BWA-6047
BWA-6047 is an oral active PROTAC degrader targeting AR/AR-V7 and GSPT1 with DC50 values of 3.7, 3.0 and 1.2 nM in 22Rv1 cells. BWA-6047 suppresses the expression of AR downstream target genes and and transcriptional activity. BWA-6047 inhibits cancer cells proliferation, causes G1 phase cell cycle arrest and induces apoptosis. BWA-6047 increases cleaved-PARP-1 and cleaved-caspase-3 levels. BWA-6047 reduces growth of LNCaP xenograft tumors in mice models without obvious toxicity. BWA-6047 can be used for the research of prostate cancer.
(Pink: Androgen Receptor ligand (HY-176129); Blue: Cereblon ligand (HY-W069604); Black: linker (HY-B0236)).
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- Formule: C42H46ClN5O7
- Masse moléculaire:768.30
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Activité biologique
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Cereblon |
PARP-1 |
Caspase 3 |
BWA-6047 (0.01-300 μM; 2-36 h) dose- and time-dependently degrades AR, AR-V7, and GSPT1 in LNCaP, VCaP, and 22Rv1 prostate cancer cells via a CRBN- and proteasome-dependent mechanism (DC50 = 0.6-15.6 nM), with potent activity even in Enzalutamide (HY-70002)-resistant cells[1].
BWA-6047 (0.01-1000000 nM; 72 h) potently inhibits the proliferation of AR-dependent prostate cancer cells, including Enzalutamide-resistant lines, with low activity against AR-independent cancer cells and normal cells[1].
BWA-6047 (0.01-100000 nM; 24 h) potently inhibits the transcriptional activity of wild-type and Enzalutamide-resistant AR mutants (ARW741L, ARF876L) in 293T cells[1].
BWA-6047 (1-100 nM; 24 h) suppresses the expression of AR downstream target genes (PSA, TMPRSS2, FKBP5) in 22Rv1 and LNCaP prostate cancer cells[1].
BWA-6047 (1-30 nM; 24 h) induces G1 phase cell cycle arrest in 22Rv1 prostate cancer cells in a dose-dependent manner[1].
BWA-6047 (1-100 nM; 24 h) induces apoptosis in 22Rv1 and LNCaP prostate cancer cells, as evidenced by increased levels of cleaved apoptotic markers[1].
BWA-6047 (30 nM; 12 h) promotes the polyubiquitination of AR and GSPT1 in 22Rv1 prostate cancer cells, a key step in proteasomal degradation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:22Rv1 and LNCaP prostate cancer cells
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Concentration:1, 3 nM (22Rv1 cells); 10, 30, 100 nM (LNCaP cells)
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Incubation Time:24 h
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Result:Significantly decreased mRNA levels of PSA, TMPRSS2, and FKBP5 at 1 nM and 3 nM in 22Rv1 cells.
Significantly decreased mRNA levels of PSA, TMPRSS2, and FKBP5 at 10 nM, 30 nM, and 100 nM in LNCaP cells.
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Cell Line:22Rv1 prostate cancer cells
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Concentration:1, 3, 10, 30 nM
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Incubation Time:24 h
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Result:Increased G1 phase proportion from 49.7% (control) to 56.3% (1 nM), 55.6% (3 nM), 58.9% (10 nM), and 74.6% (30 nM) in 22Rv1 cells.
Decreased corresponding S phase proportion from 41.4% to 34.1%, 36.6%, 33.4%, and 22.3% in 22Rv1 cells.
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Cell Line:22Rv1 and LNCaP prostate cancer cells
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Concentration:1, 3, 10, 30 μM (22Rv1 cells); 1, 3, 10, 30, 100 μM (LNCaP cells)
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Incubation Time:24 h
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Result:Induced dose-dependent increases in cleaved-PARP-1 and cleaved-caspase-3 levels in 22Rv1 cells.
Induced dose-dependent increases in cleaved-PARP-1 and cleaved-caspase-3 levels in LNCaP cells.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD SCID mice bearing LNCaP xenografts (male, 6 weeks old, castrated after tumor reached ~180 mm3)[1]
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Dosage:20 mg/kg
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Administration:p.o.; daily; 26 days
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Result:Achieved 60.0% tumor growth inhibition (TGI) relative to the vehicle control.
Significantly reduced intratumoral levels of androgen receptor (AR) and G1 to S phase transition 1 (GSPT1) proteins compared to the vehicle control.
Significantly reduced serum prostate-specific antigen (PSA) concentrations compared to the vehicle control.
Showed no observable weight loss in treated mice.
Chemical Information
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Masse moléculaire 768.30
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Formule C42H46ClN5O7
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SMILES
O=C(CCCCCNC1=CC=C2C(N(C3C(NC(CC3)=O)=O)C(C2=C1)=O)=O)N4CCC(CC4)COC5=C(C#N)C=C(C(C)(C6=CC=C(C=C6)OC)C)C=C5Cl
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
BWA-6047 Related Classifications
HY-176128 Related Classifications
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- BWA-6047
- BWA6047
- BWA 6047
- PROTACs
- Androgen Receptor
- Apoptosis
- PARP
- Caspase
- androgen receptor
- normal human liver epithelial cells
- LNCaP xenograft tumors
- CRBN
- prostate cancer cells
- G1 to S phase transition 1
- androgen receptor splice variant 7
- 22Rv1 prostate cancer cells
- enzalutamide-resistant cells
- ubiquitin-proteasome system
- Inhibitor
- inhibitor
- inhibit