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55368-40-6

中文名称 呋喃脒二盐酸盐
英文名称 Furamidine dihydrochloride
CAS 55368-40-6
分子式 C18H16N4O
MOL 文件 55368-40-6.mol
更新日期 2023/03/20 15:41:17
55368-40-6 结构式 55368-40-6 结构式

基本信息

中文别名
呋喃脒二盐酸盐
英文别名
DB75
DB-75
WR-199385
Furamidine
FuraMidine Dihydrochloride
Furamidine (hydrochloride)
Furamidine dihydrochloride >=98% (HPLC)
2,5-Furandiylbis(1,4-phenylene)bisformamidine
4-[5-(4-carbamimidoylphenyl)-2-furyl]benzenecarboximidamide
4,4'-(2,5-Furandiyl)bis-benzenecarboximidamide dihydrochloride
所属类别
生物化工:抑制剂

物理化学性质

熔点400-401 °C(Solv: ethanol (64-17-5))
储存条件-20°C
溶解度可溶于DMSO(少许)、甲醇(少许)
形态粉末
颜色白色至米色
稳定性感光

常见问题列表

生物活性
Furamidine dihydrochloride (DB75 dihydrochloride) 是一种选择性的且细胞可渗透的蛋白精氨酸甲基转移酶 1 (PRMT1) 抑制剂,IC50 为 9.4 μM。Furamidine dihydrochloride 对 PRMT1 的选择性高于 PRMT5,PRMT6 和 PRMT4 (CARM1) (IC50 分别为 166 µM,283 µM 和 >400 µM)。Furamidine dihydrochloride 是一种有效的,可逆的和竞争性的酪氨酰 DNA 磷酸二酯酶 1 (TDP-1) 抑制剂。Furamidine dihydrochloride 对 TDP-1 的抑制作用对单链和双链 DNA 底物均有效,对双链 DNA 的作用更强。Furamidine dihydrochloride 也是一种抗寄生虫剂。
靶点

IC50: 9.4 μM (Protein arginine methyltransferase 1 (PRMT1)); 166 µM (PRMT5), 283 µM (PRMT6) and >400 µM (PRMT4)
Parasite
Tyrosyl-DNA phosphodiesterase 1 (TDP-1)

体外研究

Furamidine (compound 1; 20 μM; 72 hours; leukemia cell lines) inhibits cell growth for most of the leukemia cell lines except HEL cells which have JAK2V617F mutations.
Furamidine (compound 1; 20 μM; 15 hours; 293T cells) treatment significantly reduces the expression level of the methylated GFP-ALY protein in 293T cells.
Furamidine binds duplex DNA in the DNA minor groove selectively at AT rich sites [(A/T)4]. Furamidine can also intercalate between GC base pairs of duplex DNA. Furamidine could therefore interfere with DNA processing enzymes such as TDP-1.

Cell Viability Assay

Cell Line: Meg-01, K562, HL-60, NB4, MOLM13, HEL, CMK, CMY, CMS and CHRF cells
Concentration: 20 μM
Incubation Time: 72 hours
Result: Inhibited cell growth for most of the leukemia cell lines except HEL cells which have JAK2V617F mutations.

Western Blot Analysis

Cell Line: 293T cells
Concentration: 20 μM
Incubation Time: 15 hours
Result: The expression level of the methylated GFP-ALY protein is significantly reduced.
体内研究

Furamidine (1 mg/kg; intraperitoneal injection; 3 times a week and repeated every 4 weeks; for 34 weeks; female NZB/NZW mice) and Irinotecan combined treatment suppresses proteinuria and prolongs survival of lupus-prone NZB/NZW mice. The combination treatment does not change the levels of anti-dsDNA antibodies.

Animal Model: Female NZB/NZW mice (6-week-old) with Irinotecan (1 mg/kg)
Dosage: 1 mg/kg
Administration: Intraperitoneal injection; 3 times a week and repeated every 4 weeks; for 34 weeks
Result: Suppressed proteinuria and prolongs survival of lupus-prone NZB/NZW mice combined with Irinotecan.
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