PERFOSFAMIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C7H15Cl2N2O4P
Molecular Weight	293.085
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OO[C@@H]1CCO[P@](=O)(N1)N(CCCl)CCCl

InChI

InChIKey=VPAWVRUHMJVRHU-VGDKGRGNSA-N

InChI=1S/C7H15Cl2N2O4P/c8-2-4-11(5-3-9)16(13)10-7(15-12)1-6-14-16/h7,12H,1-6H2,(H,10,13)/t7-,16-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://adisinsight.springer.com/drugs/800001660 | https://www.cancer.gov/publications/dictionaries/cancer-drug/def/perfosfamide | https://www.ncbi.nlm.nih.gov/pubmed/12060130 | https://www.ncbi.nlm.nih.gov/pubmed/6214268

Perfosfamide is the active metabolite of the nitrogen mustard cyclophosphamide with potent antineoplastic and immunosuppressive properties. Perfosfamide alkylates DNA, thereby inhibiting DNA replication and RNA and protein synthesis. The incubation of normal human marrow cells with perfosfamide has a toxic effect on granulocyte-macrophage progenitor cells that is dose as well as white blood cell concentration dependent. It is likely that this dependency of the perfosfamide stem cell effect is caused not only by the target white blood cell concentration but by the suspension’s total protein concentration. Autologous bone marrow transplantation with perfosfamide purging in patients with acute myeloid leukemia in second complete remission produced results similar to that reported with allogeneic bone marrow transplantation. Perfosfamide had been in phase III clinical trial for the treatment of acute myeloid leukemia. However, this development was discontinued.

Originator

Approval Year

PubMed

Title	Date	PubMed
Studies on the urotoxicity of oxazaphosphorine cytostatics and its prevention--I. Experimental studies on the urotoxicity of alkylating compounds.	1981 Jun	7308258
Immediate hypersensitivity reaction to cyclophosphamide.	1994 Jul	8024619
De novo expression of transfected human class 1 aldehyde dehydrogenase (ALDH) causes resistance to oxazaphosphorine anti-cancer alkylating agents in hamster V79 cell lines. Elevated class 1 ALDH activity is closely correlated with reduction in DNA interstrand cross-linking and lethality.	1996 May 17	8662658
Cyclophosphamide enhances TNF-alpha-induced apoptotic cell death in murine vascular endothelial cell.	2006 Mar 6	16488414
Teratogen-induced activation of p53 in early postimplantation mouse embryos.	2007 Jan	17068108
RNAi-mediated knockdown of aldehyde dehydrogenase class-1A1 and class-3A1 is specific and reveals that each contributes equally to the resistance against 4-hydroperoxycyclophosphamide.	2007 Jan	16614850
Cyclophosphamide-induced apoptosis in COV434 human granulosa cells involves oxidative stress and glutathione depletion.	2007 Jul	17434952
4-hydroperoxy-cyclophosphamide mediates caspase-independent T-cell apoptosis involving oxidative stress-induced nuclear relocation of mitochondrial apoptogenic factors AIF and EndoG.	2008 Feb	18034189
The gene expression profiles of medulloblastoma cell lines resistant to preactivated cyclophosphamide.	2008 May	18473730
Teratogen responsive signaling pathways in organogenesis stage mouse limbs.	2009 Apr	19429390
Effects of exposure to a DNA damaging agent on the hypoxia inducible factors in organogenesis stage mouse limbs.	2012	23251655
The enzymatic activity of human aldehyde dehydrogenases 1A2 and 2 (ALDH1A2 and ALDH2) is detected by Aldefluor, inhibited by diethylaminobenzaldehyde and has significant effects on cell proliferation and drug resistance.	2012 Jan 5	22079344

Patents

Name

Type

Language

PERFOSFAMIDE

Official Name

English

4-HC

Code

English

PERGAMID

Brand Name

English

(±)-CIS-2-(BIS(2-CHLOROETHYL)AMINO)TETRAHYDRO-2H-1,3,2-OXAZAPHOSPHORIN-4-YL HYDROPEROXIDE, P-OXIDE

Common Name

English

NSC-181815

Code

English

perfosfamide [INN]

Common Name

English

2H-1,3,2-OXAZAPHOSPHORIN-2-AMINE, N,N-BIS(2-CHLOROETHYL)TETRAHYDRO-4-HYDROPEROXY-, 2-OXIDE, (2R,4R)-REL-

Common Name

English

PERFOSFAMIDE [MI]

Common Name

English

HYDROPEROXIDE, 2-(BIS(2-CHLOROETHYL)AMINO)TETRAHYDRO-2H-1,3,2-OXAZAPHOSPHORIN-4-YL, P-OXIDE, CIS-(±)-

Common Name

English

4-HYDROPEROXYCYCLOPHOSPHAMIDE

Common Name

English

PERFOSFAMIDE [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C697