PALIFOSFAMIDE

Investigational

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 282 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 83

Conditions

Condition	Modality	Targets	Highest Phase	Product
Small-cell lung cancer 41 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28605291	Primary		Phase III 665	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 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
44.7 μg/mL EXPERIMENT https://doi.org/10.1200/jco.2006.24.18_suppl.9524	595 mg/m² 1 times / day multiple, intravenous dose: 595 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		PALIFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1.68 mg × min/mL EXPERIMENT https://doi.org/10.1200/jco.2006.24.18_suppl.9524	595 mg/m² 1 times / day multiple, intravenous dose: 595 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		PALIFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
35 min EXPERIMENT https://doi.org/10.1200/jco.2006.24.18_suppl.9524	595 mg/m² 1 times / day multiple, intravenous dose: 595 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		PALIFOSFAMIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15592722/	unknown		PALIFOSFAMIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: 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
eMolecules	50282999	https://orderbb.emolecules.com/search/#?query=50282999
Enamine	BBV-40209294	http://www.enaminestore.com/catalog/BBV-40209294
eNovation Chemicals	D556885	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D556885&searchbtn.x=0&searchbtn.y=0
Hairui	GLSA03305	http://www.hairuichem.com/en/product/search.do?q=GLSA03305
Lab Network	LN01342006	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342006
mcule	MCULE-4010500360	https://mcule.com/MCULE-4010500360/
MedChem Express	HY-14798	https://www.medchemexpress.com/search.html?q=HY-14798&ft=&fa=&fp=
Molnova	M17476	https://www.molnova.com/en/serch-list.html?keywords=M17476
MolPort	MolPort-005-942-381	https://www.molport.com/shop/molecule-link/MolPort-005-942-381
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

PubMed

Title	Date	PubMed
The fate of new fosfamides in phase III studies in advanced soft tissue sarcoma.	2017-10	28841543
Carboplatin and Etoposide With or Without Palifosfamide in Untreated Extensive-Stage Small-Cell Lung Cancer: A Multicenter, Adaptive, Randomized Phase III Study (MATISSE).	2017-08-10	28605291
PICASSO III: A Phase III, Placebo-Controlled Study of Doxorubicin With or Without Palifosfamide in Patients With Metastatic Soft Tissue Sarcoma.	2016-11-10	27621408
Anticancer activity of stabilized palifosfamide in vivo: schedule effects, oral bioavailability, and enhanced activity with docetaxel and doxorubicin.	2012-02	22027537
Palifosfamide, a bifunctional alkylator for the treatment of sarcomas.	2010-01	20024846
Preclinical activity of palifosfamide lysine (ZIO-201) in pediatric sarcomas including oxazaphosphorine-resistant osteosarcoma.	2009-09	19224214
Phosphate prodrugs of isophosphoramide mustard.	2003-09-19	13678316

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

NSC-297900

Preferred 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

Classification Tree Code System Code

NCI_THESAURUS

C697