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| Targets |
PROTAC Bcl-xL ligand-1 targets Bcl-xL, a member of the Bcl-2 family of apoptosis regulator proteins. This ligand is specifically designed to bind to Bcl-xL. It can be used in the synthesis of PROTACs to recruit an E3 ubiquitin ligase (such as VHL) to Bcl-xL, leading to its ubiquitination and proteasomal degradation, thereby inducing apoptosis in cancer cells.
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| ln Vitro |
A linker separates the two ligands that make up PROTACs; one ligand is for an E3 ubiquitin ligase, and the other is for the target protein. Target proteins are selectively degraded by PROTACs by taking advantage of the intracellular ubiquitin-proteasome system[1].
PROTAC Bcl-xL ligand-1 is a ligand for Bcl-xL. Its primary activity is its ability to bind to Bcl-xL. When conjugated into a full PROTAC molecule, the resulting construct leads to the degradation of Bcl-xL, which is a key survival protein in many cancers. This ligand is a valuable tool for generating potent Bcl-xL degraders. |
| ln Vivo |
PROTAC Bcl-xL ligand-1 is used in vivo as a building block for PROTACs. A PROTAC degrader of Bcl-xL has shown potent anti-tumor activity in xenograft mouse models. While the ligand alone has no therapeutic activity, it is a critical component for developing effective protein degraders that can target Bcl-xL in vivo.
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| Enzyme Assay |
A cell-free binding assay for PROTAC Bcl-xL ligand-1 would use SPR or ITC. Recombinant Bcl-xL protein is immobilized on a sensor chip. Increasing concentrations of PROTAC Bcl-xL ligand-1 are flowed over the chip to measure the binding affinity (Kd). A TR-FRET-based competition assay could also be used. The compound is typically dissolved in DMSO.
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| Cell Assay |
PROTAC Bcl-xL ligand-1 is a small molecule used for PROTAC synthesis. It is not used directly in a typical cell-based assay without being conjugated into a full PROTAC. The resulting PROTAC is used to treat cells, and the levels of Bcl-xL protein are measured by Western blot. Cell viability and apoptosis markers (e.g., Caspase-3/7) are also assessed.
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| Animal Protocol |
A standard in vivo animal protocol for a Bcl-xL PROTAC would involve mouse xenograft models. Female BALB/c nude mice are implanted subcutaneously with cancer cells (e.g., H146). When tumors reach 100-150 mm3, mice are randomized and treated intraperitoneally with the PROTAC. Tumor volume and body weight are measured. Bcl-xL degradation in tumors is confirmed by Western blot or IHC.
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| ADME/Pharmacokinetics |
PROTAC Bcl-xL ligand-1 has a molecular weight of 724.63 and the molecular formula C32H29IN4O4S2. The product 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 data are not available.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for PROTAC Bcl-xL ligand-1 have not been reported. As a research chemical, standard laboratory safety precautions should be followed. The compound should be handled using appropriate PPE in a well-ventilated area. It is not intended for human use.
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| References | |
| Additional Infomation |
PROTAC Bcl-xL ligand-1 (CAS: 3029365-95-2) is not an approved drug; it is strictly a research tool for PROTAC development. It is a versatile ligand for Bcl-xL, enabling the synthesis of potent and selective degraders. Bcl-xL is a promising target for cancer therapy due to its role in blocking apoptosis. This product is for research use only.
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| Molecular Formula |
C32H29IN4O4S2
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|---|---|
| Molecular Weight |
724.63
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| Exact Mass |
724.068
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| CAS # |
3029365-95-2
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| PubChem CID |
162642762
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
43
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| Complexity |
943
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC(=O)C1=C(SC(=N1)N2CCC3=C(C2)C(=CC=C3)C(=O)NC4=NC5=CC=CC=C5S4)CCCOC6=CC=C(C=C6)I
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| InChi Key |
NOZZAZZDPDCLQI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C32H29IN4O4S2/c1-2-40-30(39)28-27(11-6-18-41-22-14-12-21(33)13-15-22)43-32(35-28)37-17-16-20-7-5-8-23(24(20)19-37)29(38)36-31-34-25-9-3-4-10-26(25)42-31/h3-5,7-10,12-15H,2,6,11,16-19H2,1H3,(H,34,36,38)
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| Chemical Name |
ethyl 2-[8-(1,3-benzothiazol-2-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]-5-[3-(4-iodophenoxy)propyl]-1,3-thiazole-4-carboxylate
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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 (~138.0 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (2.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (20.8 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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: 2.08 mg/mL (2.87 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Suspended solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (20.8 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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 | 1.3800 mL | 6.9001 mL | 13.8001 mL | |
| 5 mM | 0.2760 mL | 1.3800 mL | 2.7600 mL | |
| 10 mM | 0.1380 mL | 0.6900 mL | 1.3800 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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