan-Kettering experience and a literature review.
2001 Feb 1
Clinical pharmacokinetics and pharmacodynamics of ifosfamide and its metabolites.
2001 Jan
Anticancer drug-induced kidney disorders.
2001 Jan
Recurrent germinoma in the optic nerve: report of two cases.
2001 Jan
Docetaxel and ifosfamide as second line treatment for patients with advanced or metastatic urothelial cancer after failure of platinum chemotherapy: a phase 2 study.
2001 Jan
Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children's Research Hospital OS-91 trial.
2001 Jan 1
Phase II study of paclitaxel, ifosfamide, and cisplatin as second-line treatment in relapsed small-cell lung cancer.
2001 Jan 1
Salvage treatment with paclitaxel, ifosfamide, and cisplatin plus high-dose carboplatin, etoposide, and thiotepa followed by autologous stem-cell rescue in patients with relapsed or refractory germ cell cancer.
2001 Jan 1
Optimal duration of preoperative therapy in unilateral and nonmetastatic Wilms' tumor in children older than 6 months: results of the Ninth International Society of Pediatric Oncology Wilms' Tumor Trial and Study.
2001 Jan 15
A randomized trial of amifostine as a cytoprotective agent in patients receiving chemotherapy for small cell lung cancer.
2001 Jan 5
A randomised phase II study on neo-adjuvant chemotherapy for 'high-risk' adult soft-tissue sarcoma.
2001 Jun
Necrotic, rather than apoptotic, cell death caused by cytochrome P450-activated ifosfamide.
2001 Mar
Intrasellar rhabdomyosarcoma: case report.
2001 Mar
[A case of primary malignant hemangiopericytoma of the lung with marked response to combination chemotherapy with cisplatin, ifosfamide and gemcitabine].
2001 Mar
Phase I trial of ifosfamide and 24-h infusional paclitaxel in pelvic malignancies: a Gynecologic Oncology Group study.
2001 Mar
Localized Ewing tumor of bone: final results of the cooperative Ewing's Sarcoma Study CESS 86.
2001 Mar 15
Tumor oxygenation after radiotherapy, chemotherapy, and/or hyperthermia predicts tumor free survival.
2001 Mar 15
Topoisomerase IIalpha and other drug resistance markers in advanced non-small cell lung cancer.
2001 May
Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin, cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation: Children's Cancer Group Study CCG-5912.
2001 May 1
A novel alkylating agent, glufosfamide, enhances the activity of gemcitabine in vitro and in vivo.
2007 Aug
Patents

Sample Use Guides

30-min infusion at a dose of 1.2 grams per m2 per day for 5 consecutive days
Route of Administration: Intravenous
Human testicular germ cell tumour lines H 12.1 and 2102 EP were treated with ifosfamide at 50 mg kg-1 day-1.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:38:53 GMT 2023
Edited
by admin
on Fri Dec 15 15:38:53 GMT 2023
Record UNII
1W5N8SZD9A
Record Status Validated (UNII)
Record Version
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Name Type Language
GLUFOSFAMIDE
HSDB   INN   MART.   MI   WHO-DD  
INN  
Official Name English
D-19575
Code English
D19575
Code English
GLUCOSYLIFOSFAMIDE MUSTARD
Common Name English
GLUFOSFAMIDE [HSDB]
Common Name English
GLUFOSFAMIDE [MI]
Common Name English
GLUFOSFAMIDE [MART.]
Common Name English
glufosfamide [INN]
Common Name English
.BETA.-D-GLUCOPYRANOSE, 1-(N,N'-BIS(2-CHLOROETHYL))PHOSPHORODIAMIDATE
Common Name English
Glufosfamide [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C697
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
EU-Orphan Drug EU/3/11/851
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
FDA ORPHAN DRUG 221606
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
Code System Code Type Description
MERCK INDEX
m5774
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
PRIMARY Merck Index
NCI_THESAURUS
C1612
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
PRIMARY
DRUG BANK
DB06177
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
PRIMARY
HSDB
7024
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
PRIMARY
ChEMBL
CHEMBL2107143
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
PRIMARY
FDA UNII
1W5N8SZD9A
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
PRIMARY
EVMPD
SUB07941MIG
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
PRIMARY
SMS_ID
100000084228
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
PRIMARY
EPA CompTox
DTXSID001031222
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
PRIMARY
WIKIPEDIA
Glufosfamide
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
PRIMARY
INN
7590
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
PRIMARY
CAS
132682-98-5
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
PRIMARY
PUBCHEM
123628
Created by admin on Fri Dec 15 15:38:53 GMT 2023 , Edited by admin on Fri Dec 15 15:38:53 GMT 2023
PRIMARY
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