| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
Proteasome (chymotrypsin-like activity). AM-114 inhibits the chymotrypsin-like activity of the proteasome, preventing the degradation of ubiquitinated proteins. This leads to the accumulation of pro-apoptotic proteins and induction of apoptosis in cancer cells. The compound is a chalcone derivative with proteasome inhibitory activity.
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| ln Vitro |
At a dose of 1 µM, treatment with proteasome inhibitor IX (AM114; 0.1-10 µM; 14 days; HCT116 p53+/+ cells) led to a reduction in cell viability in p53+/+ and p53-/- cells of about 70% and 20%, respectively [1]. In colony formation experiments, proteasome inhibitor IX (AM114) demonstrated strong activity against p53+/+ cells, with an IC50 value of 0.6 µM [1]. The proteasome inhibitor IX (1 µM) was incubated with HCT116 p53+/+ cells (AM114). After 48 hours, 28% of the cells had positive Annexin V staining, and after 72 hours, 76% of the cells were dead[1]. Proteasome inhibitor IX (AM114) treatment prevents the 20S proteasome from acting in a chymotrypsin-like manner in vitro, which causes ubiquitinated p53 and other cellular proteins to accumulate significantly inside the cell [1].
AM-114 demonstrates potent proteasome inhibitory activity in vitro, with IC50 values in the low micromolar range against the chymotrypsin-like activity of the proteasome. The compound induces apoptosis in various cancer cell lines, including multiple myeloma, breast cancer, and lung cancer cells. It has been shown to inhibit cell proliferation and induce cell cycle arrest. |
| ln Vivo |
In vivo, AM-114 has been evaluated in xenograft models of cancer, showing significant tumor growth inhibition. The compound has demonstrated efficacy in multiple myeloma and other cancer models. Its anticancer activity is mediated through proteasome inhibition and induction of apoptosis. Preclinical studies have also assessed its safety profile and pharmacokinetics.
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| Enzyme Assay |
In vitro proteasome inhibition assays for AM-114 involve measuring the chymotrypsin-like activity of purified proteasome or cell lysates. The compound is incubated with a fluorogenic substrate (e.g., Suc-LLVY-AMC), and fluorescence is measured over time. IC50 values are determined from dose-response curves. Cytotoxicity assays are performed using cancer cell lines to assess antiproliferative activity.
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| Cell Assay |
Cellular assays for AM-114 involve culturing cancer cell lines, including multiple myeloma, breast cancer, and lung cancer cells. Cells are treated with AM-114 at varying concentrations (typically 0.1-10 µM). Cell viability is measured using MTT or other assays. Apoptosis is assessed by annexin V staining or caspase activity assays. Proteasome activity is measured using cell lysates and fluorogenic substrates.
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| Animal Protocol |
In vivo animal studies for AM-114 have been conducted in xenograft models of cancer. The compound is typically administered orally or intraperitoneally. Tumor growth is monitored, and tumor tissues are analyzed for proteasome activity, apoptosis markers, and ubiquitinated protein accumulation. Pharmacokinetic studies have also been performed to assess absorption and distribution. Dosing regimens vary.
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| ADME/Pharmacokinetics |
AM-114 is a small molecule with favorable pharmacokinetic properties in preclinical studies. It is orally bioavailable and has been shown to achieve therapeutic concentrations in tumor tissues. The compound is metabolized in the liver and excreted via the biliary and renal routes. Detailed pharmacokinetic parameters such as half-life and bioavailability have been characterized in animal models.
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| Toxicity/Toxicokinetics |
AM-114 has shown a favorable safety profile in preclinical studies, with no significant toxicity observed at therapeutic doses. The compound is generally well-tolerated in animal models. However, comprehensive toxicological data are limited. The compound is intended for research use only and is not approved for human therapeutic applications.
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| References |
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| Additional Infomation |
AM-114 is a chalcone derivative that inhibits the chymotrypsin-like activity of the proteasome, inducing apoptosis in cancer cells. It has shown potent anticancer activity against multiple myeloma, breast cancer, and lung cancer in preclinical studies. The compound is not approved for clinical use and is available for research purposes only. Further clinical development is needed to evaluate its therapeutic potential.
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| Molecular Formula |
C20H21B2NO5
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|---|---|
| Molecular Weight |
377.006445646286
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| Exact Mass |
377.16
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| CAS # |
856849-35-9
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| PubChem CID |
11639443
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
695.4±65.0 °C at 760 mmHg
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| Flash Point |
374.3±34.3 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.644
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| LogP |
4.14
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
556
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| Defined Atom Stereocenter Count |
0
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| SMILES |
B(O)(O)C1=CC=C(C=C1)/C=C\2/C(=O)/C(=C/C3=CC=C(C=C3)B(O)O)/CN(C2)C
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| InChi Key |
SRPIKXGUPAKTIZ-OTYYAQKOSA-N
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| InChi Code |
InChI=1S/C20H21B2NO5/c1-23-12-16(10-14-2-6-18(7-3-14)21(25)26)20(24)17(13-23)11-15-4-8-19(9-5-15)22(27)28/h2-11,25-28H,12-13H2,1H3/b16-10+,17-11+
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| Chemical Name |
[4-[(E)-[(5E)-5-[(4-boronophenyl)methylidene]-1-methyl-4-oxopiperidin-3-ylidene]methyl]phenyl]boronic acid
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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 : ~6.25 mg/mL (~16.58 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.62 mg/mL (1.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 6.2 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: ≥ 0.62 mg/mL (1.64 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 6.2 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6524 mL | 13.2622 mL | 26.5245 mL | |
| 5 mM | 0.5305 mL | 2.6524 mL | 5.3049 mL | |
| 10 mM | 0.2652 mL | 1.3262 mL | 2.6524 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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