4,4'-(2,5-Furandiyl)bis(benzenecarboximidamide)
4,4'-(2,5-Furandiyl)bis(benzenecarboximidamide) 用途与合成方法
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)
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. |
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. |
