| 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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| 500mg |
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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].
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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]. |
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| ln 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]. |
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| 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].
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| Animal Protocol |
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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].
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| 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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