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73819-26-8

中文名稱 4,4'-(2,5-Furandiyl)bis(benzenecarboximidamide)
CAS 73819-26-8
分子式 C18H16N4O
分子量 304.35
MOL 文件 73819-26-8.mol
73819-26-8 結(jié)構(gòu)式 73819-26-8 結(jié)構(gòu)式

基本信息

中文別名
呋喃脒
英文別名
NSC 305831
NSC 305831-d8
FuraMidine-d8
2,5-Bis(4-guanylphenyl)furan
2,5-bis(4-amidinophenyl)furan
2,5-Bis(4-guanylphenyl)furan-d8
2,5-Bis(4-aMidinophenyl)furan-d8
4,4'-(2,5-Furandiyl)bis(benzenecarboximidamide)
Benzenecarboximidamide, 4,4'-(2,5-furandiyl)bis-
4-[5-(4-carbamimidoylphenyl)furan-2-yl]benzenecarboximidamide

常見問題列表

生物活性
Furamidine (DB75) 是一種選擇性的且細(xì)胞可滲透的蛋白精氨酸甲基轉(zhuǎn)移酶 1 (PRMT1) 抑制劑,IC50 為 9.4 μM。Furamidine 對(duì) PRMT1 的選擇性高于 PRMT5,PRMT6 和 PRMT4 (CARM1) (IC50 分別為 166 μM,283 μM 和 >400 μM)。Furamidine 是一種有效的,可逆的和競(jìng)爭(zhēng)性的酪氨酰 DNA 磷酸二酯酶 1 (TDP-1) 抑制劑。Furamidine 對(duì) TDP-1 的抑制作用對(duì)單鏈和雙鏈 DNA 底物均有效,對(duì)雙鏈 DNA 的作用更強(qiáng)。Furamidine 也是一種抗寄生蟲劑。
靶點(diǎn)

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)

體外研究

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.
體內(nèi)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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