SGC2085 is a potent and selective coactivator associated arginine methyltransferase 1 (CARM1) inhibitor with an IC₅₀ of 50 nM.

IC50: 50 nM (CARM1)^[1]

SGC2085 which features a methyl at position R1 and a 3,5-dimethylphenoxy at R2 has an IC₅₀ of 50 nM for CARM1 and is over 100-fold selective for CARM1 over PRMT6. These results indicate that the presence of a substituent at R1 is essential for potent and selective inhibition of CARM1. With the exception of PRMT6 (IC₅₀=5.2 μM), SGC2085 does not inhibit other PRMTs. Considering its small size (MW=312.4 Da), SGC2085 has an excellent selectivity profile, which can probably be further improved by exploiting differences in the binding sites of the two enzymes outside the arginine binding pocket. Compound SGC2085 also shows complete selectivity against a panel of 21 human protein methyltrans- ferases tested at three different concentrations (1,10, and 50 μM). To characterize the mechanism of action of SGC2085 in solution, IC₅₀ values are determined at various concentrations of SAM and peptide substrate. Increasing concentration of substrate peptide or cofactor does not affect IC₅₀ values, indicative of a noncompetitive mechanism of inhibition, which has been previously shown for other protein methyltransferase inhibitors binding at the substrate pocket^[1]. No cellular activity is observed for SGC2085 when tested up to 10 μM (48 h exposure in HEK293 cells), while methylation of BAF155 is abrogated by 10 μM of the dual CARM1/PRMT6 inhibitor MS049. We assume that the absence of cellular activity for SGC2085 is due to poor permeability^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

312.41

C₁₉H₂₄N₂O₂

1821908-48-8

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : ≥ 32 mg/mL (102.43 mM)

* “≥” means soluble, but saturation unknown.

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (8.00 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (8.00 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (8.00 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (8.00 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (8.00 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (8.00 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Ferreira de Freitas R, et al. Discovery of a Potent and Selective Coactivator Associated Arginine Methyltransferase 1 (CARM1) Inhibitor by Virtual Screening. J Med Chem. 2016 Jul 28;59(14):6838-47.

SGC2085 is dissolved in DMSO and diluted with appropriate medium before use. HEK293 cells are grown in 12-well plates in DMEM supplemented with 10% FBS, penicillin (100 U/mL), and streptomycin (100 μg/mL). Thirty percent confluent cells are treated with inhibitors or DMSO. After 48 h, media are removed and cells are lysed in 100 μL of total lysis buffer (20 mM Tris-HCl pH 8.0, 150 mM NaCl, 1 mM EDTA, 10 mM MgCl₂, 0.5% Triton X-100, 12.5 U/mL benzonase), complete EDTA-free protease inhibitor cocktail. After 3 min incubation at room temperature, SDS is added to 1% final concentration. Lysates are run on SDS-PAGE, and immunoblotting is done as outlined below to determine the levels of unmethylated and methylated BAF155^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Ferreira de Freitas R, et al. Discovery of a Potent and Selective Coactivator Associated Arginine Methyltransferase 1 (CARM1) Inhibitor by Virtual Screening. J Med Chem. 2016 Jul 28;59(14):6838-47.