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| Targets |
PRMT7 (protein arginine methyltransferase 7). SGC3027 is a prodrug that is converted intracellularly to its active form SGC8158. SGC8158 is a potent and selective SAM-competitive inhibitor of PRMT7, with an IC50 of less than 2.5 nM for inhibition of histone H2B (23-37) methylation. PRMT7 catalyzes the formation of monomethylated arginine (MMA) on target proteins, particularly symmetric dimethylation of arginine residues. PRMT7 is involved in gene regulation, DNA damage response, and cancer progression.
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| ln Vitro |
The prodrug of SGC8158, SGC3027, releases the active component after being lowered in cells by reductase. SGC3027 reduced HSP70 methylation in cell studies using C2C12 cells, with an IC50 value of 1.3 μM[2].
In cell-free biochemical assays, the active metabolite SGC8158 potently inhibits PRMT7 methyltransferase activity with an IC50 < 2.5 nM. The inhibition is SAM-competitive, meaning SGC8158 competes with the methyl donor S-adenosylmethionine (SAM) for binding to PRMT7. SGC8158 is highly selective for PRMT7 over other PRMTs (PRMT1, 3, 4, 5, 6, 8, 9) and other histone methyltransferases. The prodrug SGC3027 itself has minimal direct activity in cell-free assays, as it requires reductive activation to release SGC8158. |
| ln Vivo |
SGC3027 inhibits PRMT7 activity in cells following intracellular reduction to SGC8158. In cellular assays using C2C12 mouse myoblast cells, SGC3027 inhibits methylation of its substrate HSP70 with an IC50 of 1.3-2.4 uM. The compound reduces global symmetric dimethylarginine (SDMA) levels in cells without affecting asymmetric dimethylarginine (ADMA) levels, confirming PRMT7 selectivity. In B16.F10 melanoma cells, PRMT7 deficiency or inhibition with SGC3027 results in reduced DNMT expression, loss of DNA methylation in regulatory regions of endogenous retroviral elements (ERVs), causing their increased expression. SGC3027 treatment also modulates alternative splicing and affects PRMT4, 5, and 7-regulated splicing events.
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| Enzyme Assay |
PRMT7 enzymatic activity is measured using a methyltransferase assay format. Recombinant PRMT7 enzyme is incubated with a biotinylated peptide substrate (e.g., histone H2B 23-37 or RPS2 peptide), S-adenosyl-[3H]-methionine ([3H]-SAM), and test compound (SGC8158) at varying concentrations (0.001-10 uM) in assay buffer. After incubation, the reaction mixture is transferred to streptavidin-coated plates or scintillation proximity assay (SPA) beads, and incorporated radioactivity is counted. IC50 values are calculated from dose-response curves. For SAM-competition experiments, the concentration of SAM is varied, and inhibition patterns are analyzed using Lineweaver-Burk plots. Selectivity is assessed by testing against a panel of other PRMTs and methyltransferases.
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| Cell Assay |
Cellular PRMT7 inhibition is measured using C2C12, HEK293, or B16.F10 cells. Cells are treated with SGC3027 at concentrations ranging from 0.1-50 uM for 24-72 hours. For HSP70 methylation, C2C12 cells are treated with SGC3027 (0.1-50 uM) for 2 hours. Cells are lysed, and HSP70 is immunoprecipitated. Methylation of HSP70 is detected by Western blotting using a pan-methyl-arginine antibody (which detects monomethylarginine and asymmetric/symmetric dimethylarginine) or an SDMA-specific antibody. IC50 values for inhibition of substrate methylation are calculated from densitometry analysis. Global SDMA levels in whole-cell lysates are measured by Western blot with an SDMA-specific antibody. For DNA methylation analysis, genomic DNA is extracted after SGC3027 treatment and analyzed by bisulfite sequencing or methylation-sensitive restriction enzyme digestion. ERV expression is measured by qRT-PCR. Alternative splicing changes are analyzed by RT-PCR or RNA-seq.
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| Animal Protocol |
In vivo activity of SGC3027 has been demonstrated in mouse models. In B16.F10 melanoma tumor-bearing mice, SGC3027 treatment at doses typically ranging from 50-150 mg/kg (oral or intraperitoneal) suppresses PRMT7 activity in tumors. Pharmacodynamic endpoints include reduction in global SDMA levels in tumor tissue, increased ERV expression, and enhanced anti-tumor T cell immunity. SGC3027 treatment combined with immune checkpoint inhibitors (ICI) induces a strong anti-tumor T cell response and restrains tumor growth in vivo by increasing immune cell infiltration. The compound has been used to study PRMT7 role in cancer immunity and sensitivity to immunotherapy. Typical dosing regimens include daily or every-other-day administration for 1-2 weeks.
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| ADME/Pharmacokinetics |
As a prodrug, SGC3027 is designed to have improved cell permeability and oral bioavailability compared to the active parent compound SGC8158. Following administration, SGC3027 is absorbed and distributed to tissues, where it enters cells and is converted by intracellular reductases (likely thioredoxin reductase or similar) to SGC8158. Pharmacokinetic parameters for SGC3027 have not been extensively reported in publicly available literature. The compound is formulated as a solid or in DMSO for research use. In vivo formulations typically use DMSO:PEG300:water or similar vehicles. SGC3027 has sufficient stability and exposure in preclinical models to achieve pharmacodynamic effects. Detailed PK characterization would be required for further development.
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| Toxicity/Toxicokinetics |
Preclinical toxicology data for SGC3027 are limited to cell viability and tolerability studies. At concentrations up to 50 uM in cell culture, SGC3027 does not cause significant cytotoxicity in most cell lines. In mouse studies, SGC3027 at doses up to 150 mg/kg is generally well-tolerated, with no reports of significant body weight loss, organ toxicity, or mortality. However, formal toxicology studies have not been published. As with all experimental chemicals, standard laboratory safety precautions should be followed. The compound should be handled in a fume hood with appropriate PPE. Long-term toxicity studies would be required if SGC3027 were to be advanced toward clinical development.
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| References | |
| Additional Infomation |
SGC3027 is the first potent, selective, and cell-active chemical probe for PRMT7. It was developed by the Structural Genomics Consortium (SGC) as part of their chemical probe program. The compound is freely available to academic researchers to study PRMT7 biology. The prodrug approach was necessary because the highly polar active inhibitor SGC8158 does not penetrate cell membranes. SGC3027 is used in PRMT7 target validation studies, epigenetic research, and cancer immunology. The compound has been cited in publications studying PRMT7's role in alternative splicing, DNA methylation, and ERV expression. SGC3027 is not approved for human therapeutic use. For research applications, SGC3027 should be stored at -20degC as a powder and protected from light. It is also known by its chemical name and is sometimes referred to as SGC-3027.
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| Molecular Formula |
C41H47CLN6O6S
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|---|---|
| Molecular Weight |
787.37
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| Exact Mass |
786.296
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| CAS # |
2624313-13-7
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| PubChem CID |
137333447
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.7
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
55
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| Complexity |
1470
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| Defined Atom Stereocenter Count |
4
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| SMILES |
[C@H]1([C@H](O)[C@@H](CSCCCCN(CC2=CC(C3C=CC(Cl)=CC=3)=CC=C2)C(CC(C)(C)C2C(=O)C(C)=C(C)C(C=2C)=O)=O)O[C@H]1N1C=NC2C(N)=NC=NC=21)O
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| InChi Key |
MLJVGAYSVYMPSB-MSUKGTQXSA-N
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| InChi Code |
InChI=1S/C41H47ClN6O6S/c1-23-24(2)35(51)32(25(3)34(23)50)41(4,5)18-31(49)47(19-26-9-8-10-28(17-26)27-11-13-29(42)14-12-27)15-6-7-16-55-20-30-36(52)37(53)40(54-30)48-22-46-33-38(43)44-21-45-39(33)48/h8-14,17,21-22,30,36-37,40,52-53H,6-7,15-16,18-20H2,1-5H3,(H2,43,44,45)/t30-,36-,37-,40-/m1/s1
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| Chemical Name |
N-[4-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]butyl]-N-[[3-(4-chlorophenyl)phenyl]methyl]-3-methyl-3-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)butanamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~317.51 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (2.64 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2701 mL | 6.3503 mL | 12.7005 mL | |
| 5 mM | 0.2540 mL | 1.2701 mL | 2.5401 mL | |
| 10 mM | 0.1270 mL | 0.6350 mL | 1.2701 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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