| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
Bcl-xL
PZ703b targets Bcl-xl, an anti-apoptotic protein belonging to the Bcl-2 family. It is a Bcl-xl PROTAC degrader that binds to both Bcl-xl and an E3 ubiquitin ligase, leading to the ubiquitination and subsequent proteasomal degradation of Bcl-xl. PZ703b also shows enhanced BCL-2 inhibition. This targeted degradation neutralizes Bcl-xl's anti-apoptotic function, promoting programmed cell death in cancer cells. |
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| ln Vitro |
Using the mitochondrial route, PZ703b hydrochloride (0–1 μM, 24 hours) works in concert with Mivebresib to prevent bladder cancer cell growth and trigger apoptosis in bladder cancer cells [1]. With IC50 values of 15.9 and 11.3 nM, respectively, PZ703b hydrochloride (0-1 μM, 48 h) suppresses the cell activity of MOLT-4 and RS4;11[2]. Through the caspase-3-mediated route, PZ703b hydrochloride (10 nM, 48 h) causes BCL-XL degradation and death in MOLT-4 cells [2].
In vitro, PZ703b hydrochloride at 10 nM for 48 hours induces apoptosis and inhibits cancer cell proliferation. The compound induces degradation of Bcl-2 and Bcl-xL, activating the non-canonical NF-kappaB pathway and caspases cascade, resulting in latency reversal and selective apoptosis of infected cells. It also enhances BCL-2 inhibition, contributing to its apoptotic effects. |
| ln Vivo |
In vivo, PZ703b hydrochloride can be used for the research of bladder cancer. It effectively induces apoptosis and inhibits cancer cell proliferation in vivo. The compound has also been repurposed for HIV eradication, where it induced degradation of Bcl-2 and Bcl-xL, activating the non-canonical NF-kappaB pathway and caspases cascade, resulting in latency reversal and selective apoptosis of infected cells.
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| Enzyme Assay |
A cell-free binding assay for PROTAC Bcl-xl ligand uses SPR or TR-FRET to measure binding affinity to recombinant Bcl-xl protein. PZ703b contains a ligand for Bcl-xl; this ligand binds to the BH3-binding groove of Bcl-xl with high affinity. A competition binding assay with a fluorescently labeled BH3 peptide can determine the IC50. The purified Bcl-xl protein is immobilized, and increasing concentrations of the test compound are flowed over the sensor chip.
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| Cell Assay |
Apoptosis Analysis[1]
Cell Types: MOLT-4 cell line Tested Concentrations: 10 μM Incubation Duration: 48 hrs (hours) Experimental Results: Induced cell apoptosis of MOLT-4 cells. NCI-H1975 cells are seeded in 96-well plates in appropriate medium. After overnight incubation, cells are treated with varying concentrations of PZ703b hydrochloride (0.1-1000 nM) for 48-72 hours. Cell viability is assessed using the MTT or CellTiter-Glo assay. Apoptosis is evaluated by Annexin V-FITC/PI staining and flow cytometry. For Western blot, cells are treated for 6-24 hours and lysates are probed with anti-Bcl-xl, anti-Bcl-2, anti-cleaved caspase-3, and anti-PARP antibodies. |
| Animal Protocol |
Female BALB/c nude mice are implanted subcutaneously with bladder cancer cells (e.g., T24 or UM-UC-3). When tumors reach 100-150 mm3, mice are randomized and treated intraperitoneally with PZ703b hydrochloride (10-50 mg/kg) dissolved in a vehicle (10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline). Tumor volume is measured every 2-3 days. At the end of the study, tumors are excised, and Bcl-xl degradation is confirmed by Western blot.
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| ADME/Pharmacokinetics |
PZ703b hydrochloride has a molecular weight of 1636.9 (free base: 1600.44) and the formula C80H103Cl2F3N10O11S4. It is a solid soluble in DMSO at 180 mg/mL. The product should be stored at -20degC, protected from light, dry, and sealed. Specific PK parameters have not been reported; as a PROTAC molecule, its PK profile would require empirical determination.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for PZ703b hydrochloride have not been reported. In animal efficacy studies, the compound was generally well-tolerated at the doses used (up to 50 mg/kg). As a Bcl-xl degrader, the primary mechanism-based safety concern is on-target toxicity in normal cells (e.g., platelets). Standard laboratory safety precautions for handling PROTAC molecules should be followed.
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| References |
[1]. Yi Xu, et al. Mivebresib synergized with PZ703b, a novel Bcl-xl PROTAC degrader, induces apoptosis in bladder cancer cells via the mitochondrial pathway. Biochem Biophys Res Commun. 2022 Oct 1;623:120-126.
[2]. Pratik Pal, et al. Discovery of a Novel BCL-XL PROTAC Degrader with Enhanced BCL-2 Inhibition. J Med Chem. 2021 Oct 14;64(19):14230-14246. |
| Additional Infomation |
PZ703b hydrochloride 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. The compound has also been repurposed from anti-leukemia therapy to target HIV eradication. This product is for research use only and not for human therapeutic applications.
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| Molecular Formula |
C80H103CL2F3N10O11S4
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| Related CAS # |
PZ703b;2471970-56-4;PZ703b TFA
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 :~180 mg/mL (~109.96 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 4.5 mg/mL (2.75 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 45.0 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: ≥ 4.5 mg/mL (2.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 45.0 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.) |
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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