| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Bcl-xL 0.6 nM (IC50) VHL
PROTAC Bcl-xL degrader-2 targets Bcl-xL. It is based on a von Hippel-Lindau (VHL) ligand that recruits the VHL E3 ubiquitin ligase. By bringing Bcl-xL into proximity with the VHL E3 ligase, this molecule induces the ubiquitination and subsequent proteasomal degradation of Bcl-xL. It has an IC50 of 0.6 nM. |
|---|---|
| ln Vitro |
In THP-1 cells, PROTAC Bcl-xL degrader-2 (PROTAC 6; 0.1 nM–10 μM; 24 hours) treatment reduces the amount of Bcl-xL protein[1]. In MOLT-4 cells, caspase 3/7 activity is inhibited by PROTAC Bcl-xL degrader-2 (PROTAC 6) at an IC50 of 466 nM[1].
In vitro, PROTAC Bcl-xL degrader-2 (PROTAC 6) treatment reduces the amount of Bcl-xL protein in THP-1 cells (a human leukemia monocytic cell line) in a concentration-dependent manner. It also inhibits caspase 3/7 activity in MOLT-4 cells with an IC50 of 466 nM, indicating its ability to induce apoptosis downstream of Bcl-xL degradation. |
| ln Vivo |
In vivo, PROTAC Bcl-xL degrader-2 is designed to degrade the Bcl-xL protein. By promoting the degradation of Bcl-xL, it can induce apoptosis in Bcl-xL-dependent tumors. This compound is a potent degrader based on a VHL ligand, and it is intended for use in cancer research to study the effects of Bcl-xL depletion in vivo.
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| Enzyme Assay |
PROTAC Bcl-xL degrader-2 is a complete PROTAC molecule. A cell-free binding assay is not typical for a full PROTAC as its mechanism requires the intracellular ubiquitin-proteasome system. The reported IC50 value (0.6 nM) is likely derived from a biochemical assay measuring Bcl-xL binding or from a cellular degradation assay.
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: THP-1 cells Tested Concentrations: 0.1 nM-10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Led to monotonic decreases in observed Bcl-xL protein. THP-1 cells are seeded in 6-well plates and treated with PROTAC Bcl-xL degrader-2 at concentrations ranging from 0.1 nM to 10 microM for 24 hours. After treatment, cells are harvested and lysed. Protein lysates are analyzed by Western blot using an anti-Bcl-xL antibody to measure the reduction in Bcl-xL protein levels. GAPDH is used as a loading control. |
| Animal Protocol |
A standard in vivo animal protocol for PROTAC Bcl-xL degrader-2 would involve a mouse xenograft model of leukemia or lymphoma. Female NSG or BALB/c nude mice are injected intravenously with MOLT-4 or THP-1 cells. When engraftment is confirmed, mice are treated intraperitoneally with the degrader. Tumor burden is measured by bioluminescence or flow cytometry.
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| ADME/Pharmacokinetics |
PROTAC Bcl-xL degrader-2 has a molecular weight of 1329.6 and the molecular formula C68H80N8O14S3. It is a solid powder that should be stored at -20degC for up to 3 years. In solution, it is stable for 6 months at -80degC. It is soluble in DMSO. Specific PK parameters have not been reported.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for PROTAC Bcl-xL degrader-2 are not available. As a research chemical, it should be handled with standard laboratory safety precautions, including the use of PPE and a chemical fume hood. On-target toxicity due to Bcl-xL degradation in normal tissues (e.g., platelets) is a potential concern.
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| References | |
| Additional Infomation |
PROTAC Bcl-xL degrader-2 is a research-grade PROTAC and is not approved for clinical use. It is a potent degrader of Bcl-xL (Bcl-2 family member) based on a VHL ligand, with an IC50 of 0.6 nM. This compound is a valuable research tool for studying the role of Bcl-xL in cancer and for validating it as a therapeutic target. It is for research use only.
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| Molecular Formula |
C68H80N8O14S3
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|---|---|
| Molecular Weight |
1329.60
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| Appearance |
White to off-white solid powder
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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 (~75.21 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 10 mg/mL (7.52 mM) in 10% DMSO + 90% Corn Oil (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 100.0 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 | 0.7521 mL | 3.7605 mL | 7.5211 mL | |
| 5 mM | 0.1504 mL | 0.7521 mL | 1.5042 mL | |
| 10 mM | 0.0752 mL | 0.3761 mL | 0.7521 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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