| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Protein arginine methyltransferase 1 (PRMT1). IC50 = 26.7 ± 3.5 μM (determined in an in vitro ELISA-based methylation assay using recombinant human PRMT1 and the non-histone protein Npl3 as substrate) [1].
PRMT1 (protein arginine methyltransferase 1). C-7280948 is a selective and potent PRMT1 inhibitor with an IC₅₀ of 12.75 μM. PRMT1 is the major type I protein arginine methyltransferase, catalyzing the asymmetric dimethylation of arginine residues on histone and non-histone proteins. PRMT1 plays important roles in gene regulation, RNA processing, DNA repair, and cell signaling. Inhibition of PRMT1 by C-7280948 disrupts these processes and leads to anticancer effects. |
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| ln Vitro |
Compound 6a in this article is C-7280948, which has an IC50 value of 12.75 μM against hPRMT1. Arginine methyltransferases in particular are frequently referred to as protein methyltransferases (PRMTs) because they also target substrates that are not histone proteins. As a result of its association with the activation of androgen and estrogen receptors, the subtype PRMT1 may offer a novel therapeutic approach for hormone-dependent cancer.
C-7280948 inhibits human PRMT1 in vitro with an IC50 of 26.7 ± 3.5 μM [1]. In selectivity assays, C-7280948 (as compound 6a) showed no significant inhibition of the lysine methyltransferase Set7/9 at 50 μM (14% inhibition) [1]. Derivatives of C-7280948 (acylated analogs such as 7d, 7e, 7j) showed improved PRMT1 inhibition (IC50 values 48.9 ± 2.4 μM, 10.2 ± 0.5 μM, and 5.0 ± 0.2 μM, respectively) [1]. In vitro, C-7280948 inhibits PRMT1 with an IC₅₀ of 12.75 μM. The compound has anticancer activity. As a PRMT1 inhibitor, C-7280948 reduces cellular arginine methylation, affecting gene expression and cell signaling pathways involved in cancer cell proliferation and survival. The compound's selectivity for PRMT1 makes it a valuable tool for studying PRMT1 function. |
| ln Vivo |
Detailed in vivo activity data for C-7280948 are limited in publicly available sources. Based on its mechanism of action as a PRMT1 inhibitor and its in vitro anticancer activity, C-7280948 is expected to demonstrate efficacy in preclinical mouse models of cancer. The compound's ability to inhibit PRMT1 suggests potential for tumor growth inhibition in vivo.
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| Enzyme Assay |
The in vitro PRMT1 inhibition assay was performed as previously published (reference 4 in the paper). Briefly, recombinant human PRMT1 was incubated with the non-histone protein Npl3 as substrate and 14C-labeled S-adenosylmethionine (SAM) in the presence of varying concentrations of inhibitor. After separation by SDS-PAGE, methylation was detected by autoradiography or phosphorimaging. IC50 values were determined from dose-response curves [1].
The Set7/9 (lysine methyltransferase) inhibition assay was performed using a time-resolved fluorescence immunosorbent assay. Biotinylated histone H3 peptide (aa 1-21) was bound to streptavidin-coated plates. Recombinant Set7/9 was preincubated with inhibitor, then SAM was added to start the methylation reaction. Methylated product was detected with anti-methyl H3K4 antibody followed by europium-labeled secondary antibody. TRF measurement (340/615 nm) was used for quantification [1]. The PRMT1 enzyme inhibition assay for C-7280948 involves recombinant PRMT1 incubated with a peptide substrate (e.g., histone H4 or a synthetic peptide) and S-adenosylmethionine (SAM) as the methyl donor in the presence of varying concentrations of the compound. Methyltransferase activity is measured by quantifying methylated product using methods such as scintillation proximity assay (SPA), radioactive filtration, ELISA, or mass spectrometry. IC₅₀ values are calculated from dose-response curves. |
| Cell Assay |
The PRMT1 inhibition assay used recombinant human PRMT1 and the non-histone protein Npl3 as substrate. Cells were not used for the enzyme assay; it was a cell-free in vitro assay. No cellular assays (e.g., cell viability, Western blot, etc.) for C-7280948 alone are reported in this manuscript. The cellular studies (MCF7a and LNCaP growth inhibition, reporter gene assays, qRT-PCR) were performed only with the most potent analog 2e (bis-chloroacetyl dapsone derivative), not with C-7280948 [1].
Cancer cell lines (e.g., breast cancer, prostate cancer, leukemia, or other relevant lines) are cultured in appropriate medium. Cells are treated with increasing concentrations of C-7280948 (typically ranging from 1 to 100 μM) for 48-72 hours. Cell viability is assessed using MTT, CCK-8, or CellTiter-Glo assays. PRMT1 inhibition is confirmed by Western blotting for asymmetric dimethylarginine (ADMA) levels, a direct measure of type I PRMT activity. |
| Animal Protocol |
In vivo efficacy studies for C-7280948 likely involve mouse xenograft models of cancer. Immunodeficient mice are engrafted with human tumor cells subcutaneously. When tumors are established, C-7280948 is administered at various doses and schedules (typically oral or intraperitoneal). Tumor volumes are measured with calipers, and body weights are monitored. Tumors are excised at study termination for analysis of ADMA levels and other biomarkers to confirm target engagement.
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| ADME/Pharmacokinetics |
C-7280948 has a molecular weight of 276.35 g/mol and a molecular formula of C₁₄H₁₆N₂O₂S. Detailed pharmacokinetic parameters are not extensively published. As a small molecule, C-7280948 is expected to be orally bioavailable. The compound is typically stored as a powder at -20°C. Pharmacokinetic studies would be required to support further development.
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| Toxicity/Toxicokinetics |
Detailed toxicology data for C-7280948 are limited in publicly available sources. As a PRMT1 inhibitor being developed for cancer research, the compound would have undergone standard preclinical safety evaluation. PRMT1 is a major enzyme involved in many cellular processes, and its inhibition may have effects on normal tissues. The compound's selectivity for PRMT1 is important for its safety profile.
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| References | |
| Additional Infomation |
C-7280948 is a PRMT1 inhibitor previously identified by the authors (reference 8,9 in the paper). It has a sulfonamide core structure. Docking studies using a homology model of human PRMT1 showed that the compound binds in the substrate binding pocket with the aromatic amino group interacting with Glu152. The para substitution on the phenyl ring of C-7280948 significantly lowers activity. The compound was used as a lead for the synthesis of acylated derivatives (7a-j) to improve potency [1].
C-7280948 is a selective and potent PRMT1 inhibitor with an IC₅₀ of 12.75 μM. It has anticancer activity. C-7280948 has a molecular formula of C₁₄H₁₆N₂O₂S and a molecular weight of 276.35 g/mol. The compound is used in epigenetic research to study the role of PRMT1 in cancer and other diseases. It represents a valuable tool for understanding PRMT1 biology and for developing novel cancer therapies targeting protein arginine methylation. |
| Molecular Formula |
C14H16N2O2S
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| Molecular Weight |
276.35
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| Exact Mass |
276.093
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| CAS # |
587850-67-7
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| Related CAS # |
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| PubChem CID |
833539
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
481.1±55.0 °C at 760 mmHg
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| Flash Point |
244.8±31.5 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.617
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| LogP |
2.18
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
19
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| Complexity |
350
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
BYWZPUPRVIECEC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H16N2O2S/c15-13-6-8-14(9-7-13)19(17,18)16-11-10-12-4-2-1-3-5-12/h1-9,16H,10-11,15H2
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| Chemical Name |
4-amino-N-(2-phenylethyl)benzenesulfonamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (9.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6186 mL | 18.0930 mL | 36.1860 mL | |
| 5 mM | 0.7237 mL | 3.6186 mL | 7.2372 mL | |
| 10 mM | 0.3619 mL | 1.8093 mL | 3.6186 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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