| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| 500mg | |||
| Other Sizes |
| Targets |
Amsilarotene targets the retinoic acid receptor alpha (RAR-α), a nuclear receptor that regulates gene expression. It has a Ki of 2.4 nM for RAR-α and 400 nM for RAR-β. By antagonizing RAR-α, it inhibits retinoblastoma gene product (RB) phosphorylation and increases the presence of cyclin-dependent kinase (CDK) inhibitors, resulting in cell cycle arrest.
|
|---|---|
| ln Vitro |
In human epithelial ovarian cancer-derived cell lines, amsilarotene (0, 10, 25 μM; 24 hours) causes apoptosis in a concentration-dependent manner [2]. The proliferation of BxPC-3 and MIAPaCa-2 cells is inhibited by amsilarotene (10, 20 μM; 0, 3, 6, and 9 days) [3]. The fraction of G1-phase sensitive BxPC-3 cells increases in response to amsilarotene (10 μM; 48 hours) [3]. Over a period of 24 to 72 hours, amsilarotene (10 μM; 0, 3, 6, 24, 48, and 72 hours) suppresses the phosphorylation of the retinoblastoma gene product (RB) in BxPC-3 cells [3].
In vitro, amsilarotene demonstrates selective affinity for RAR-α with a Ki of 2.4 nM and a Ki of 400 nM for RAR-β. It induces apoptosis in human gastric cancer, hepatocellular carcinoma, and ovarian carcinoma cells. It inhibits RB phosphorylation and increases CDK inhibitors, resulting in cell cycle arrest. |
| ln Vivo |
Amsilarotene (8 mg/kg/day, orally, for 30 days) suppresses RMG-II tumor growth in nude mice [2].
In vivo, amsilarotene is an orally active synthetic retinoid that can be used for cancer research. It induces apoptosis in various cancer cell types. However, specific details of in vivo efficacy studies are not extensively detailed in the available literature. It is a research compound and is not approved for clinical use. |
| Enzyme Assay |
The in vitro receptor binding assay for amsilarotene typically involves radioligand displacement studies using RAR-α and RAR-β proteins. The compound's affinity (Ki) is determined by measuring its ability to displace a specific radiolabeled ligand from these receptors. Its functional antagonism is assessed using transactivation assays in cells expressing RAR-α.
|
| Cell Assay |
Apoptosis analysis[2]
Cell Types: RMG-I, RMG-II, RTSG, RMUG-S, RMUG-L and KF Cell Tested Concentrations: 0, 10, 25 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induced at certain concentrations Apoptosis was dependent on all cell lines except KF cells. Cell proliferation assay [3] Cell Types: BxPC-3, MIAPaCa-2, AsPC-1 Cell Tested Concentrations: 10 and 20 μM Incubation Duration: 0, 3, 6 and 9 days. Experimental Results: Inhibited the proliferation of BxPC-3 and MIAPaCa-2 cells, but not inhibited the proliferation of AsPC-1 cells. Cell cycle analysis [3] Cell Types: Sensitive BxPC-3 cells Tested Concentrations: 10 μM Incubation Duration: 48 hrs (hours) Experimental Results: The proportion of cells in G1 phase increased from 43% to 86% of untreated control cells In vitro cellular assays for amsilarotene assess its effects on cell cycle and apoptosis. Cancer cells are treated with amsilarotene, and cell cycle analysis is performed using flow cytometry. Apoptosis is assessed using Annexin V staining or caspase activity assays. Its effects on RB phosphorylation and CDK inhibitor levels are measured by Western blot. |
| Animal Protocol |
Animal/Disease Models: 6weeks old female BALB/c nu/nu subcutaneousRMG-II tumor mice [2]
Doses: 8 mg/kg/day Route of Administration: Oral administration for 30 days Experimental Results: Maximum tumor growth inhibition effect was seen after administration On day 31, relative tumor volume (RTV) diminished by 45%. In vivo animal studies for amsilarotene have been conducted in models of gastric cancer, hepatocellular carcinoma, and ovarian cancer to evaluate its antitumor efficacy. However, specific details of these studies are not extensively detailed in the available literature. It is a research compound and is not approved for clinical use. |
| ADME/Pharmacokinetics |
Amsilarotene is orally active. Its pharmacokinetic properties support oral administration. As a small molecule, it is absorbed from the gastrointestinal tract and distributed throughout the body. However, specific parameters such as half-life and bioavailability are not extensively detailed in the available literature.
|
| Toxicity/Toxicokinetics |
Specific toxicity data for amsilarotene are not extensively detailed in the available literature. As a RAR-α antagonist, its toxicity profile is likely related to its mechanism of action. However, its antitumor activity suggests a manageable safety profile. It is intended for research purposes only.
|
| References |
|
| Additional Infomation |
Amsilarotene is a retinoid compound with potential antitumor activity. Amsilarotene inhibits phosphorylation of the retinoblastoma gene product (RB) and increases the expression of two cyclin-dependent kinase (CDK) inhibitors, leading to cell cycle arrest. The drug also causes a cytotoxic decrease in the expression of cyclin A and thymidine synthase.
Amsilarotene (CAS 125973-56-0) is a synthetic retinobenzoic acid derivative and an orally active RAR-α antagonist with a Ki of 2.4 nM for RAR-α. It induces apoptosis in cancer cells and inhibits RB phosphorylation. It has a molecular formula of C20H27NO3Si2 and a molecular weight of 385.60. It is a research compound and is not approved for clinical use. |
| Molecular Formula |
C20H27NO3SI2
|
|---|---|
| Molecular Weight |
385.60428
|
| Exact Mass |
385.152
|
| CAS # |
125973-56-0
|
| PubChem CID |
9800306
|
| Appearance |
White to off-white solid powder
|
| Density |
1.1±0.1 g/cm3
|
| Boiling Point |
403.3±45.0 °C at 760 mmHg
|
| Flash Point |
197.7±28.7 °C
|
| Vapour Pressure |
0.0±1.0 mmHg at 25°C
|
| Index of Refraction |
1.550
|
| LogP |
7.73
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
26
|
| Complexity |
494
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
VVTNSTLJOVCBDL-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H27NO3Si2/c1-25(2,3)17-11-15(12-18(13-17)26(4,5)6)19(22)21-16-9-7-14(8-10-16)20(23)24/h7-13H,1-6H3,(H,21,22)(H,23,24)
|
| Chemical Name |
4-[[3,5-bis(trimethylsilyl)benzoyl]amino]benzoic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~259.34 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.48 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 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. Solubility in Formulation 2: 2.5 mg/mL (6.48 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 ultrasonication. 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 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5934 mL | 12.9668 mL | 25.9336 mL | |
| 5 mM | 0.5187 mL | 2.5934 mL | 5.1867 mL | |
| 10 mM | 0.2593 mL | 1.2967 mL | 2.5934 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
