| Description | Furamidine is also a selective and cell-permeable protein arginine methyltransferase 1 (PRMT1) inhibitor with an IC50 of 9.4 μM. Furamidine is selective for PRMT1 over PRMT5, PRMT6, and PRMT4 (CARM1) (IC50s of 166 μM, 283 μM, and >400 μM, respectively). Furamidine (DB75) is abisbenzamidine derivative and an antiparasite agent. Furamidine is a potent, reversible and competitive tyrosyl-DNA phosphodiesterase 1 (TDP-1) inhibitor. Inhibition of TDP-1 by Furamidine is effective both with single- and double-stranded DNA substrates but is slightly stronger with the duplex DNA. |
| In vitro | Furamidine binds duplex DNA in the DNA minor groove selectively at AT rich sites.?Furamidine can also intercalate between GC base pairs of duplex DNA.?Furamidine could therefore interfere with DNA processing enzymes such as TDP-1.Furamidine (; 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 (; 20 μM; 15 hours; 293T cells) treatment significantly reduces the expression level of the methylated GFP-ALY protein in 293T cells. |
| In vivo | 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. |
| Target activity | PRMT5:166 µM (IC50), PRMT1:9.4 μM (IC50), PRMT4:>400 µM (IC50), PRMT6:283 µM (IC50) |
| Synonyms | DB75, NSC 305831 |
| molecular weight | 304.35 |
| Molecular formula | C18H16N4O |
| CAS | 73819-26-8 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| References | 1. Antony S, et al. Novel high-throughput electrochemiluminescent assay for identification of human tyrosyl-DNA phosphodiesterase (Tdp1) inhibitors and characterization of furamidine (NSC 305831) as an inhibitor of Tdp1. Nucleic Acids Res. 2007;35(13):4474-84. 2. Yan L, et al. Diamidine compounds for selective inhibition of protein arginine methyltransferase 1. J Med Chem. 2014 Mar 27;57(6):2611-22. 3. Keil A, et al. The Topoisomerase I Inhibitor Irinotecan and the Tyrosyl-DNA Phosphodiesterase 1 Inhibitor Furamidine Synergistically Suppress Murine Lupus Nephritis. Arthritis Rheumatol. 2015 Jul;67(7):1858-67. |