product name SGC707
Description: SGC707 is a potent, selective and cell-active allosteric inhibitor of protein arginine methyltransferase 3 (PRMT3) with IC50 and Kd of 31 nM and 53 nM, respectively. PRMT3 is one of the four type I protein arginine N-methyltransferases and has been implicated in ribosomal biosynthesis via catalyzing the formation of asymmetric (type I) mono- and dimethylarginine. PRMT3 has also been involved in cancer via interaction with the DAL-1 tumor suppressor protein [1]. SGC707 inhibits the activity of PRMT3 by targeting the dimerization interface of PRMT3.
References: Angew Chem Int Ed Engl. 2015 Apr 20;54(17):5166-70; Epigenomics. 2015;7(8):1327-38.
298.34
Formula
C16H18N4O2
CAS No.
1687736-54-4
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 59 mg/mL (197.7 mM)
Water: <1 mg/mL
Ethanol: 59 mg/mL (197.7 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: In cells, SGC707 binds to PRMT3 and reduces PRMT3-dependent H4R3me2a. SGC707 also stabilizes PRMT3 in both HEK293 and A549 cells with EC50 values of 1.3 μM and 1.6 μM, respectively. Kinase Assay: A radioactivity-based assay is optimized and used to determine the inhibition of PRMT3 in vitro. In a scintillation proximity assay (SPA), tritiated S-adenosylmethionine (3H-SAM) served as a methyl donor to methylate biotinylated histone peptide substrate. After completion of the reaction, the reaction mixture is transferred to the wells of a streptavidin / scintillant-coated microplate. The Biotinylated peptides binding to streptavidin coated resin, brings the incorporated 3H-methyl and the scintillant to close proximity. The amount of methylated peptide is quantified by tracing the radioactivity (counts per minute) as measured by the TopCount NXT™ Microplate Scintillation and Luminescence Counter. Due to the very acidic nature of the 3H-SAM solution, non-tritiated (cold) SAM is used to supplement the reactions. The C-terminally biotinylated peptide composed of the first 24 amino acids residues of histone H4 (H4 1-24) is used as substrate. The typical assay mixture contained 0.01% Tween-20, 5 mM DTT, 20 nM PRMT3, 0.3 µM B-H4 1-24 and 28 µM (5 µM 3H-SAM plus 23 µM cold SAM) SAM in 20 mM Tris-HCl (pH 7.5) and a final volume of 20 µL. The IC50 values are determined at Km concentrations of both substrates by titration of the compound in the reaction mixture in a range between 2000-0.2 nM. Cell Assay: Cells (LnCap, U2O s, HFF, MCF-7, and MDA-MB-231 cells) are seeded in 96-well plates and treated with different concentrations of SGC707 for 72 h. Cell viability is determined using Alamar blue 0.01 mg/mL in the media. Resazurin reduction is monitored with 544 nm excitation, measuring fluorescence at 590 nm. |
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| In Vivo | In CD-1 male mice, SGC707 (30 mg/kg, i.p.) gives good plasma exposure over 6 h with the peak plasma level of 38000 nM, which suggests that SGC707 is suitable for animal studies |
| Animal model | |
| Formulation & Dosage | |
| References | Angew Chem Int Ed Engl. 2015 Apr 20;54(17):5166-70; Epigenomics. 2015;7(8):1327-38. |
