Furamidine

Furamidine (DB75) is a selective 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 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. Furamidine is also an antiparasite agent.

Product information

CAS Number: 73819-26-8

Molecular Weight: 304.35

Formula: C18H16N4O

Synonym:

DB75

NSC 305831

Chemical Name: 4-[5-(4-carbamimidoylphenyl)furan-2-yl]benzene-1-carboximidamide

Smiles: NC(=N)C1C=CC(=CC=1)C1=CC=C(O1)C1C=CC(=CC=1)C(N)=N

InChiKey: ZJHZBDRZEZEDGB-UHFFFAOYSA-N

InChi: InChI=1S/C18H16N4O/c19-17(20)13-5-1-11(2-6-13)15-9-10-16(23-15)12-3-7-14(8-4-12)18(21)22/h1-10H,(H3,19,20)(H3,21,22)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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. 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.

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.

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.

Products are for research use only. Not for human use.