磷酰胺氮芥

生物活性靶点体外研究体内研究

磷酰胺氮芥

CAS号:10159-53-2
英文名:phosphoramide mustard
中文名:磷酰胺氮芥
CBNumber:CB01386806
分子式:C4H11Cl2N2O2P
分子量:221.02
MOL File:10159-53-2.mol

磷酰胺氮芥化学性质

熔点 :115 °C
沸点 :363.5±52.0 °C(Predicted)
密度 :1.474±0.06 g/cm3(Predicted)
酸度系数(pKa) :0.41±0.50(Predicted)

安全信息

毒性 :LD50 intraperitoneal in mouse: 184mg/kg

磷酰胺氮芥性质、用途与生产工艺

生物活性 Phosphoramide mustard 是环磷酰胺 (HY-17420) 的活性代谢物，具有抗肿瘤活性。Phosphoramide mustard 能诱导 DNA 损伤。
靶点

DNA Alkylator

体外研究

Phosphoramide mustard causes cytotoxicity through forming cross-linked DNA adducts which inhibit DNA strand separation during replication.
Phosphoramide mustard (3-6 μM; 48 hours) reduces cell viability in rat spontaneously immortalized granulosa cells (SIGCs).
Phosphoramide mustard (3-6 μM; 24-48 hours) induces DNA adduct formation and ovarian DNA damage.
Phosphoramide mustard (3-6 μM; 24-48 hours) increases DNA damage responses (DDR) gene mRNA expression levels and DDR proteins.

Cell Viability Assay

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

Cell Line:	SIGCs
Concentration:	3 μM, 6 μM
Incubation Time:	24 hours, 48 hours
Result:	Increased DDR gene mRNA expression levels.

Western Blot Analysis

Cell Line:	SIGCs
Concentration:	3 μM, 6 μM
Incubation Time:	24 hours, 48 hours
Result:	Generally increased DDR proteins.

体内研究

Phosphoramide mustard (2.1-20.7 mg/kg; i.p.; daily; for 5 days) inhibits subcutaneous tumor growth in rats.
Phosphoramide mustard exhibits terminal elimination half-lives (rat 15.1 min) following intravenous administration (rat 59.4 mg/kg).

Animal Model:	Rat, subcutaneously implanted Walker 256 carcinosarcoma tumor
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.