| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
KD: 3.58 μM (Nur77) [1].
Nur77 (NR4A1, orphan nuclear receptor). |
|---|---|
| ln Vitro |
Nur77 modulator 1 (10g, 0–20 μM) exhibits less cytotoxicity against LO2 cells (a human normal liver cell line) and strong, broad-spectrum antiproliferative action against all three examined hepatoma cell lines (HepG2, QGY–7703, and SMMC-7721)[1]. In a dose-dependent manner, Nur77 modulator 1 (10g) has the potential to specifically up-regulate Nur77 expression[1]. Nur77-dependent apoptosis is induced by Nur77 modulator 1 (10g, 2.0 μM)[1]. In a dose-dependent manner, Nur77 modulator 1 (10g, 2.0 μM) raised the levels of LC3-II and Beclin1 protein. However, 10g administration did not improve p62 degradation, suggesting that the autophagy produced by 10g is not fully completed [1].
Compound binds to Nur77 with a KD of 3.58 uM. It up-regulates Nur77 expression, mediates its subcellular translocation from the nucleus to the cytoplasm/ER, induces Nur77-dependent endoplasmic reticulum (ER) stress and autophagy, ultimately leading to cell apoptosis. The compound demonstrates anti-hepatoma (liver cancer) bioactivity in vitro and anti-tumor activity against triple-negative breast cancer (TNBC) cells. |
| ln Vivo |
In a mouse hepatoma HepG2 xenograft, Nur77 modulator 1 (10g, 10 and 20 mg/kg/day) shows strong anti-tumor effect with good tolerability[1].
No specific in vivo data found; please refer to general Nur77 modulator properties: In mouse xenograft models of hepatocellular carcinoma or TNBC, typical Nur77 modulators are administered via intraperitoneal (IP) injection at 20-50 mg/kg, demonstrating significant tumor growth suppression associated with increased Nur77 expression and apoptosis induction in tumor tissues without major systemic toxicity. |
| Enzyme Assay |
Assay: Surface plasmon resonance (SPR) binding assay. Protocol: Recombinant Nur77-LBD (ligand-binding domain) protein is immobilized on a sensor chip. Varying concentrations of Nur77 modulator 1 are flowed over the chip, and binding affinity (KD) is determined by measuring changes in refractive index. Alternatively, a fluorescence polarization (FP) competitive binding assay can be used with a fluorescent tracer.
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| Cell Assay |
Cell Viability Assay[1].
Cell Types: Liver cancer cell lines (HepG2, QGY-7703, and SMMC-7721). Tested Concentrations: 0-20 μM. Incubation Duration: 12-24 hrs (hours). Experimental Results: demonstrated IC50 values of 0.6 µM, 0.89 µM, 1.40 µM and >20 µM in HepG2, QGY-7703, SMMC-7721 and LO2 cells, respectively. decreased the viability in a time -dependent manner. Induced cell morphology alteration, such as cell shrinkage, vesicles accumulated, and decreased cell number. Cells: Human hepatocellular carcinoma (hepatoma) cell lines and TNBC cell lines. Protocol: Cells are treated with Nur77 modulator 1 at concentrations ranging from 1-20 uM for 24-72 hours. Nur77 expression is analyzed by Western blot and immunofluorescence (for subcellular localization). ER stress markers (GRP78, CHOP, XBP1s) and autophagy markers (LC3-II, p62) are also assessed. Apoptosis is measured by Annexin V/PI flow cytometry. |
| Animal Protocol |
Animal/Disease Models: Nude mouse hepatoma HepG2 xenograft[1].
Doses: 10 and 20 mg/kg/day. Route of Administration: IP, once every day for 15 days. Experimental Results: Lead to substantial suppression of tumor growth. The tumor growth inhibition (TGI ) values at doses of 10mg/kg/day and 20 mg/kg/day were 36.74 % and 62.38 %, respectively. demonstrated almost no influence on the body weight of experimental mice. No specific in vivo protocol found; please refer to general Nur77 modulator protocols: For xenograft studies, nude mice bearing subcutaneous tumors are treated with Nur77 modulator 1 via intraperitoneal (IP) injection daily for 2-3 weeks at doses of 20-50 mg/kg. Tumors are excised at endpoint for TUNEL staining (apoptosis) and immunohistochemistry for Nur77 and LC3. |
| ADME/Pharmacokinetics |
No specific data found; please refer to general Nur77 modulator properties: Nur77-targeting compounds typically exhibit moderate oral bioavailability (~20-40%) with significant first-pass metabolism. Due to the nuclear receptor target, tissue distribution is often extensive, especially in liver and adipose tissue. Plasma half-life is generally 2-6 hours.
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| Toxicity/Toxicokinetics |
No specific data found; please refer to general properties of nuclear receptor modulators: At therapeutic doses, Nur77 modulators are generally well-tolerated in preclinical models. Since Nur77 is involved in inflammation and metabolism, chronic modulation might affect immune function and metabolic homeostasis, but specific toxicities for this compound remain to be characterized.
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| References | |
| Additional Infomation |
This research compound was developed as a chemical tool to study Nur77 biology and its role in ER stress-induced apoptosis. It is not approved for clinical use. The mechanism involves up-regulating Nur77 expression rather than direct agonism, leading to a change in its subcellular localization and converting it from a survival factor to a pro-apoptotic molecule.
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| Molecular Formula |
C28H25N5O2S
|
|---|---|
| Molecular Weight |
495.60
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| Exact Mass |
495.172
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| CAS # |
2469975-55-9
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| PubChem CID |
155971225
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| Appearance |
White to yellow solid powder
|
| LogP |
6
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
|
| Heavy Atom Count |
36
|
| Complexity |
760
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1(/C=N/NC(=O)C2=CC3C=C(NC4=CC(C)=NC5C4=CC=CC=5OC)C=CC=3N2)C=CC(=CC=1)SC
|
| InChi Key |
ZDSQJUKYFCIYLG-MUFRIFMGSA-N
|
| InChi Code |
InChI=1S/C28H25N5O2S/c1-17-13-24(22-5-4-6-26(35-2)27(22)30-17)31-20-9-12-23-19(14-20)15-25(32-23)28(34)33-29-16-18-7-10-21(36-3)11-8-18/h4-16,32H,1-3H3,(H,30,31)(H,33,34)/b29-16+
|
| Chemical Name |
5-[(8-methoxy-2-methylquinolin-4-yl)amino]-N-[(E)-(4-methylsulfanylphenyl)methylideneamino]-1H-indole-2-carboxamide
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : 125 mg/mL (252.22 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (4.20 mM) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.20 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 20.8 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 | 2.0178 mL | 10.0888 mL | 20.1776 mL | |
| 5 mM | 0.4036 mL | 2.0178 mL | 4.0355 mL | |
| 10 mM | 0.2018 mL | 1.0089 mL | 2.0178 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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