SGC707

Catalog No.S7832 Batch:S783203

Technical Data

Formula

C₁₆H₁₈N₄O₂

Molecular Weight

298.34

CAS No.

1687736-54-4

Solubility (25°C)*

In vitro

DMSO

59 mg/mL (197.76 mM)

Ethanol

59 mg/mL (197.76 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

	5% DMSO 1 95% Corn oil	1.5mg/ml
	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	6.0mg/ml

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

SGC707 is a potent, selective and cell-active allosteric inhibitor of protein arginine methyltransferase 3 (PRMT3) with IC50 and K_d of 31 nM and 53 nM, respectively.

Targets

PRMT3 ^[1]	PRMT3 ^[1]
31 nM	53 nM(Kd)

In vitro

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. ^[1]

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. ^[1]

Protocol (from reference)

Kinase Assay:^{^[1]}	PRMT3 biochemical 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:^{^[1]}	Cell lines 293, LnCap, U2O s, HFF, MCF-7, and MDA-MB-231 cells Concentrations 100 μM Incubation Time 72 h Method 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.

Kinase Assay:^{^[1]}

PRMT3 biochemical 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:^{^[1]}

Cell lines
293, LnCap, U2O s, HFF, MCF-7, and MDA-MB-231 cells
Concentrations
100 μM
Incubation Time
72 h
Method
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.

References

[1] Kaniskan HÜ, et al. Angew Chem Int Ed Engl. 2015, 54(17), 5166-5170.

Selleck's SGC707 has been cited by 6 publications

PRMT3 drives glioblastoma progression by enhancing HIF1A and glycolytic metabolism [ Cell Death Dis, 2022, 13(11):943]	PubMed: 36351894
Revisiting Aldehyde Oxidase Mediated Metabolism in Drug-like Molecules: An Improved Computational Model [ J Med Chem, 2020, 31]	PubMed: 32191458
Everolimus enhances TRAIL-mediated anti-tumor activity of liver resident natural killer cells in mice [ Transpl Int, 2020, 33(2):229-243]	PubMed: 31560810
Immunogenicity of prostate cancer is augmented by BET bromodomain inhibition. [ J Immunother Cancer, 2019, 7(1):277]	PubMed: 31653272
Strategies for improving antitumor response in prostate cancer: BET Bromodomain inhibition and A2A Adenosine Receptor inhibition as methods of targeting prostate [ JScholarship, 2019, None]	PubMed: None
Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer [ Cancer Res, 2018, 78(20):5731-5740]	PubMed: 30135193

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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