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| 5mg |
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| 10mg |
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| Targets |
BWA-522 intermediate-2 is a chemical building block and does not have a direct pharmacological target. The final PROTAC molecule, BWA-522, targets the androgen receptor (AR), specifically the N-terminal domain (AR-NTD). The androgen receptor is a nuclear receptor that plays a critical role in prostate cancer development and progression. AR-NTD is a challenging target for conventional small molecule inhibitors, making PROTAC-mediated degradation an attractive approach.
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| ln Vitro |
As a synthetic intermediate, BWA-522 intermediate-2 itself does not exhibit biological activity. The final PROTAC molecule BWA-522 shows potent degradation activity against AR-FL and AR-V7 in VCaP cells, with DC50 values of 0.73 μM and 0.67 μM, respectively. This degradation activity is mediated through the ubiquitin-proteasome pathway. BWA-522 also demonstrates oral bioavailability of 40.5% in mouse and 69.3% in dog.
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| ln Vivo |
The in vivo activity of BWA-522 has been demonstrated in a LNCaP xenograft model, where oral administration at 60 mg/kg resulted in 76% tumor growth inhibition. The PROTAC degrader is currently under investigation for the treatment of castration-resistant prostate cancer. BWA-522 intermediate-2 itself is not administered in vivo, as it is a synthetic building block rather than a therapeutic agent.
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| Enzyme Assay |
Non-cell-based assays for BWA-522 intermediate-2 are not applicable as it is a synthetic intermediate. However, the final PROTAC molecule BWA-522 can be characterized in biochemical assays measuring AR binding and degradation. Standard protocols for assessing PROTAC activity include: incubating purified AR protein with BWA-522 in the presence of cereblon and E2 ubiquitin-conjugating enzymes, and monitoring ubiquitination and degradation by Western blot.
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| Cell Assay |
Cell-based assays for BWA-522 intermediate-2 are not applicable as it is a synthetic intermediate. However, the final PROTAC molecule BWA-522 is evaluated in cellular assays using AR-dependent prostate cancer cell lines such as VCaP and LNCaP. A representative protocol includes: culturing cells in appropriate medium, treating with BWA-522 at various concentrations for 24–72 hours, and measuring AR-FL and AR-V7 levels by Western blot to determine DC50 values. Cell viability is assessed using MTT or CellTiter-Glo assays.
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| Animal Protocol |
In vivo animal studies with BWA-522 intermediate-2 are not applicable as it is a synthetic intermediate. However, the final PROTAC molecule BWA-522 has been evaluated in xenograft mouse models of prostate cancer, such as LNCaP xenografts. A typical protocol involves subcutaneous implantation of LNCaP cells in immunodeficient mice, allowing tumors to reach a certain size, administering BWA-522 via oral gavage at 60 mg/kg, monitoring tumor growth and body weight, and harvesting tumors for histopathological analysis.
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| ADME/Pharmacokinetics |
BWA-522 intermediate-2 is a synthetic intermediate and is not evaluated for pharmacokinetic properties as a drug. However, the final PROTAC molecule BWA-522 exhibits oral bioavailability of 40.5% in mouse and 69.3% in dog, supporting its development as an orally bioavailable therapeutic. BWA-522 intermediate-2 is stored as a powder at -20°C for up to 3 years and is soluble in DMSO.
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| Toxicity/Toxicokinetics |
As a synthetic intermediate for research use, BWA-522 intermediate-2 is not intended for human therapeutic use, and comprehensive toxicological data are not available. Standard laboratory safety precautions should be followed when handling the compound. The compound is typically stored at -20°C in a sealed container, protected from moisture and light. Appropriate personal protective equipment should be worn during handling.
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| References | |
| Additional Infomation |
BWA-522 intermediate-2 is a validated convergent building block for the synthesis of BWA-522, a first-in-class, orally bioavailable PROTAC degrader of the androgen receptor N-terminal domain. BWA-522 achieves DC50 values of 0.73 μM (AR-FL) and 0.67 μM (AR-V7) in VCaP cells and delivers 76% tumor growth inhibition in a LNCaP xenograft model following oral administration at 60 mg/kg. The intermediate is referenced in the primary literature (Journal of Medicinal Chemistry, 2023). This intermediate enables reproducible and high-yield access to the final PROTAC molecule for the treatment of castration-resistant prostate cancer.
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| Molecular Formula |
C29H40CLNO5
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| Molecular Weight |
518.08
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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) |
Typically soluble in DMSO (e.g. 10 mM)
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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 | 1.9302 mL | 9.6510 mL | 19.3020 mL | |
| 5 mM | 0.3860 mL | 1.9302 mL | 3.8604 mL | |
| 10 mM | 0.1930 mL | 0.9651 mL | 1.9302 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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