| Size | Price | Stock | Qty |
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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%
NSC228155 is a novel and potent activator of EGFR, which binds to the sEGFR dimerization domain II and modulate EGFR tyrosine phosphorylation. Previous study found that NSC228155 could dose-dependently inhibit KIX–KID interaction as measured by the split RLuc assay. In living HEK 293T cells, NSC228155 could inhibit CREB-mediated gene transcription with an IC50 of 2.09 μM. NSC228155 also inhibited VP16-CREB-mediated gene transcription with an IC50 of 6.14 μM. Though this was around 3-fold higher than the IC50 of CREB-mediated gene transcription, such results indicated that NSC228155 was not particularly selective in inhibiting KIX–KID interaction inside these living cells.
| Targets |
Cu/Zn SOD1 (mediates EGFR activation) [1]
CREB-mediated gene transcription (IC50 = 3.7 μM) [2] |
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| ln Vitro |
Through the activity of SOD1, NSC 228155 (100 μM) increases EGFR tyrosine phosphorylation[1]. With IC50 values of 2.09 and 6.14 μM, respectively, NSC 228155 (compound 1) suppresses CREB- and VP16-CREB-mediated gene transcription in vivo HEK 293T cells [2]. In live HEK 293T cells, NSC 228155 is not selective for CREB-mediated gene transcription [2].
NSC228155 activated EGFR phosphorylation (Tyr1068) in A431 and HeLa cells, with maximal activation at 50 μM (2.8-fold and 2.3-fold increase respectively) [1] It induced stable dimerization of Cu/Zn SOD1 in A431 cells, as detected by non-reducing SDS-PAGE, with significant dimer formation at 25–100 μM [1] The compound promoted hydrogen peroxide (H2O2) generation in A431 cells, with a 3.5-fold increase at 50 μM compared to vehicle controls [1] Pretreatment with SOD1 siRNA or catalase (H2O2 scavenger) abolished NSC228155-induced EGFR activation, confirming dependence on Cu/Zn SOD1 and H2O2 [1] NSC228155 inhibited CREB-mediated gene transcription in HEK293T cells transfected with CRE-luciferase reporter, with an IC50 of 3.7 μM [2] It did not significantly inhibit NF-κB or AP-1 mediated transcription at concentrations up to 20 μM, showing selectivity for CREB [2] |
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| ln Vivo |
Up to now, there is no animal in vivo data reported.
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| Enzyme Assay |
Cu/Zn SOD1 dimerization assay: A431 cell lysates were prepared and incubated with NSC228155 (0–100 μM) in assay buffer for 1 hour at 37°C. Samples were resolved by non-reducing SDS-PAGE, transferred to membranes, and probed with anti-SOD1 antibody to detect dimer bands [1]
H2O2 generation assay: A431 cells were seeded in 96-well plates and loaded with H2O2-sensitive fluorescent probe. After 30 minutes, NSC228155 (0–100 μM) was added, and fluorescence intensity was measured at 30-minute intervals for 2 hours to quantify H2O2 production [1] CREB transcription assay: HEK293T cells were cotransfected with CRE-luciferase reporter and Renilla luciferase control plasmid. After 24 hours, NSC228155 (0.1–50 μM) was added, and cells were incubated for 16 hours. Luciferase activity was measured using a dual-luciferase assay system to calculate IC50 [2] |
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| Cell Assay |
EGFR phosphorylation assay: A431 and HeLa cells were seeded in 6-well plates and serum-starved for 12 hours. Cells were treated with NSC228155 (0–100 μM) for 1 hour, then lysed. Cell lysates were analyzed by Western blot using antibodies against phosphorylated EGFR (Tyr1068) and total EGFR [1]
SOD1 siRNA knockdown assay: A431 cells were transfected with SOD1 siRNA or scrambled siRNA for 48 hours. Cells were then treated with NSC228155 (50 μM) for 1 hour, and EGFR phosphorylation was detected by Western blot [1] Catalase pretreatment assay: A431 cells were pretreated with catalase (1000 U/mL) for 30 minutes, followed by NSC228155 (50 μM) treatment for 1 hour. EGFR phosphorylation was measured by Western blot [1] Transcription factor selectivity assay: HEK293T cells were transfected with NF-κB-luc or AP-1-luc reporters. After 24 hours, NSC228155 (0–20 μM) was added, and luciferase activity was measured to assess off-target effects [2] |
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| Animal Protocol |
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| References |
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| Additional Infomation |
NSC228155 activates EGFR through a unique mechanism involving Cu/Zn SOD1 dimerization and H2O2 generation, unlike ligand-dependent EGFR activation [1]. As a selective CREB-mediated gene transcription inhibitor, it has potential applications in diseases associated with abnormal CREB activity [2]. The compound exhibits dual biological activities depending on the cellular environment: activating EGFR in cells expressing Cu/Zn SOD1 and EGFR, and inhibiting CREB transcription [1][2].
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| Molecular Formula |
C11H6N4O4S
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| Molecular Weight |
290.25
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| Exact Mass |
290.01
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| CAS # |
113104-25-9
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| Related CAS # |
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| PubChem CID |
313619
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| Appearance |
Light yellow to orange solid powder
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| Density |
1.7±0.1 g/cm3
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| Boiling Point |
627.3±65.0 °C at 760 mmHg
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| Flash Point |
333.2±34.3 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.793
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| LogP |
0.07
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
369
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ICCFXXDUYSPKOL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H6N4O4S/c16-14-6-2-1-3-9(14)20-8-5-4-7(15(17)18)10-11(8)13-19-12-10/h1-6H
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| Chemical Name |
7-nitro-4-(1-oxidopyridin-1-ium-2-yl)sulfanyl-2,1,3-benzoxadiazole
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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 mg/mL (6.89 mM) in 15% Cremophor EL + 85% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.6 mg/mL (5.51 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 16.0 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 | 3.4453 mL | 17.2265 mL | 34.4531 mL | |
| 5 mM | 0.6891 mL | 3.4453 mL | 6.8906 mL | |
| 10 mM | 0.3445 mL | 1.7227 mL | 3.4453 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.
 Distribution of NBD compounds in breast cancer cells detected with fluorescent microscopy.Sci Rep.2016 Feb 17;6:21088. |
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 Detection of ROS in living cells exposed to NBD compounds by fluorescent microscopy.
Effects of SOD1 siRNA interference on tyrosine phosphorylation of EGFR, and expression of SOD1 in cancer cells exposed to NBD compounds. |
 Dimerization of SOD1 in cancer cells exposed to lipophilic NBD compounds, and SOD1 exposed to NBD compoundsin vitro.Sci Rep.2016 Feb 17;6:21088. |
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