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| Targets |
NI-57 targets the bromodomains of BRPF1, BRPF2 (BRD1), and BRPF3. BRPF proteins are epigenetic readers that recognize acetylated lysine residues on histones and are involved in chromatin remodeling and transcriptional regulation. By inhibiting the BRPF bromodomains, NI-57 disrupts the reading of acetylation marks, affecting gene expression programs. The compound shows highest potency against BRPF1.
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| ln Vitro |
NI-57 is an inhibitor of the plant homeodomain finger domain (BRPF) and the bromodomain with IC50 values of 3.1, 46, and 140 nM for BRPF1, BRPF2 (BRD1), and BRPF3, respectively. NI-57 exhibits a Kd of 31 ± 2 nM for the BRD of BRPF1, 110 ± 13 nM for BRD1, and 410 ± 47 nM for BRPF3. In contrast, the binding to BRD9 is rather poor, with a Kd of 1000 ± 130 nM. Measurements with titration calorimeter. TRIM24 (IC50, 1600 nM), BRD9 (IC50, 520 nM), and BRD4 (BD1) (IC50, 3700 nM) were all targets of little activity for NI-57. With GI50 values of 10.4 μM (NCI-H1703 cells), 14.7 μM (DMS114), 15.6 μM (HRA-19), and 16.6 μM (RERF-LC-Sq1), NI-57 similarly suppresses BRPF BRD in the nucleus but has no effect on the proliferation of numerous cancer cell lines. Furthermore, CCL-22 gene expression was decreased by 27.7 ± 9.4% upon NI-57 (10 μM)-induced BRPF1 inhibition [1].
In vitro, NI-57 potently inhibits BRPF1, BRPF2 (BRD1), and BRPF3 with IC₅₀ values of 3.1 nM, 46 nM, and 140 nM, respectively. Binding affinity for BRPF1 BRD is 31 ± 2 nM Kd, and for BRD1 is 110 ± 13 nM Kd. The compound demonstrates potent inhibition of BRPF bromodomains. In cellular assays, NI-57 engages BRPF proteins and modulates downstream gene expression. The compound is suitable for biochemical and cellular assays. Detailed bioactivity data are available in the primary literature. |
| ln Vivo |
In mice, NI-57 exhibits a high oral bioavailability [1].
In vivo data for NI-57 are limited in publicly available sources. Based on its potency and selectivity, the compound is expected to be useful for in vivo studies of BRPF function. The compound's physicochemical properties (MW 383.4, soluble in DMSO) suggest potential for in vivo administration. Further studies are needed to fully characterize its in vivo efficacy and pharmacokinetic profile. The compound is a research tool for epigenetic studies. |
| Enzyme Assay |
In vitro bromodomain binding assays for NI-57 typically use AlphaScreen, TR-FRET, or fluorescence polarization (FP) technology. Recombinant BRPF bromodomains (BRPF1, BRPF2/BRD1, BRPF3) are incubated with biotinylated acetylated histone peptide and the compound at various concentrations. The signal is measured according to the assay platform. IC₅₀ values are calculated from dose-response curves using nonlinear regression. Binding affinity (Kd) is determined by isothermal titration calorimetry (ITC) or surface plasmon resonance (SPR). Controls include DMSO vehicle and known BRPF inhibitors. Assays are performed in triplicate at room temperature.
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| Cell Assay |
For cell-based assays, relevant cell lines are cultured in DMEM with 10% FBS. Cells are seeded in 96-well or 6-well plates and treated with NI-57 at various concentrations for 4-24 hours. Target engagement is assessed by cellular BRPF occupancy using NanoBRET or CETSA. Gene expression changes are measured by RT-PCR or RNA-seq. Cell viability is assessed by MTT or CellTiter-Glo. Western blotting may be used to assess downstream signaling. All treatments include vehicle controls and are performed in triplicate.
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| Animal Protocol |
In vivo, NI-57 may be administered to rodents via IP or oral routes. Formulation may involve suspension in suitable vehicles (e.g., 0.5% methylcellulose or PEG-based formulations). Dosing regimens and concentrations would be determined based on preliminary pharmacokinetic studies. Pharmacodynamic studies assess target engagement by measuring BRPF occupancy in tissues. Plasma and tissue concentrations are measured by LC-MS/MS. All procedures follow institutional animal care guidelines.
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| ADME/Pharmacokinetics |
NI-57 (MW 383.4, C₁₉H₁₇N₃O₄S) is soluble in DMSO. Detailed pharmacokinetic parameters (bioavailability, half-life, clearance) are not extensively reported in publicly available sources. The compound is designed as a chemical probe for epigenetic research. Its physicochemical properties suggest potential for in vivo applications. Further ADME studies are needed to fully characterize its pharmacokinetic profile. The compound should be stored at -20°C.
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| Toxicity/Toxicokinetics |
Toxicology data for NI-57 are limited in publicly available sources. As a bromodomain inhibitor, potential off-target effects on other epigenetic readers should be considered. The compound is for research use only and not intended for human therapeutic applications. Standard safety pharmacology and toxicology studies would be required for therapeutic development. The compound should be handled with standard laboratory safety precautions.
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| References | |
| Additional Infomation |
NI-57 is a research-grade chemical probe for studying BRPF bromodomain function. Its primary applications include epigenetic research and chemical biology. The compound is not approved for clinical use and has not entered clinical trials. It is a valuable tool for elucidating the role of BRPF proteins in gene regulation. The compound is commercially available from various chemical suppliers for research purposes only.
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| Molecular Formula |
C19H17N3O4S
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| Molecular Weight |
383.420983076096
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| Exact Mass |
383.094
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| CAS # |
1883548-89-7
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| Related CAS # |
1883548-89-7;
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| PubChem CID |
91827373
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| Appearance |
White to off-white solid powder
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| LogP |
2.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
764
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(S(NC2C=CC3=C(C=2)C=C(C)C(=O)N3C)(=O)=O)=CC=C(C#N)C=C1OC
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| InChi Key |
UEMQPCYDWCSVCU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H17N3O4S/c1-12-8-14-10-15(5-6-16(14)22(2)19(12)23)21-27(24,25)18-7-4-13(11-20)9-17(18)26-3/h4-10,21H,1-3H3
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| Chemical Name |
4-cyano-N-(1,3-dimethyl-2-oxo-1,2-dihydroquinolin-6-yl)-2-methoxybenzenesulfonamide
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| Synonyms |
NI-57 NI 57 NI57.
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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 : ~100 mg/mL (~260.81 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.52 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 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 (6.52 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 | 2.6081 mL | 13.0405 mL | 26.0811 mL | |
| 5 mM | 0.5216 mL | 2.6081 mL | 5.2162 mL | |
| 10 mM | 0.2608 mL | 1.3041 mL | 2.6081 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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