PALIFOSFAMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C4H11Cl2N2O2P
Molecular Weight	221.022
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OP(=O)(NCCCl)NCCCl

InChI

InChIKey=BKCJZNIZRWYHBN-UHFFFAOYSA-N

InChI=1S/C4H11Cl2N2O2P/c5-1-3-7-11(9,10)8-4-2-6/h1-4H2,(H3,7,8,9,10)

HIDE SMILES / InChI

Description
Sources: http://cancerres.aacrjournals.org/content/67/9_Supplement/3200 | https://www.ncbi.nlm.nih.gov/pubmed/20024846 | http://www.ziopharm.com/pipeline/overview

Palifosfamide or ZIO-201 (isophosphoramide mustard; IPM), a bi-functional DNA alkylator, is the active metabolite of ifosfamide (IFOS). IFOS and the related drug cyclophosphamide (CPA) are widely used anti-cancer drugs. Both are pro-drugs and need to be metabolized to be active. Their clinical use is limited by the toxicity associated with some of their metabolites. Palifosfamide has shown efficacy in diverse cancer models. ZIOPHARM Oncology Inc, under license from Dekk-Tec Inc, was developing palifosfamide, a formulation of isophosphoramide mustard with tris(hydroxymethyl)aminomethane salt-stabilization (palifosfamide-tris) and previously with lysine-stabilization (palifosfamide-lys). Preclinical studies and phase I and I/II clinical trials demonstrated that palifosfamide-tris had an antitumor efficiency comparable or superior to that of ifosfamide. To date ZIO-201 is not present in ZIOPHARM pipeline.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 278 Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10647503 \| https://www.ncbi.nlm.nih.gov/pubmed/1554391 \| https://www.ncbi.nlm.nih.gov/pubmed/2754703	Crosslinking Agent 81

Conditions

Condition	Modality	Targets	Highest Phase	Product
Small-cell lung cancer 41 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28605291	Primary		Phase III 656	Unknown Approved Use Unknown
Soft tissue sarcoma 10 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27621408 https://www.ncbi.nlm.nih.gov/pubmed/28841543	Primary		Phase III 656	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00100B	https://www.1pchem.com/search?query=1P00100B
AChemBlock	O33942	http://www.achemblock.com/catalogsearch/result/?q=O33942
ApexBio Technology	A3696	https://www.apexbt.com/catalogsearch/result/?q=A3696
AstaTech	N16915	http://astatechinc.com/CPSResult.php?CRNO=N16915
BLD Pharm	BD141840	http://www.bldpharm.com/search/Search.html?keyword=BD141840
BOC Sciences	31645-39-3	http://www.bocsci.com/description.asp?cas=31645-39-3
Chem Scene	CS-1324	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1324
Chemspace	CSC010001499	https://chem-space.com/CSC010001499
Enamine	BBV-40209294	http://www.enaminestore.com/catalog/BBV-40209294
Hairui	GLSA03305	http://www.hairuichem.com/en/product/search.do?q=GLSA03305
Lab Network	LN01342006	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342006
MedChem Express	HY-14798	https://www.medchemexpress.com/search.html?q=HY-14798&ft=&fa=&fp=
MolPort	MolPort-005-942-381	https://www.molport.com/shop/molecule-link/MolPort-005-942-381
Molnova	M17476	https://www.molnova.com/en/serch-list.html?keywords=M17476
MuseChem	I003128	https://www.musechem.com/product/I003128.html
MuseChem	I008548	https://www.musechem.com/product/I008548.html
Selleck Chemicals	S5840	http://www.selleckchem.com/search.html?searchDTO.searchParam=S5840
ShangHai Biochempartner	BCP23687	http://www.biochempartner.com/search_BCP23687
TargetMol	T4350	https://www.targetmol.com/search?keyword=T4350
eMolecules	50282999	https://orderbb.emolecules.com/search/#?query=50282999
eNovation Chemicals	D556885	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D556885&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-4010500360	https://mcule.com/MCULE-4010500360/

PubMed

Title	Date	PubMed
Phosphate prodrugs of isophosphoramide mustard.	2003 Mar-Apr	13678316
Preclinical activity of palifosfamide lysine (ZIO-201) in pediatric sarcomas including oxazaphosphorine-resistant osteosarcoma.	2009 Sep	19224214
Palifosfamide, a bifunctional alkylator for the treatment of sarcomas.	2010 Jan	20024846
Anticancer activity of stabilized palifosfamide in vivo: schedule effects, oral bioavailability, and enhanced activity with docetaxel and doxorubicin.	2012 Feb	22027537
Carboplatin and Etoposide With or Without Palifosfamide in Untreated Extensive-Stage Small-Cell Lung Cancer: A Multicenter, Adaptive, Randomized Phase III Study (MATISSE).	2017 Aug 10	28605291

Patents

Sample Use Guides

In Vivo Use Guide

PICASSO III: A Phase III, Placebo-Controlled Study of Doxorubicin With or Without Palifosfamide in Patients With Metastatic Soft Tissue Sarcoma. Patients were randomly assigned 1:1 to receive doxorubicin 75 mg/m2 intravenously day 1 plus palifosfamide 150 mg/m2/d intravenously days 1 to 3 or doxorubicin plus placebo once every 21 days for up to six cycles. The primary end point was progression-free survival (PFS) by independent radiologic review.

Route of Administration: Intravenous

In Vitro Use Guide

Palifosfamide lysine was cytotoxic against all the osteosarcome cell lines tested with the IC(50) ranging from 0.5 to 1.5 microg/ml except for OS222, which had an IC(50) of 7 microg/ml.

Name

Type

Language

PALIFOSFAMIDE

Official Name

English

IFOSFAMIDE MUSTARD

Common Name

English

Palifosfamide [WHO-DD]

Common Name

English

PALIFOSFAMIDE [MART.]

Common Name

English

IPM

Code

English

palifosfamide [INN]

Common Name

English

ZIO-201

Code

English

PHOSPHORODIAMIDIC ACID, N,N'-BIS(2-CHLOROETHYL)-

Common Name

English

N,N'-BIS(2-CHLOROETHYL)PHOSPHORODIAMIDIC ACID

Systematic Name

English

ISOPHOSPHAMIDE MUSTARD

Common Name

English

PALIFOSFAMIDE [USAN]

Common Name

English

NSC-297900

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C697