氢溴酸卤夫酮

生物活性靶点体外研究体内研究氢溴酸卤夫酮试剂级价格

氢溴酸卤夫酮

CAS号:64924-67-0
英文名:Halofuginone hydrobromide
中文名:氢溴酸卤夫酮
CBNumber:CB91230111
分子式:C16H17BrClN3O3.HBr
分子量:495.59
MOL File:64924-67-0.mol

氢溴酸卤夫酮化学性质

熔点 :247° (dec)
储存条件 :Store at -20°C
溶解度 :Soluble to 100 mM in DMSO.
形态 :Solid
颜色 :White to off-white

安全信息

危险品标志 :Xn
危险类别码 :22
危险品运输编号 :UN2811 - class 6.1 - PG 1 - EHS - Toxic solids, organic, n.o.s., HI: all
WGK Germany :3
RTECS号 :VA2397066

氢溴酸卤夫酮性质、用途与生产工艺

生物活性 Halofuginone hydrobromide (RU-19110 hydrobromide) 是 Febrifugine 的一种低毒性衍生物，可从 Dichroa febrifuga 中分离出来。Halofuginone 是一种 ATP 竞争性的脯氨酰-tRNA 合成酶 (prolyl-tRNA synthetase) 抑制剂，Ki 为 18.3 nM。Halofuginone 是 I 型胶原 (type-I collagen) 合成的特异性抑制剂，并通过抑制 TGF-β 活性可减轻骨关节炎。
靶点

Ki: 18.3±0.5 nM (prolyl-tRNA synthetase)

体外研究

Halofuginone competitively inhibits prolyl-tRNA synthetase by occupying both the prolineand tRNA-binding pockets of prolyl-tRNA synthetase.
The IC ₅₀ s of Halofuginone (1, 10, 100, 1000, 10000 nM; 48 hours) are 114.6 and 58.9 nM in KYSE70 and A549 cells, respectively.
The IC ₅₀ s of Halofuginone (1, 10, 100, 1000 nM; 24 hours) for NRF2 protein are 22.3 and 37.2 nM in KYSE70 and A549 cells, respectively. The IC ₅₀ of Halofuginone for global protein synthesis is 22.6 and 45.7 nM in KYSE70 and A549 cells, respectively.

Cell Viability Assay

Cell Line:	KYSE70 cells from human oesophageal cancer harbouring a mutation in the NRF2 gene and A549 cells harbouring the KEAP1 gene mutation
Concentration:	1, 10, 100, 1000, 10000 nM
Incubation Time:	48 hours
Result:	The IC ₅₀ s were 114.6 and 58.9 nM in KYSE70 and A549 cells, respectively.

Western Blot Analysis

Cell Line:	KYSE70 cells from human oesophageal cancer harbouring a mutation in the NRF2 gene and A549 cells harbouring the KEAP1 gene mutation
Concentration:	1, 10, 100, 1000 nM
Incubation Time:	24 hours
Result:	The IC ₅₀ s for NRF2 protein were 22.3 and 37.2 nM in KYSE70 and A549 cells, respectively.

体内研究

Halofuginone (0.2, 0.5, 1 or 2.5 mg/kg; injected intraperitoneally every other day for 1 month) attenuates progression of OA in anterior cruciate ligament transection (ACLT) mice. Lower concentration (0.2 or 0.5 mg/kg) has minimal effects on subchondral bone and higher concentration (2.5 mg/kg) induces proteoglycan loss in articular cartilage.
Halofuginone (0.25 mg/kg; intraperitoneally injected; every day; 16 days) decreases NRF2 protein levels in tumors. While the tumor volumes do not change substantially between treatments with the vehicle, Halofuginone (0.25 mg/kg, intraperitoneally injected, every day) or cisplatin alone. Combined treatment with Halofuginone and Cisplatin significantly suppresses the tumor volume compared to treatment with Halofuginone or cisplatin alone.

Animal Model:	3-month-old male C57BL/6J (WT) mice
Dosage:	0.2, 0.5, 1 or 2.5 mg/kg
Administration:	Injected intraperitoneally every other day for 1 month
Result:	Attenuated progression of OA in ACLT mice.

Animal Model:	Male nude mice (BALB/C nu/nu mice) (6-8-week)
Dosage:	0.25 mg/kg
Administration:	Intraperitoneally injected; every day; 16 days
Result:	The combined treatment with Cisplatin significantly suppressed the tumor volume. NRF2 protein levels in tumors were indeed decreased.