[CAS NO. 55368-40-6] Furamidine dihydrochloride
PRODUCTS SPECIFICATIONS [55368-40-6]
DESCRIPTION [55368-40-6]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 377.27 |
| Molecular Formula | C18H18Cl2N4O |
| SMILES | N=C(C1=CC=C(C2=CC=C(C3=CC=C(C(N)=N)C=C3)O2)C=C1)N.[H]Cl.[H]Cl |
1 Publications Citing Use of MCE
Summary
Furamidine dihydrochloride (DB75 dihydrochloride) is a selective protein arginine methyltransferase 1 (PRMT1) inhibitor with an IC 50 of 9.4 μM. Furamidine dihydrochloride is selective for PRMT1 over PRMT5 , PRMT6 , and PRMT4 (CARM1) (IC 50 s of 166 µM, 283 µM, and >400 µM, respectively). Furamidine dihydrochloride is a potent, reversible and competitive tyrosyl-DNA phosphodiesterase 1 (TDP-1) inhibitor. Inhibition of TDP-1 by Furamidine dihydrochloride is effective both with single- and double-stranded DNA substrates but is slightly stronger with the duplex DNA. Furamidine dihydrochloride is also an antiparasite agent [1] [2] [3] .
IC50 & Target
|
PRMT1 |
In Vitro
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
[1]
.
Furamidine (compound 1; 20 μM; 15 hours; 293T cells) treatment significantly reduces the expression level of the methylated GFP-ALY protein in 293T cells
[1]
.
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
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay [1]
| 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 [1]
| Cell Line: | 293T cells |
| Concentration: | 20 μM |
| Incubation Time: | 15 hours |
| Result: | The expression level of the methylated GFP-ALY protein is significantly reduced. |
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 [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Female NZB/NZW mice (6-week-old) with Irinotecan (1 mg/kg) [3] |
| 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
-20°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 12.5 mg/mL ( 33.13 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.6506 mL | 13.2531 mL | 26.5062 mL |
| 5 mM | 0.5301 mL | 2.6506 mL | 5.3012 mL |
| 10 mM | 0.2651 mL | 1.3253 mL | 2.6506 mL |
-
1.
-
2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 1.25 mg/mL (3.31 mM); Clear solution
References
- [1] Yan L, et al. Diamidine compounds for selective inhibition of protein arginine methyltransferase 1. J Med Chem. 2014 Mar 27;57(6):2611-22.
- [2] 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.
- [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.