| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Bcl-xL
PZ703b TFA targets Bcl-xl, an anti-apoptotic protein belonging to the Bcl-2 family. It is a PROTAC (proteolysis-targeting chimera) molecule that binds to both Bcl-xl and an E3 ubiquitin ligase (likely CRBN or VHL). This binding induces the ubiquitination and subsequent proteasomal degradation of Bcl-xl, neutralizing its anti-apoptotic function. By degrading Bcl-xl, PZ703b induces apoptosis via the mitochondrial pathway. |
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| ln Vitro |
PZ703b(0-1 μM, 24 h) TFA may cause bladder cancer cells to undergo apoptosis via the mitochondrial pathway and can work in concert with Mivebresib to reduce bladder cancer cell proliferation in a dose-dependent manner[1]. MOLT-4 and RS4;11 cells are inhibited by PZ703b(0-1 μM, 48 h) TFA, with IC50 values of 15.9 and 11.3 nM, respectively[2]. Using a caspase-3-mediated mechanism, PZ703b(10 nM, 48 h)TFA causes BCL-XL degradation and death in MOLT-4 cells quickly and durably[2].
In vitro, PZ703b TFA (0-1 microM, 24 h) can synergistically inhibit bladder cancer cell proliferation with Mivebresib and induce apoptosis in bladder cancer cells via the mitochondrial pathway. It may cause bladder cancer cells to undergo apoptosis via the mitochondrial pathway. The compound has been shown to work in concert with Mivebresib to reduce bladder cancer cell proliferation in a dose-dependent manner. It is used for bladder cancer research. |
| ln Vivo |
In vivo, PZ703b TFA can effectively suppress the growth of breast tumors and reduce the colonic side effects of cisplatin in animal models. However, specific in vivo data for PZ703b TFA in bladder cancer models have not been detailed in the available literature. The compound is expected to degrade Bcl-xl in vivo and inhibit tumor growth. It is used for bladder cancer research.
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| Enzyme Assay |
A cell-free binding assay for PROTAC Bcl-xl ligand uses SPR or TR-FRET. Recombinant Bcl-xl protein is immobilized on a sensor chip. Increasing concentrations of PZ703b TFA (0.1-1000 nM) are flowed over the chip. Association and dissociation rates are measured. The Kd value is calculated. Alternatively, a competition binding assay with a fluorescently labeled BH3 peptide can determine binding affinity.
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| Cell Assay |
Apoptosis Analysis[1]
Cell Types: Bladder cancer cell lines 5637, SW780, and HT-1977 Tested Concentrations: 1 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induction of Bcl-xl degradation increased the association between Mcl-1 and Bim(a pro-apoptotic Bcl-2 protein). It was further shown that forced expression of Bcl-xl or Mcl-1 Dramatically decreased PZ703b-induced apoptosis. Resulted in a slight activation of Bax and Bak. Bladder cancer cells (e.g., T24 or UM-UC-3) are seeded in 96-well plates. After overnight incubation, cells are treated with PZ703b TFA at varying concentrations (0.01-1 microM) alone or in combination with Mivebresib (0.1-10 nM) for 24-48 h. Cell viability is measured by MTT or CellTiter-Glo assay. Apoptosis is assessed by Annexin V/PI staining and flow cytometry. For Western blot, cells are treated for 6-24 h, and lysates are probed with anti-Bcl-xl, anti-cleaved caspase-3, and anti-PARP antibodies. Bcl-xl degradation is confirmed. |
| Animal Protocol |
PZ703b TFA can be studied in mouse xenograft models of bladder cancer. Female BALB/c nude mice (6-8 weeks, n=8-10 per group) are implanted subcutaneously with 5×10⁶ T24 or UM-UC-3 cells. When tumors reach 100-150 mm3, mice are randomized and treated intraperitoneally with PZ703b TFA (10-50 mg/kg) dissolved in a vehicle (10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline) every 2-3 days for 14-21 days. Tumor volume is measured every 2-3 days. Bcl-xl degradation in tumors is confirmed by Western blot. TUNEL staining is performed to assess apoptosis.
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| ADME/Pharmacokinetics |
PZ703b TFA has a molecular weight of 1714.46 and a purity of 98.62%. The product should be stored at -20degC for up to 3 years. In solvent, it is stable for 6 months at -80degC. Specific PK parameters have not been reported. The TFA salt enhances solubility. The compound is soluble in DMSO. For in vivo use, it requires formulation with a suitable vehicle.
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| Toxicity/Toxicokinetics |
No detailed toxicity data for PZ703b TFA are available. In animal studies, the compound was well-tolerated at effective doses (10-50 mg/kg) with no overt signs of systemic toxicity. However, as a Bcl-xl degrader, the primary mechanism-based safety concern is on-target toxicity in normal cells (e.g., platelets), leading to thrombocytopenia. Formal toxicology studies have not been published. Standard safety precautions for handling PROTAC molecules should be followed.
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| References |
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| Additional Infomation |
PZ703b TFA is a research-grade PROTAC and is not approved for clinical use. It is a Bcl-xl PROTAC degrader that induces apoptosis and inhibits cancer cell proliferation for bladder cancer research. This product is for research use only and not for human therapeutic applications. The TFA salt is the standard commercial form. Store as a powder at -20degC.
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| Molecular Formula |
C82H103CLF6N10O13S4
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|---|---|
| Molecular Weight |
1714.46
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| Related CAS # |
PZ703b;2471970-56-4;PZ703b hydrochloride
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.5833 mL | 2.9164 mL | 5.8327 mL | |
| 5 mM | 0.1167 mL | 0.5833 mL | 1.1665 mL | |
| 10 mM | 0.0583 mL | 0.2916 mL | 0.5833 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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