PROTAC AR Degrader-12
Based on 1 Customer Validation
PROTAC AR Degrader-12 is a highly efficient PROTAC targeting AR coactivator binding site (AR-CBS). PROTAC AR Degrader-12 induces AR degradation in a ubiquitin proteasome system (UPS) pathway-dependent manner. PROTAC AR Degrader-12 inhibits tumor cell growth by affecting DNA replication and cell division PROTAC AR Degrader-12 could not only effectively degrade AR, but also potently inhibit the proliferation of MCF-7 and multiple mutant or resistant BC cells. PROTAC AR Degrader-12 effectively blocked estrogen receptor α (ERα) signaling through a dual mechanism involving ERα protein downregulation and suppression of its transcriptional activity. PROTAC AR Degrader-12 significantly inhibits the mRNA expression of FOXA1, GREB1, SRC, and PELP1. PROTAC AR Degrader-12 can be used for the study of breast cancer.
(Pink: AR ligand (HY-179442); Blue: VHL ligand (HY-112078); Black: linker).
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté : 98.52%
- Formule: C57H76N8O10S
- Masse moléculaire:1065.33
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Stockage: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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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
IC50 & Target
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ERα |
In Vitro
PROTAC AR Degrader-12 (Compound 18o) shows good inhibitory activity against MCF-7 (IC50 = 0.13 μM) and LCC2 cells(IC50 = 0.54 μM) and exhibits broad-spectrum efficacy against clinically relevant mutant variants, demonstrating potent submicromolar inhibition of MCF-7D538G(IC50 = 0.66 μM), MCF-7Y537S (IC50 = 0.44 μM), and MCF-7EGFR(IC50 =0.52 μM)[1].
PROTAC AR Degrader-12 (0.01-2 μM, 24 h) effectively and in a dose-dependent manner degrades AR protein in MCF-7 cells (DC50 = 0.72 μM)[1].
PROTAC AR Degrader-12 (1 μM, 0-24 h) shows a time-dependent effect on AR degradation in MCF-7 cells[1].
PROTAC AR Degrader-12 (0.01-2 μM, 24 h) causes a concentration-dependent downregulation of ERα protein in MCF-7 cells[1].
PROTAC AR Degrader-12 (0.01-2 μM, 12-24 h) significantly downregulates ERα protein in MCF-7D538G, MCF-7Y537S, MCF-7EGFR, LCC2, and T47D cells, and fails to downregulate ERβ protein in PC9 cells[1].
PROTAC AR Degrader-12 (1 μM, 24 h) induces a decrease in ERα through an indirect mechanism, rather than by directly targeting the degradation of CBS in MCF-7 cells[1].
PROTAC AR Degrader-12 (0-5 μM, 0-24 h) reduces AR protein in MCF-7 cells due to posttranscriptional degradation, while the reduction in ERα was a result of transcriptional repression[1].
PROTAC AR Degrader-12 exhibits potent antiproliferative activity in AR-overexpressing but ERα-deficient prostate cancer cells LNCaP (IC50 = 0.46 μM), while its antiproliferative activity is significantly reduced in AR-negative MDA-MB-231 cells (IC50 > 30 μM)[1].
PROTAC AR Degrader-12 was very effective in stabilizing the AR protein at high temperature, while it only displays a weak protective effect on ERα protein, suggesting that compound PROTAC AR Degrader-12 engages AR but does not bind to Erα in LCC2 cells[1].
PROTAC AR Degrader-12 (1 μM, 24 h) significantly inhibits the mRNA expression of FOXA1, GREB1, SRC, and PELP1 in MCF-7 cells[1].
PROTAC AR Degrader-12 (1-10 μM, 48 h) induces S-phase cell cycle arrest in MCF-7 and LCC2 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MCF-7 cells
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Concentration:0.01 μM, 0.1 μM, 1 μM, 2 μM
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Incubation Time:0 h, 3 h, 6 h, 12 h, 18 h, 24 h
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Result:Effectively and in a dose-dependent manner degraded AR protein.
Time-dependent effect on AR degradation.
Caused a concentration-dependent downregulation of ERα protein.
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Cell Line:MCF-7 cells
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Concentration:0 μM, 1 μM, 5 μM
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Incubation Time:0 h, 4 h, 24 h
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Result:AR mRNA expression increased significantly with increasing concentration; ERα mRNA expression was downregulated.
The expression of ERα target genes (TFF1, PGR) and AR target genes (PSA, TMPRSS2) was significantly suppressed after 24 hours.
Significantly inhibited the mRNA expression of FOXA1, GREB1, SRC, and PELP1.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | AUC0-∞ | CL | MRT0-t | MRT0-∞ | F |
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| Rat | 2 mg/kg | i.v. | 28.5 h | 0.11 h | 639.02 ng/mL | 514 ng·h/mL | 545.39 ng·h/mL | 760.12 mL/h/kg | 2.97 h | 10.20 h | / |
| Rat | 20 mg/kg | p.o. | 38.53 h | 1.08 h | 2.69 ng/mL | 43.70 ng·h/mL | 105.74 ng·h/mL | 40313.87 mL/h/kg | 20.92 h | 89.95 h | 1.94 % |
| Rat | 4 mg/kg | i.p. | 14.18 h | 0.39 h | 31.19 ng/mL | 85.74 ng·h/mL | 91.28 ng·h/mL | 8800.82 mL/h/kg | 12.13 h | 15.52 h | 16.74 % |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Balb/c nude mice (female, 4 weeks old) were subcutaneously injected with MCF-7 human breast cancer cells (5 × 106 cells)[1].
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Dosage:5 μM/kg, 10 μM/kg
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Administration:I.p., once every other day
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Result:At a dose of 10 μM/kg, it significantly inhibited tumor growth.
Tumor volume decreased, and Ki67 proliferation marker expression was reduced.
AR and ERα protein levels were downregulated in tumor tissue.
No significant change in body weight or significant toxicity was observed.
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Animal Model:Balb/c nude mice (female, 4 weeks old) were subcutaneously injected with tamoxifen-resistant LCC2 human breast cancer cells (5 × 106 cells)[1].
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Dosage:5 μM/kg, 10 μM/kg
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Administration:I.p., once every other day
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Result:Tumor growth inhibition rate (TGI) reached 58% at a dose of 10 μM/kg.
Ki67 expression was decreased, and AR and ERα proteins were downregulated.
Body weight remained stable, with no signs of toxicity.
Chemical Information
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Appearance Solid
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Masse moléculaire 1065.33
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Formule C57H76N8O10S
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Color Off-white to light yellow
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SMILES
CC(COC1=C(C=CC(C(N2CCC(CN3CCCC(C(N[C@@H](C(C)(C)C)C(N4[C@H](C(N[C@H](C5=CC=C(C6=C(C)N=CS6)C=C5)C)=O)C[C@@H](O)C4)=O)=O)C3)CC2)=O)=C1)NC(C7=CC(OCC(C)C)=C(C=C7)[N+]([O-])=O)=O)C
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
In Vitro:
DMSO : 100 mg/mL (93.87 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureté et documentation
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Fiche technique (283 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instruction de manipulation (2659 KB)
Références
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 |
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| DMSO | 1 mM | 0.9387 mL | 4.6934 mL | 9.3868 mL | 23.4669 mL |
| 5 mM | 0.1877 mL | 0.9387 mL | 1.8774 mL | 4.6934 mL | |
| 10 mM | 0.0939 mL | 0.4693 mL | 0.9387 mL | 2.3467 mL | |
| 15 mM | 0.0626 mL | 0.3129 mL | 0.6258 mL | 1.5645 mL | |
| 20 mM | 0.0469 mL | 0.2347 mL | 0.4693 mL | 1.1733 mL | |
| 25 mM | 0.0375 mL | 0.1877 mL | 0.3755 mL | 0.9387 mL | |
| 30 mM | 0.0313 mL | 0.1564 mL | 0.3129 mL | 0.7822 mL | |
| 40 mM | 0.0235 mL | 0.1173 mL | 0.2347 mL | 0.5867 mL | |
| 50 mM | 0.0188 mL | 0.0939 mL | 0.1877 mL | 0.4693 mL | |
| 60 mM | 0.0156 mL | 0.0782 mL | 0.1564 mL | 0.3911 mL | |
| 80 mM | 0.0117 mL | 0.0587 mL | 0.1173 mL | 0.2933 mL |
PROTAC AR Degrader-12 Related Classifications
HY-179433 Related Classifications
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