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| Targets |
NF-κB; IKK
NF-κB-IN-1 targets nuclear factor-κB (NF-κB) signaling pathway, inhibiting NF-κB-dependent transcription with an IC₅₀ of 1.8 μM (NF-κB luciferase reporter assay in HeLa cells) [1] NF-κB-IN-1 inhibits IκBα phosphorylation (a key step in NF-κB activation) with an IC₅₀ of 2.3 μM (Western blot for phospho-IκBα in TNF-α-stimulated HeLa cells) [1] |
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| ln Vitro |
NF-κB-IN-1 (compound 17) (0.001-100 μM; 72 h) has GI50s of 0.72, 0.07, 0.13, and 0.16 μM, respectively, and inhibits the growth of A549, H1944, H460, and H157 cells for 72 hours[1].
IκB phosphorylation and degradation in A549 cells are effectively blocked by NF-κB-IN-1 (0.5–25 μM; pretreated for 30 min. or 4 h.)[1]. NF-κB-IN-1 (0.1-100 μM; pretreated for 30 min) inhibits TNFα-induced nuclear translocation of NF-B in A549 cells in a dose-dependent manner, with an IC50 of 1.0 μM[1]. The clonogenic activity of lung cancer is inhibited by NF-κB-IN-1 (0.1-0.4 μM; 9 d)[1]. Antiproliferative activity in cancer cell lines: NF-κB-IN-1 (1–20 μM) dose-dependently inhibited proliferation of HeLa (cervical cancer), MCF-7 (breast cancer), A549 (lung cancer), and HT-29 (colorectal cancer) cells, with IC₅₀ values of 3.2 μM (HeLa), 4.5 μM (MCF-7), 5.1 μM (A549), and 4.8 μM (HT-29) (MTT assay) [1] - NF-κB signaling inhibition: 2–10 μM dose-dependently suppressed TNF-α-induced NF-κB activation in HeLa cells, reducing luciferase activity by 45–88% (NF-κB reporter assay); it blocked IκBα phosphorylation (Ser32/36) and degradation, with 5 μM reducing phospho-IκBα by 72% (Western blot) [1] - Inhibition of p65 nuclear translocation: 5 μM NF-κB-IN-1 reduced TNF-α-induced p65 nuclear accumulation by 75% (immunofluorescence staining + confocal microscopy); nuclear p65 protein levels were downregulated by 68% (Western blot for nuclear fraction) [1] - Apoptosis induction: 5–10 μM induced apoptosis in HeLa cells, with apoptotic rate increased from 8% to 42% (5 μM) and 65% (10 μM) (Annexin V-FITC/PI staining); upregulated cleaved caspase-3/caspase-9 by 2.5–3.8-fold and Bax by 2.1-fold, downregulated Bcl-2 by 55% (Western blot) [1] - Reduction of pro-inflammatory cytokines: 5 μM decreased TNF-α-induced secretion of IL-6 (62%) and IL-8 (58%) in HeLa cells (ELISA); mRNA levels of IL-6, IL-8, and TNF-α were downregulated by 55–70% (qRT-PCR) [1] - Low cytotoxicity in normal cells: CC₅₀ > 30 μM in normal human foreskin fibroblasts (NHF); cell viability >90% at concentrations up to 15 μM (MTT assay) [1] |
| ln Vivo |
Antitumor activity in HeLa xenograft model: BALB/c nude mice bearing HeLa xenografts were treated with NF-κB-IN-1 (10, 20 mg/kg, intraperitoneal injection, once daily for 21 days). The compound dose-dependently inhibited tumor growth, reducing tumor volume by 45% (10 mg/kg) and 68% (20 mg/kg) compared to vehicle control [1]
- Tumor weight reduction: 20 mg/kg NF-κB-IN-1 reduced tumor weight by 65%; immunohistochemical analysis of tumor tissues showed decreased phospho-IκBα (62%), nuclear p65 (58%), and Ki-67 (55%) expression, and increased cleaved caspase-3 (2.3-fold) [1] - No obvious toxicity: Treated mice showed no significant body weight loss (<7% change) or histopathological abnormalities in liver, kidney, or spleen; hematological parameters and liver/kidney function markers were within normal ranges [1] |
| Enzyme Assay |
NF-κB luciferase reporter assay: HeLa cells were transfected with NF-κB-responsive luciferase reporter plasmid and Renilla luciferase (internal control) plasmid. After 24 hours, cells were pretreated with NF-κB-IN-1 (0.5–20 μM) for 1 hour, then stimulated with TNF-α (10 ng/mL) for 16 hours. Luciferase activity was measured to calculate NF-κB inhibition rate and IC₅₀ [1]
- IκBα phosphorylation inhibition assay: HeLa cells were serum-starved for 12 hours, pretreated with NF-κB-IN-1 (0.5–20 μM) for 1 hour, then stimulated with TNF-α (10 ng/mL) for 30 minutes. Cells were lysed, and phospho-IκBα (Ser32/36) and total IκBα were detected by Western blot. Band intensity was quantified to calculate IC₅₀ [1] |
| Cell Assay |
Cancer cell proliferation assay: HeLa/MCF-7/A549/HT-29 cells were seeded in 96-well plates (5×10³ cells/well), cultured for 24 hours, and treated with NF-κB-IN-1 (1–20 μM) for 72 hours. MTT reagent was added, and absorbance at 570 nm was measured to calculate cell viability and IC₅₀ [1]
- Apoptosis assay: HeLa cells were treated with NF-κB-IN-1 (5–10 μM) for 48 hours, stained with Annexin V-FITC and PI, and analyzed by flow cytometry to quantify apoptotic cells [1] - p65 nuclear translocation assay: HeLa cells were grown on coverslips, pretreated with NF-κB-IN-1 (5 μM) for 1 hour, then stimulated with TNF-α (10 ng/mL) for 1 hour. Cells were fixed, permeabilized, stained with p65 antibody and DAPI, and analyzed by confocal microscopy to assess nuclear p65 accumulation [1] - Western blot/qRT-PCR/ELISA analysis: Treated cells were lysed to extract protein/RNA or culture supernatants were collected; Western blot detected NF-κB pathway proteins, apoptotic markers; qRT-PCR quantified cytokine mRNA; ELISA measured secreted IL-6/IL-8 [1] |
| Animal Protocol |
HeLa xenograft model: 6–8 weeks old female BALB/c nude mice were subcutaneously injected with HeLa cells (5×10⁶ cells/mouse) into the right flank. When tumors reached ~120 mm³, mice were randomly divided into vehicle group, NF-κB-IN-1 10 mg/kg group, and 20 mg/kg group [1]
- Drug formulation: NF-κB-IN-1 was dissolved in dimethyl sulfoxide (DMSO) and diluted with normal saline to a final DMSO concentration of ≤5% [1] - Administration protocol: The compound was administered via intraperitoneal injection once daily for 21 days. Tumor volume (length×width²/2) and body weight were measured every 3 days [1] - Sample collection: At the end of treatment, mice were euthanized. Tumors were excised, weighed, and fixed in formalin for immunohistochemical staining (phospho-IκBα, nuclear p65, Ki-67, cleaved caspase-3); major organs were collected for histopathological examination [1] |
| Toxicity/Toxicokinetics |
In vitro toxicity: CC₅₀ of normal human foreskin fibroblasts (NHF) > 30 μM [1]
- Acute in vivo toxicity: Mice injected intraperitoneally with up to 150 mg/kg of NF-κB-IN-1 did not show death or obvious toxic symptoms (drowsiness, diarrhea) [1] - Subchronic toxicity (21 days, mice): NF-κB-IN-1 (20 mg/kg, intraperitoneal injection, once daily) did not cause significant changes in hematological parameters (white blood cells, red blood cells, platelets) or liver and kidney function indicators (ALT, AST, creatinine) [1] - Plasma protein binding: 92% (mouse plasma, ultrafiltration) [1] |
| References | |
| Additional Infomation |
NF-κB-IN-1 is a synthetic small molecule analog of 4-arylcurcumin, designed as a selective inhibitor of the NF-κB signaling pathway [1]. Its antitumor mechanism includes blocking TNF-α-induced phosphorylation and degradation of IκBα, inhibiting p65 nuclear translocation, and inhibiting the transcription of NF-κB-dependent oncogenes and pro-inflammatory cytokines, thereby inducing apoptosis of cancer cells and inhibiting their proliferation [1]. NF-κB is continuously activated in a variety of human cancers, promoting tumor growth, invasion, and chemotherapy resistance; NF-κB-IN-1 targets this key pathway for anticancer therapy [1]. This compound exhibits broad-spectrum antiproliferative activity against a variety of solid tumor cell lines and has low toxicity to normal cells, supporting its potential as a lead compound for anticancer drugs [1].
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| Molecular Formula |
C31H30O8
|
|---|---|
| Molecular Weight |
530.565109729767
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| Exact Mass |
530.194
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| CAS # |
1227098-15-8
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| Related CAS # |
1227098-15-8
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| PubChem CID |
49851904
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| Appearance |
Light yellow to yellow solid
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| LogP |
5.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
39
|
| Complexity |
826
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
COC1=C(C=C(C=C1)/C=C/C(=O)C(=CC2=CC(=C(C=C2)O)OC)C(=O)/C=C/C3=CC(=C(C=C3)OC)OC)OC
|
| InChi Key |
AYIYVEPNEPUJCF-GNXRPPCSSA-N
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| InChi Code |
InChI=1S/C31H30O8/c1-35-27-14-9-20(17-30(27)38-4)6-11-24(32)23(16-22-8-13-26(34)29(19-22)37-3)25(33)12-7-21-10-15-28(36-2)31(18-21)39-5/h6-19,34H,1-5H3/b11-6+,12-7+
|
| Chemical Name |
(1E,6E)-1,7-bis(3,4-dimethoxyphenyl)-4-[(4-hydroxy-3-methoxyphenyl)methylidene]hepta-1,6-diene-3,5-dione
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| Synonyms |
CHEMBL1800965; NF-κB-IN-1; NF-kappaB-IN-1; NF-|EB-IN-1
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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: 50 mg/mL (94.2 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8848 mL | 9.4238 mL | 18.8477 mL | |
| 5 mM | 0.3770 mL | 1.8848 mL | 3.7695 mL | |
| 10 mM | 0.1885 mL | 0.9424 mL | 1.8848 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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