| 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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| Other Sizes |
Purity: =99.50%
| Targets |
Nrf2-Gpx4
AS-HK014 (Gingerenone A) targets multiple pathways: it is a dual inhibitor of JAK2 and S6K1 pathways, and an activator of the Nrf2-Gpx4 signaling axis. By inhibiting JAK2 and S6K1, it suppresses tumor growth and induces apoptosis in cancer cells. Activation of the Nrf2-Gpx4 pathway provides antioxidant and cytoprotective effects, reducing ferroptosis. This dual mechanism contributes to its anticancer and anti-inflammatory activities. |
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| ln Vitro |
Gin A diminished the cellular ATP content and decreased the cell viability of the MTS assay in several breast cancer cell lines. It also showed a delayed G2/M response to breast cancer cells (MCF7 and MDA-MB-231). N-acetylcysteine (NAC), an oxidative stress inhibitor, can revert these responses of antiproliferation and G2/M delay. The oxidative stress and senescence responses of Gin A were further validated by increasing reactive oxygen species, mitochondrial superoxide, and β-galactosidase activity, which were reverted by NAC. Gin A also upregulated senescence-associated gene expressions. In addition to oxidative stress, Gin A also induced DNA damage responses by increasing γH2AX level and foci and generating 8-hydroxyl-2'-deoxyguanosine in breast cancer cells, which were reverted by NAC. Therefore, Gin A promotes antiproliferation and senescence of breast cancer cells induced by oxidative stress.[1]
In vitro, Gingerenone A diminishes cellular ATP content and decreases cell viability in several breast cancer cell lines, including MCF7 and MDA-MB-231. It causes a G2/M phase delay in cancer cells following oxidative stress and senescence responses. It increases reactive oxygen species, mitochondrial superoxide, and β-galactosidase activity. Gingerenone A also induces DNA damage responses by increasing γH2AX level and foci. These effects are reversed by N-acetylcysteine (NAC), indicating involvement of oxidative stress. |
| ln Vivo |
In this study, we investigated the protective effect of GA on dextran sodium sulfate (DSS)-induced SLI in mice and its mechanism. The SLI was established by adding 4% DSS in the drinking water of mice, and the effects of GA (5, 20 mg/kg, p.o., once a day for 7 days) in hepatic tissues were analyzed. HepG2 cells were induced by lipopolysaccharide (LPS) to detect the effect of GA on ferroptosis and the underlying mechanism. Pathological damage was determined by H&E. Liver parameters (AST and ALT), antioxidant enzyme activities (MDA and SOD), and the level of Fe2+ in the liver were detected by kits. Cytokine levels (TNF-α, IL-1β, and IL-6) and Gpx4 activity in the liver were detected by ELISA. Finally, the activation of nuclear factor erythroid 2-like 2 (Nrf2) was detected to explore the mechanism. The results indicated that GA significantly attenuated DSS-induced hepatic pathological damage, liver parameters, and cytokine levels and increased the antioxidant enzyme activities. Moreover, GA attenuated ferroptosis in DSS-induced liver injury and upregulated Gpx4 expression in DSS-induced mice. Mechanistic experiments revealed that GA activated Nrf2 in mice. Taken together, this study demonstrates that GA can alleviate ferroptosis in SLI in DSS-induced colitis mice, and its protective effects are associated with activating the Nrf2-Gpx4 signaling pathway. [2]
In vivo, Gingerenone A protects against secondary liver injury (SLI) in mice with dextran sodium sulfate (DSS)-induced colitis. It attenuates DSS-induced hepatic pathological damage, liver parameters (AST and ALT), and cytokine levels (TNF-α, IL-1β, and IL-6), and increases antioxidant enzyme activities. It attenuates ferroptosis in DSS-induced liver injury and upregulates Gpx4 expression. These effects are associated with activation of the Nrf2-Gpx4 signaling pathway. |
| Enzyme Assay |
Livers Biochemical Analysis[2]
Briefly, about 40 mg of frozen liver was taken and homogenized by adding 300 μL of PBS, and then, the supernatant was extracted. Then, supernatants were used to determinate the levels of ALT and AST, following the manufacturer’s protocol. Detection of Cytokines and Oxidative Stress[2] The following assays were performed using the above extracted liver protein supernatant. The levels of hepatic TNF-α (EK282/4), IL-1β (EK201B), and IL-6 (EK206/3) in the liver were determined according to the instructions of the ELISA kit. The activities of hepatic GSH (A006-1-2) and MDA (A003-1-2) were determined by a kit. Detection of Fe2+ Release Assay and GPX4 Enzymatic Activity[2] The following assays were performed using the above extracted liver protein supernatant. The supernatants were used to determinate the hepatic Fe2+ release (TC1015) level following the manufacturer’s protocol and the GPX4 enzymatic activity (MM-44846M2) following the manufacturer’s protocol. The in vitro enzyme/receptor binding assays for AS-HK014 include measurement of its activation of the Nrf2-Gpx4 axis (EC50 = 24 μM). Its dual inhibition of JAK2 and S6K1 pathways is typically assessed using kinase activity assays with purified enzymes. These cell-free assays provide a direct measure of the compound's potency against its targets. The compound's ability to scavenge reactive oxygen species can also be assessed in cell-free systems. |
| Cell Assay |
Cell Viability[1]
Viability was assessed using an ATP kit, MTS cell proliferation assay, and trypan blue reagent based on the user manual’s instruction. Cell Cycle Detection[1] To stain DNA, 7-Aminoactinomycin D (7AAD) (1 μg/mL, 30 min, 37 °C) was used in order to determine cell cycle phases. The 7AAD-stained cells were resuspended in PBS to perform flow cytometer. Cell cycle phases were analyzed by FlowJo software version 10. In vitro cellular assays for AS-HK014 assess its antiproliferative and pro-apoptotic effects in cancer cell lines. Breast cancer cell lines (MCF7 and MDA-MB-231) are treated with various concentrations of the compound, and cell viability is measured using MTS assays. Cell cycle analysis is performed using flow cytometry. Oxidative stress markers such as reactive oxygen species, mitochondrial superoxide, and β-galactosidase activity are measured. DNA damage is assessed by γH2AX levels and foci. |
| Animal Protocol |
SPF Male C57 mice were purchased from the Experimental Animal Service Center of Guangzhou University of Chinese Medicine (SCXK 2020-0051). The mice were housed at a temperature of 20–24 °C, relative humidity of 55 ± 10%, and a light/dark cycle of 12–12 h. All animal care and experimental studies were approved by the Animal Ethics Committee of Guangzhou University of Chinese Medicine and followed its guidelines.[2]
As described in our previous publication, the SLI mouse model was treated by 7 days of dextran sodium sulfate (DSS; MW, 36 000–50 000) free drinking. As shown in Figure 1B, mice were randomly grouped into an average of 10 mice per group. The groups were set as the control group (Ctrl), 4% DSS group, 4% DSS+5-ASA (50 mg/kg) group, 4% DSS+GA (5 mg/kg) group (GAL), and 4% DSS+GA (20 mg/kg) group (GAH). During DSS treatment, mice in the control were given distilled water, and the rest of the groups were given the corresponding drugs; body weights were assessed daily. The livers were removed, and a portion was cut and soaked in 4% paraformaldehyde for pathology; the remainder was frozen at −80 °C.[2] In vivo animal studies for AS-HK014 have been conducted in mice with DSS-induced colitis and secondary liver injury. The SLI was established by adding 4% DSS in the drinking water, and Gingerenone A (5, 20 mg/kg, p.o., once a day for 7 days) was administered. Endpoints included pathological damage (H&E), liver parameters (AST and ALT), antioxidant enzyme activities (MDA and SOD), Fe²⁺ levels, cytokine levels (TNF-α, IL-1β, IL-6), and Gpx4 activity. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic data for AS-HK014 are not extensively detailed in the available literature. As a natural product, its oral bioavailability may be limited. However, its in vivo efficacy at 5 and 20 mg/kg p.o. suggests that it reaches sufficient systemic concentrations. The compound's pharmacokinetic properties would be important for its development as a therapeutic agent, but specific data are not provided.
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| Toxicity/Toxicokinetics |
Specific toxicity data for AS-HK014 are not extensively detailed in the available literature. However, Gingerenone A has been reported to selectively kill cancer cells while exhibiting minimal toxicity toward normal cells. This suggests a favorable safety profile. In the DSS-induced colitis model, the compound was well-tolerated at the doses tested. Comprehensive toxicological studies would be required for clinical development.
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| References |
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| Additional Infomation |
Gingerenone A is a diarylheptane compound. Gingerenone A has been reported in ginger (Zingiber officinale), and relevant data are available for reference.
AS-HK014 (Gingerenone A) is a natural diarylheptanoid polyphenol isolated from ginger with dual JAK2/S6K1 inhibitory and Nrf2-Gpx4 activating properties. It induces oxidative stress and senescence in cancer cells, leading to G2/M phase delay and apoptosis. It has demonstrated protective effects against ferroptosis in secondary liver injury. The compound is a research tool for studying cancer, oxidative stress, and inflammation. It is not approved for clinical use. |
| Molecular Formula |
C21H24O5
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|---|---|
| Molecular Weight |
356.41226
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| Exact Mass |
356.162
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| Elemental Analysis |
C, 70.77; H, 6.79; O, 22.44
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| CAS # |
128700-97-0
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| PubChem CID |
5281775
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| Appearance |
Typically exists as light yellow to yellow ointment at room temperature
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| Density |
1.183g/cm3
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| Boiling Point |
571.3ºC at 760mmHg
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| Flash Point |
200.3ºC
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| Vapour Pressure |
1.19E-13mmHg at 25°C
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| Index of Refraction |
1.583
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| LogP |
3.805
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
26
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| Complexity |
450
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(CCC1C=CC(O)=C(OC)C=1)/C=C/CCC1C=CC(O)=C(OC)C=1
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| InChi Key |
FWDXZNKYDTXGOT-GQCTYLIASA-N
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| InChi Code |
InChI=1S/C21H24O5/c1-25-20-13-15(8-11-18(20)23)5-3-4-6-17(22)10-7-16-9-12-19(24)21(14-16)26-2/h4,6,8-9,11-14,23-24H,3,5,7,10H2,1-2H3/b6-4+
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| Chemical Name |
(E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one
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| Synonyms |
ASHK014; AS-HK-014; Gingerenone A; ASHK-014; AS-HK014; AS HK014;
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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 (280.6 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8058 mL | 14.0288 mL | 28.0576 mL | |
| 5 mM | 0.5612 mL | 2.8058 mL | 5.6115 mL | |
| 10 mM | 0.2806 mL | 1.4029 mL | 2.8058 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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