(3E,5E)-3,5-双(4-硝基亚苄基)哌啶-4-酮

生物活性靶点体外研究体内研究 (3E,5E)-3,5-双(4-硝基亚苄基)哌啶-4-酮试剂级价格

CAS号:919091-63-7
英文名:RA-9
中文名:(3E,5E)-3,5-双(4-硝基亚苄基)哌啶-4-酮
CBNumber:CB16188329
分子式:C19H15N3O5
分子量:365.34
MOL File:919091-63-7.mol

(3E,5E)-3,5-双(4-硝基亚苄基)哌啶-4-酮化学性质

熔点 :230-233 °C(Solv: ethyl ether (60-29-7); acetonitrile (75-05-8))
沸点 :588.5±50.0 °C(Predicted)
密度 :1.414±0.06 g/cm3(Predicted)
储存条件 :Store at -20°C
溶解度 :DMSO: 4.17 mg/mL (11.41 mM; ultrasonic and warming and heat to 80°C)
酸度系数(pKa) :5.13±0.20(Predicted)
形态 :Solid
颜色 :Light yellow to yellow

(3E,5E)-3,5-双(4-硝基亚苄基)哌啶-4-酮性质、用途与生产工艺

生物活性 RA-9 是一种具有细胞渗透性的蛋白酶体相关的 deubiquitinating enzymes (DUBs) 的强效选择性抑制剂，具有良好的毒性和抗癌活性。RA-9 可在卵巢癌细胞系中选择性地诱导凋亡。
靶点
Target Value
DUBs
()

体外研究

RA-9 (10-30 μM; 48 hours) inhibits growth of ovarian cancer cell lines and primary cultures.
RA-9 (1.25-5 μM; 18 hours) causes cell cycle arrest and caspase-mediated apoptosis in ovarian cancer cells.
RA-9 (5 μM; 0-24 hours) induces ER-stress responses in ovarian cancer cells.
RA-9 (5 μM; over 24 hours) treatment results with time-dependent accumulation of the cleaved formed of PARP noticeable as early as 8 hours.

Cell Viability Assay

Cell Line:	Cisplatin-sensitive ovarian cancer cell lines TOV-21G and ES-2, Cisplatin-resistant ovarian cancer cell lines HEY and OVCAR-3, primary ovarian cancer cells
Concentration:	10, 20, 30 μM
Incubation Time:	48 hours
Result:	Compromised the viability of ovarian cancer cells in a dose-dependent fashion.

Cell Cycle Analysis

Cell Line:	ES-2 cells
Concentration:	1.25, 5 μM
Incubation Time:	18 hours
Result:	Resulted in a dose-dependent increase in the fraction of ES-2 cells in the G2-M cell cycle phase.

Western Blot Analysis

Cell Line:	ES-2, SKOV-3 and TOV-21G ovarian cancer cells
Concentration:	5 μM
Incubation Time:	0-24 h
Result:	Caused a time-dependent increase in the steady levels of the early ER-stress marker GRP-78, as well as the late ER-stress markers IRE1-α and Ero1L-α.

体内研究

RA-9 (5 mg/kg; i.p; one-day on, two-days off) inhibits human ovarian cancer cell growth in vivo and prolongs survival in a mouse model for ovarian cancer.

Animal Model:	Six-week-old female immunodeficient (NCr nu/nu) mice
Dosage:	5 mg/kg
Administration:	I.p; one-day on, two-days off
Result:	Significant reduction in tumor burden at day 12.