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| Targets |
PROTAC AR/AR-V7 degrader-1 (27c) is a dual PROTAC degrader that specifically targets both full-length androgen receptor (AR) and its splice variant AR-V7 for proteasomal degradation. AR-V7 is a critical driver of resistance to standard AR-targeted therapies (e.g., enzalutamide, abiraterone) in castration-resistant prostate cancer (CRPC). By simultaneously degrading both forms, this PROTAC is designed to overcome resistance mechanisms that rely on AR-V7 signaling. The molecule recruits the cereblon (CRBN) E3 ubiquitin ligase to the AR, tagging it for degradation.
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| ln Vitro |
PROTAC AR/AR-V7 degrader-1 (27c) effectively inhibits the transcriptional activity of the AR signaling pathway. In 22RV1 cells, the IC50 of PROTAC AR/AR-V7 degrader-1 (27c) is 0.9 μM[1]. PROTAC AR/AR-V7 degrader-1 (27c) overcomes drug resistance in advanced prostate cancer expressing AR splice variants[1].
In vitro, PROTAC AR/AR-V7 degrader-1 (27c) is a potent dual degrader, with DC50 values of 2.67 uM for full-length AR and 2.64 uM for AR-V7. It effectively inhibits the transcriptional activity of the androgen receptor signaling pathway. In 22RV1 prostate cancer cells, which endogenously express AR-V7, the compound has an IC50 of 0.9 uM for inhibiting cell viability. The PROTAC overcomes drug resistance in advanced prostate cancer cells expressing AR splice variants. |
| ln Vivo |
Detailed in vivo data for PROTAC AR/AR-V7 degrader-1 was not available in the search results. However, the compound's ability to degrade AR and AR-V7 and its activity in 22RV1 cells, a cell line resistant to standard AR antagonists, strongly suggests it would have significant antitumor efficacy in preclinical models of CRPC. In vivo studies would likely involve xenograft models of CRPC (e.g., 22RV1 or patient-derived xenografts (PDXs)) to assess tumor growth inhibition and the degree of target degradation in the tumor tissue.
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| Enzyme Assay |
The degradation activity is assessed in cell-based assays, not cell-free systems. However, to confirm PROTAC-mediated ternary complex formation, a time-resolved fluorescence resonance energy transfer (TR-FRET) assay can be used. Purified AR protein, purified cereblon (CRBN) protein, and a linker-compatible fluorescent tag are mixed. Varying concentrations of PROTAC AR/AR-V7 degrader-1 (0.01-100 uM) are added. The formation of the AR-PROTAC-CRBN ternary complex is detected by TR-FRET, and the complex formation constant (Kd) is calculated.
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| Cell Assay |
For cell-based degradation assays, 22RV1 prostate cancer cells are seeded in 6-well plates (3×10⁵ cells/well) and treated with varying concentrations of PROTAC AR/AR-V7 degrader-1 (0.1-100 uM) for 6-24 hours. The levels of AR and AR-V7 are measured by Western blotting. The DC50 (half-maximal degradation concentration) for AR and AR-V7 is calculated. To measure the effect on cell viability, 22RV1 cells are seeded in 96-well plates (5,000-10,000 cells/well) and treated with varying concentrations of the PROTAC (0.01-100 uM) for 72-96 hours. Cell viability is measured by MTT or CellTiter-Glo, and the IC50 (0.9 uM) is calculated.
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| Animal Protocol |
A typical in vivo protocol for a CRPC degrader would involve a 22RV1 xenograft model. Female BALB/c nude mice (6-8 weeks old) would be subcutaneously injected with 5×10⁶ 22RV1 cells in 0.1 mL of PBS/Matrigel (1:1). When tumors reach an average volume of 100-150 mm3, the mice would be randomized into groups (n=8-10). PROTAC AR/AR-V7 degrader-1 would be formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline) and administered intraperitoneally (IP) or orally (PO) at doses of 10-100 mg/kg daily for 2-3 weeks. Tumor volume would be measured every 2-3 days, and body weight would be monitored.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for PROTAC AR/AR-V7 degrader-1 was not available in the search results. PROTACs are typically larger molecules (MW 485.43) and often exhibit moderate oral bioavailability. Their pharmacokinetic profile can be variable. The compound is soluble in DMSO, as indicated in product specifications. For in vivo studies, it can be formulated in 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline for intraperitoneal administration. No specific half-life (t½), Cmax, or AUC values were reported.
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| Toxicity/Toxicokinetics |
No specific toxicological data for this PROTAC was available in the search results. As a research chemical, standard safety precautions should be followed when handling. This includes wearing appropriate personal protective equipment (PPE) such as gloves, lab coats, and safety goggles. Work should be conducted in a well-ventilated area, such as a chemical fume hood, to avoid inhalation of dust or aerosols. The compound is a PROTAC and should be handled as a potential genotoxicant.
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| References | |
| Additional Infomation |
PROTAC AR/AR-V7 degrader-1 is a research-grade PROTAC that is a dual degrader of AR and AR-V7. It is a chemical tool for studying the role of AR-V7 in resistance to prostate cancer therapies and for validating AR-V7 as a therapeutic target. It is not an FDA-approved drug and is for research use only.
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| Molecular Formula |
C24H19F4N5O2
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| Molecular Weight |
485.43
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| Exact Mass |
485.147
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| CAS # |
2841308-96-9
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| PubChem CID |
162351884
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| Appearance |
Off-white to yellow solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
35
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| Complexity |
872
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1(C(=O)N(C(=O)N1CCNC2=C3C=CC=NC3=C(C=C2)F)C4=CC(=C(C=C4)C#N)C(F)(F)F)C
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| InChi Key |
QMRZVTDYXXBISG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H19F4N5O2/c1-23(2)21(34)33(15-6-5-14(13-29)17(12-15)24(26,27)28)22(35)32(23)11-10-30-19-8-7-18(25)20-16(19)4-3-9-31-20/h3-9,12,30H,10-11H2,1-2H3
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| Chemical Name |
4-[3-[2-[(8-fluoroquinolin-5-yl)amino]ethyl]-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
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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 : ≥ 100 mg/mL (~206.00 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 | 2.0600 mL | 10.3001 mL | 20.6003 mL | |
| 5 mM | 0.4120 mL | 2.0600 mL | 4.1201 mL | |
| 10 mM | 0.2060 mL | 1.0300 mL | 2.0600 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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