PROTAC AR Degrader-8
Based on 1 Customer Validation
PROTAC AR Degrader-8 is the PROTAC degrader for androgen receptor (AR) that degrades AR-FL with DC50s of 0.018 μM and 0.14 μM in 22Rv1 cell and LNCaP cell, degrades AR-V7 with DC50 of 0.026 μM in 22Rv1 cell. PROTAC AR Degrader-8 inhibits the proliferation of cancer cell 22Rv1 and LNCaP with IC50 values of 0.038 μM and 1.11 μM. PROTAC AR Degrader-8 arrests cell cycle at G2/M phase, induces apoptosis in 22Rv1 cell. PROTAC AR Degrader-8 exhibits anticancer efficacy in mouse and zebrafish model. PROTAC AR Degrader-8 can be used for the research of prostate cancer, castration-resistant prostate cancer.
(Pink: Androgen Receptor ligand (HY-170330); Blue: Cereblon ligand (HY-14658); Black: linker).
연구목적의 판매만을 진행합니다. 환자를 대상으로 한 판매는 하지 않습니다.
- Purity : 99.98%
- CAS No.: 3044108-04-2
- 화학식: C40H41N5O7
- 분자량:703.78
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- Protocol
- 순도&문서
- References
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Help & FAQs
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Biological Activity
제품 설명
In Vitro
PROTAC AR Degrader-8 (NP18) (0.01-100 μM; 4 days) potently inhibits the viability of AR-dependent prostate cancer 22Rv1 and LNCaP cells with IC50 values of 0.038 μM and 0.176 μM respectively, while showing weak activity against AR-independent and normal epithelial cells[1].
PROTAC AR Degrader-8 (0.001-5 μM; 1 μM; 0-24 h) induces potent, time- and dose-dependent degradation of AR-FL in LNCaP cells (DC50 = 0.14 μM) and both AR-FL (DC50 = 0.018 μM) and AR-V7 (DC50 = 0.026 μM) in 22Rv1 cells[1].
PROTAC AR Degrader-8 (100 nM; 24 h) reduces nuclear localization and expression of both AR-FL and AR-V7 in 22Rv1 cells[1].
PROTAC AR Degrader-8 (100-500 nM; 24 h) blocks the AR/AR-V7 signaling pathway in 22Rv1 cells by suppressing target gene expression without altering AR mRNA levels[1].
PROTAC AR Degrader-8 (100 nM; 12 h) induces AR-FL and AR-V7 degradation in 22Rv1 cells via a CRBN-dependent ubiquitin-proteasome system[1].
PROTAC AR Degrader-8 (0.001-5 μM; 24 h) selectively degrades AR-FL and AR-V7 in 22Rv1 cells without affecting homologous nuclear receptor proteins[1].
PROTAC AR Degrader-8 (1-100 nM; 14 days) potently inhibits long-term colony formation of 22Rv1 prostate cancer cells in a dose-dependent manner[1].
PROTAC AR Degrader-8 (100-500 nM; 48 h) dose-dependently induces apoptosis in 22Rv1 prostate cancer cells, with apoptosis rates of 26.86% at 100 nM and 32.51% at 500 nM[1].
PROTAC AR Degrader-8 (100-500 nM; 24 h) induces G2/M phase cell cycle arrest in 22Rv1 prostate cancer cells, with 15.45% and 21.54% of cells in G2/M at 100 nM and 500 nM respectively[1].
PROTAC AR Degrader-8 (0.1-10 μM) has an excellent hERG safety profile, with minimal inhibition of hERG channels even at 10 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:22Rv1, LNCaP, DU-145, RWPE-1, MCF-10A
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Concentration:0.01 μM; 0.1 μM; 1 μM; 10 μM; 100 μM
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Incubation Time:4 days
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Result:Inhibited 22Rv1 cell viability with an IC50 of 0.038 μM.
Inhibited LNCaP cell viability with an IC50 of 0.176 μM.
Showed IC50 values >80 μM for DU-145, RWPE-1, and MCF-10A cells.
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Cell Line:22Rv1
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Concentration:100 nM
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Incubation Time:24 h
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Result:Caused a significant decrease in both nuclear localization and expression levels of AR-FL and AR-V7.
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Cell Line:22Rv1
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Concentration:100 nM, 500 nM
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Incubation Time:24 h
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Result:Dose-dependently suppressed the expression of PSA, TMPRSS2, KLK2, and UBE2C genes.
Showed no significant alteration of AR mRNA levels at either 100 nM or 500 nM concentration.
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Cell Line:22Rv1
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Concentration:100 nM
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Incubation Time:12 h
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Result:Had its induced degradation of AR-FL and AR-V7 significantly blocked by nNP18, thalidomide, MLN4924, and MG132.
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Cell Line:22Rv1
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Concentration:0.001 μM, 0.005 μM, 0.01 μM, 0.05 μM, 0.1 μM, 0.5 μM, 1 μM, 5 μM
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Incubation Time:24 h
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Result:Showed no obvious degradation of ERα, GR, PR, or PPARγ at concentrations effective for AR-FL and AR-V7 degradation.
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Cell Line:22Rv1
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Concentration:1, 10, 100 nM
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Incubation Time:14 days
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Result:Dose-dependently reduced colony formation of 22Rv1 cells, with a significant reduction at 100 nM.
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Cell Line:22Rv1
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Concentration:100 nM, 500 nM
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Incubation Time:48 h
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Result:Induced apoptosis in 22Rv1 cells at a rate of 26.86% (100 nM) and 32.51% (500 nM).
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Cell Line:22Rv1
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Concentration:100 nM, 500 nM
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Incubation Time:24 h
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Result:Increased accumulation of 22Rv1 cells in the G2/M phase, with percentages of 15.45% (100 nM) and 21.54% (500 nM) compared to 8.61% in the vehicle group.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | AUC0-∞ | MRT0-t | MRT0-∞ | C0 | Vss | Vz | CL |
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| Rat[1] | 2 mg/kg | i.v. | 2.64 h | 0.083 h | 6443.30 ng/mL | 2208.53 ng·h/mL | 2220.92 ng·h/mL | 0.54 h | 0.62 h | 13935.03 ng/mL | 571.03 mL/kg | 3570.81 mL/kg | 904.46 mL/h/kg |
In Vivo
PROTAC AR Degrader-8 (25-50 ng per zebrafish; yolk sac injection) exerts a dose-dependent inhibitory effect on prostate cancer patient-derived xenografts in zebrafish, with near-complete ablation of tumor fluorescence at the 50 ng dose[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c-nu nude mice (male, 6-8 weeks old, 18-22 g) injected with 22Rv1 cells[1]
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Dosage:10 mg/kg
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Administration:i.p.; once daily; 21 days
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Result:Reduced tumor growth rate to 67% of control levels.
Significantly degraded AR-FL and AR-V7 proteins in tumor tissue.
Caused no marked pathological damage in heart, liver, spleen, lung, or kidney tissues.
Increased mouse body weight steadily during treatment.
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Annexin V plus membrane-impermeant dye apoptosis staining
- BrdU Incorporation Assay
- Research Protocol for Endocrine Diseases
- How to Select a Suitable Non-Mouse Animal Model
- Apoptosis Solutions
- Protocol for Cell Cycle
- Cell Viability Determination by MTT Colorimetric Assay
- How to Choose the Right Model Animal
Chemical Information
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CAS No. 3044108-04-2
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Appearance Solid
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분자량 703.78
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화학식 C40H41N5O7
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Color Light yellow to yellow
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SMILES
O=C1N(C(CC2)C(NC2=O)=O)C(C3=C1C=CC=C3NCCOC4=CC=C(C(C)(C5=CC=C(OCC6=NC(N7CCOCC7)=CC=C6)C=C5)C)C=C4)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
In Vitro:
DMSO : ≥ 100 mg/mL (142.09 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
순도&문서
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Data Sheet (282 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.4209 mL | 7.1045 mL | 14.2090 mL | 35.5225 mL |
| 5 mM | 0.2842 mL | 1.4209 mL | 2.8418 mL | 7.1045 mL | |
| 10 mM | 0.1421 mL | 0.7104 mL | 1.4209 mL | 3.5522 mL | |
| 15 mM | 0.0947 mL | 0.4736 mL | 0.9473 mL | 2.3682 mL | |
| 20 mM | 0.0710 mL | 0.3552 mL | 0.7104 mL | 1.7761 mL | |
| 25 mM | 0.0568 mL | 0.2842 mL | 0.5684 mL | 1.4209 mL | |
| 30 mM | 0.0474 mL | 0.2368 mL | 0.4736 mL | 1.1841 mL | |
| 40 mM | 0.0355 mL | 0.1776 mL | 0.3552 mL | 0.8881 mL | |
| 50 mM | 0.0284 mL | 0.1421 mL | 0.2842 mL | 0.7104 mL | |
| 60 mM | 0.0237 mL | 0.1184 mL | 0.2368 mL | 0.5920 mL | |
| 80 mM | 0.0178 mL | 0.0888 mL | 0.1776 mL | 0.4440 mL | |
| 100 mM | 0.0142 mL | 0.0710 mL | 0.1421 mL | 0.3552 mL |
PROTAC AR Degrader-8 Related Classifications
HY-170329 Related Classifications
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Keywords
- PROTAC AR Degrader-8
- 3044108-04-2
- PROTAC AR Degrader8
- PROTAC AR Degrader 8
- PROTACs
- Androgen Receptor
- Apoptosis
- LNCaP cells
- patient-derived xenograft models
- CRBN-dependent ubiquitin-proteasome system
- full-length androgen receptor
- androgen receptor
- prostate cancer
- castration-resistant prostate cancer
- xenograft models
- androgen receptor splice variant 7
- 22Rv1 cells
- Inhibitor
- inhibitor
- inhibit