| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
cIAP1
PROTAC AR Degrader-4 targets the androgen receptor (AR). It contains an AR binding group and an IAP ligand that recruits cellular inhibitor of apoptosis protein 1 (cIAP1). This molecule is a degrader that induces AR ubiquitination and degradation via the ubiquitin-proteasome pathway by bringing the AR into proximity with cIAP1. |
|---|---|
| ln Vitro |
IAPs-dependent Protein Erasers that are Specific and Nongenetic (SNIPERs) are two-component compounds that are created by combining an IAPs recognition structure with a target protein recognition structure. Three processes are involved in directing protein breakdown. 1. SNIPER's two recognition structures enable the formation of a complex that binds the target protein to IAPs, which contain E3 ligase activity. IAPs cause the target protein to become polyubiquitinated. 3. Proteases breakdown the polyubiquitinated protein.
PROTAC AR Degrader-4 is an AR degrader that incorporates an IAP ligand binding group, a linker, and an AR binding group. It is an AR degrader. The compound is a SNIPER that induces degradation of the androgen receptor. In vitro, it is expected to reduce AR protein levels in AR-positive prostate cancer cell lines. |
| ln Vivo |
In vivo, PROTAC AR Degrader-4 is designed to degrade the androgen receptor (AR). This activity has the potential to inhibit tumor growth in AR-dependent prostate cancer models. As a cIAP1-based degrader (SNIPER), it can effectively reduce AR protein levels in vivo, similar to other AR degraders.
|
| Enzyme Assay |
PROTAC AR Degrader-4 is a complete molecule. A cell-free binding assay is not typical for a full PROTAC. Researchers could use SPR or TR-FRET to confirm the binding of its individual components to their targets. A biochemical assay could measure the binding of the compound to the AR and to cIAP1, but its degradation activity requires a cellular context.
|
| Cell Assay |
Prostate cancer cells (e.g., LNCaP or VCaP) are seeded in 6-well plates and treated with PROTAC AR Degrader-4 TFA at various concentrations for 24-48 hours. After treatment, cells are lysed, and protein lysates are analyzed by Western blotting using an anti-AR antibody. The DC50 (concentration for 50% degradation) can be calculated from the densitometry data.
|
| Animal Protocol |
A standard in vivo animal protocol for PROTAC AR Degrader-4 would involve a mouse xenograft model of prostate cancer. Male athymic nude mice are implanted subcutaneously with LNCaP or VCaP cells. When tumors reach 100-150 mm3, mice are randomized and treated intraperitoneally with the degrader. Tumor volume is measured bi-weekly. AR degradation in tumors is confirmed by IHC.
|
| ADME/Pharmacokinetics |
PROTAC AR Degrader-4 TFA has a molecular weight of 884.03 and a molecular formula of C45H68F3N3O11. It is a solid that should be stored at -20degC for up to 3 years. In solution, it is stable for 1 year at -80degC. The TFA salt enhances solubility. Specific PK data are not available.
|
| Toxicity/Toxicokinetics |
Detailed toxicity data for PROTAC AR Degrader-4 TFA have not been reported. As a research chemical, standard laboratory safety precautions should be followed. Its safety profile has not been established for clinical use. The compound is handled as a potent biological research tool in laboratory settings.
|
| References | |
| Additional Infomation |
PROTAC AR Degrader-4 TFA is a research-grade PROTAC and is not approved for clinical use. It contains an IAP ligand binding group, a linker, and an AR binding group, operating through a cIAP1-based mechanism known as SNIPERs. This compound is a valuable research tool for studying AR function and for validating AR degradation as a therapeutic strategy for prostate cancer.
|
| Molecular Formula |
C45H68F3N3O11
|
|---|---|
| Molecular Weight |
884.03
|
| Related CAS # |
PROTAC AR Degrader-4;1351169-31-7
|
| Appearance |
White to off-white solid powder
|
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 :~200 mg/mL (~226.24 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (5.66 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 50.0 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: 5 mg/mL (5.66 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 50.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1312 mL | 5.6559 mL | 11.3118 mL | |
| 5 mM | 0.2262 mL | 1.1312 mL | 2.2624 mL | |
| 10 mM | 0.1131 mL | 0.5656 mL | 1.1312 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
