Phosphoramide mustard

Names

[ Name ]:
Phosphoramide mustard

[Synonym ]:
Phosphamide mustard
Friedman acid
Phosphorodiamidic mustard
Phosphoramide mustard
amino-[bis(2-chloroethyl)amino]phosphinic acid
Phosphorsaeure-amid-[bis-(2-chlor-aethyl)-amid]
N,N-Bis(2-chloroethyl)phosphorodiamidic acid
N,N-Bis-(2-chlor-aethyl)-diamidophosphorsaeure
N,N-bis-(2-chloro-ethyl)-diamidophosphoric acid
NLPD
ASTA 5317
N-Lost-phosphorsaeurediamid [German]

Biological Activity

[Description]:

Phosphoramide mustard is the major metabolite for Cyclophosphamide (HY-17420), with anticancer activitiy. Phosphoramide mustard induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response[1][2].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA Alkylator/Crosslinker

[Target]

DNA Alkylator[1]

[In Vitro]

Phosphoramide mustard causes cytotoxicity through forming cross-linked DNA adducts which inhibit DNA strand separation during replication[1]. Phosphoramide mustard destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage[1]. Phosphoramide mustard (3-6 μM; 48 hours) reduces cell viability in rat spontaneously immortalized granulosa cells (SIGCs)[1]. Phosphoramide mustard (3-6 μM; 24-48 hours) induces DNA adduct formation[1]. Phosphoramide mustard (3-6 μM; 24-48 hours) induces ovarian DNA damage in rat ovaries[1]. Phosphoramide mustard increases DNA damage responses (DDR) gene (Atm, Parp1, Prkdc, Xrcc6, Brca1, Rad51) mRNA expression level[1]. Phosphoramide mustard (3-6 μM; 24-48 hours) increased DDR proteins[1]. Cell Viability Assay[1] Cell Line: SIGCs Concentration: 0.5 μM, 1 μM, 3 μM, 6 μM Incubation Time: 48 hours Result: Reduced cell viability at concentrations of 3 μM and higher. RT-PCR[1] Cell Line: SIGCs Concentration: 3 μM, 6 μM Incubation Time: 24 hours, 48 hours Result: Increased DDR gene mRNA expression levels. Western Blot Analysis[1] Cell Line: SIGCs Concentration: 3 μM, 6 μM Incubation Time: 24 hours, 48 hours Result: Generally increased DDR proteins.

[In Vivo]

Phosphoramide mustard (2.1-20.7 mg/kg; i.p.; daily; for 5 days) inhibits subcutaneous tumor growth in rats[2]. Phosphoramide mustard (59.4 mg/kg; i.v.) has a plasma disappearance half-life of 15.1 minutes[2]. Animal Model: Rat, subcutaneously implanted Walker 256 carcinosarcoma tumor[2] Dosage: 2.1 mg/kg, 4.8 mg/kg, 10.4 mg/kg, 20.7 mg/kg Administration: Intraperitoneal injection, once daily, for 5 consecutive days Result: Required to produce 50% inhibition of subcutaneous tumor growth with dose of 12 mg/kg. Animal Model: Rats[2] Dosage: 59.4 mg/kg (Pharmacokinetic Analysis) Administration: Intravenous injection Result: Has a disappearance half-life of 15.1 minutes in plasma.

[References]

[1]. Shanthi Ganesan, et al. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells. Toxicol Appl Pharmacol. 2015 Feb 1; 282(3): 252–258.

[2]. S Genka, et al. Brain and plasma pharmacokinetics and anticancer activities of cyclophosphamide and phosphoramide mustard in the rat. Cancer Chemother Pharmacol. 1990;27(1):1-7.

Chemical & Physical Properties

[ Density]:
1.474g/cm3

[ Boiling Point ]:
363.5ºC at 760mmHg

[ Molecular Formula ]:
C₄H₁₁Cl₂N₂O₂P

[ Molecular Weight ]:
221.02200

[ Flash Point ]:
173.6ºC

[ Exact Mass ]:
219.99400

[ PSA ]:
76.37000

[ LogP ]:
1.52540

[ Vapour Pressure ]:
2.84E-06mmHg at 25°C

[ Index of Refraction ]:
1.525

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds

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