PROTAC AR Degrader-12
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).
For research use only. We do not sell to patients.
- Formula: C57H76N8O10S
- Molecular Weight:1065.33
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
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ERα |
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.
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | AUC0-∞ | CL | MRT0-t | MRT0-∞ | F |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 % |
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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Molecular Weight 1065.33
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Formula C57H76N8O10S
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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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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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