| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
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| Targets |
VHL
The compound specifically targets the androgen receptor variant V7 (AR-V7). Its mechanism of action is by recruiting the VHL E3 ubiquitin ligase to the DNA-binding domain (DBD) of AR-V7. This leads to ubiquitination and subsequent proteasomal degradation of the AR-V7 protein, which lacks the ligand-binding domain targeted by conventional drugs. |
|---|---|
| ln Vitro |
In vitro, PROTAC AR-V7 degrader-1 demonstrates potent and selective degradation of the AR-V7 protein, with a DC50 (half-maximal degradation concentration) of 0.32 uM. By eliminating this constitutively active splice variant, the compound effectively shuts down a key pathway that drives tumor growth in the absence of androgens.
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| ln Vivo |
The compound is orally bioavailable, a crucial property for in vivo research. It has been developed for use in mouse models of prostate cancer. By effectively degrading AR-V7 in vivo, it can suppress the growth of tumors that are resistant to standard-of-care AR antagonists like enzalutabine, thereby validating AR-V7 as a therapeutic target.
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| Enzyme Assay |
Cellular degradation assays are performed in AR-V7-expressing prostate cancer cell lines (e.g., 22Rv1). Cells are treated with a concentration range of the PROTAC for 4-24 hours. Cells are harvested, lysed, and protein levels are measured by Western blot. The DC50 is calculated by densitometric analysis of the AR-V7 band. Selectivity for AR-V7 over other proteins is also assessed.
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| Cell Assay |
A reporter assay is used to measure AR-V7 transcriptional activity. Cells are co-transfected with an AR-V7 expression plasmid and an androgen response element (ARE)-luciferase reporter. The PROTAC is added, and after 24-48 hours, the cells are lysed and luminescence is measured. A decrease in signal confirms that target degradation leads to functional inactivation of the transcription factor.
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| Animal Protocol |
In vivo efficacy is evaluated in mice bearing 22Rv1 (AR-V7+) prostate cancer xenografts. PROTAC AR-V7 degrader-1 is administered via oral gavage daily. Tumor growth is measured with calipers. At study termination, tumors are harvested, and AR-V7 protein levels are measured by Western blot to confirm the correlation between in vivo target degradation and tumor growth inhibition.
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| ADME/Pharmacokinetics |
PROTAC AR-V7 degrader-1 is an orally bioavailable PROTAC, allowing for convenient once-daily oral administration in animal models. Its pharmacokinetic properties are optimized to achieve the necessary systemic exposure and tissue distribution to degrade AR-V7 in tumor xenografts, making it a robust in vivo tool.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies are focused on the selectivity of degradation. On-target toxicity would be related to the loss of AR-V7 function, which is largely specific to cancer cells. Off-target degradation (degrading other proteins containing a similar DBD) is a key parameter being evaluated to ensure the compound‘s safety as a research tool.
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| References | |
| Additional Infomation |
PROTAC AR-V7 degrader-1 is a first-of-its-kind chemical probe. Its development addresses a critical unmet need in prostate cancer research: the ability to pharmacologically target the constitutively active AR-V7 splice variant. This compound is a research-grade PROTAC intended for laboratory use only and has not been approved for clinical use.
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| Molecular Formula |
C41H52N6O6S2
|
|---|---|
| Molecular Weight |
789.02
|
| Exact Mass |
788.338
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| CAS # |
2767440-24-2
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| PubChem CID |
163196443
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| Appearance |
White to off-white solid powder
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| Density |
1.262±0.06 g/cm3(Predicted)
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| LogP |
5.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
55
|
| Complexity |
1250
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCOC4=CC=C(C=C4)C5=CSC(=N5)N6CCOCC6)O
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| InChi Key |
GGBZAQUSRYNTSQ-ASCDMGAVSA-N
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| InChi Code |
InChI=1S/C41H52N6O6S2/c1-26(28-9-11-30(12-10-28)36-27(2)42-25-55-36)43-38(50)34-22-31(48)23-47(34)39(51)37(41(3,4)5)45-35(49)8-6-7-19-53-32-15-13-29(14-16-32)33-24-54-40(44-33)46-17-20-52-21-18-46/h9-16,24-26,31,34,37,48H,6-8,17-23H2,1-5H3,(H,43,50)(H,45,49)/t26-,31+,34-,37+/m0/s1
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| Chemical Name |
(2S,4R)-1-[(2S)-3,3-dimethyl-2-[5-[4-(2-morpholin-4-yl-1,3-thiazol-4-yl)phenoxy]pentanoylamino]butanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide
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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) |
DMSO: 110 mg/mL (139.41 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 | 1.2674 mL | 6.3370 mL | 12.6739 mL | |
| 5 mM | 0.2535 mL | 1.2674 mL | 2.5348 mL | |
| 10 mM | 0.1267 mL | 0.6337 mL | 1.2674 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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