LYA914
LYA914 is an orally effective AR/AR-V7 PROTAC degrader. LYA914 recruits CRBN to target and bind the conserved DBD domain of AR and AR-V7, inducing their ubiquitination and subsequent degradation, thereby completely blocking AR signaling and transcriptional activity. LYA914 can be used for the research of castration-resistant prostate cancer.
(Pink: AR-DBD ligand (HY-175456); Blue: Cereblon ligand (HY-14658); Black: linker (HY-175458)).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Fòrmula: C38H43F2N7O5S
- Peso molecular:747.85
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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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Actividad biológica
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Chemical Information
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
AR-V7 0.32 μM (DC50, 22Rv1) |
AR-V7 0.33 μM (DC50, VCaP) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| 22Rv1 | DC50 |
0.41 μM
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Half-maximal degradation of androgen receptor (AR) in human 22Rv1 prostate cancer cells incubated for 24 h, measured via Western blot analysis.
Half-maximal degradation of androgen receptor (AR) in human 22Rv1 prostate cancer cells incubated for 24 h, measured via Western blot analysis.
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40721349 |
| 22Rv1 | DC50 |
0.32 μM
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Half-maximal degradation of androgen receptor splice variant AR-V7 in human 22Rv1 prostate cancer cells incubated for 24 h, measured via Western blot analysis.
Half-maximal degradation of androgen receptor splice variant AR-V7 in human 22Rv1 prostate cancer cells incubated for 24 h, measured via Western blot analysis.
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40721349 |
| VCaP | DC50 |
0.83 μM
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Half-maximal degradation of androgen receptor (AR) in human VCaP prostate cancer cells incubated for 24 h, measured via Western blot analysis.
Half-maximal degradation of androgen receptor (AR) in human VCaP prostate cancer cells incubated for 24 h, measured via Western blot analysis.
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40721349 |
| VCaP | DC50 |
0.33 μM
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Half-maximal degradation of androgen receptor splice variant AR-V7 in human VCaP prostate cancer cells incubated for 24 h, measured via Western blot analysis.
Half-maximal degradation of androgen receptor splice variant AR-V7 in human VCaP prostate cancer cells incubated for 24 h, measured via Western blot analysis.
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40721349 |
| HEK-293T | IC50 |
0.19 μM
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Half-maximal inhibition of androgen receptor (AR)-driven transcriptional activity in engineered human HEK293T cells (transfected with AR and PSA reporter plasmids) incubated for 24 h with 0.1 nM R1881, measured via PSA promoter luciferase reporter assay.
Half-maximal inhibition of androgen receptor (AR)-driven transcriptional activity in engineered human HEK293T cells (transfected with AR and PSA reporter plasmids) incubated for 24 h with 0.1 nM R1881, measured via PSA promoter luciferase reporter assay.
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40721349 |
| HEK-293T | IC50 |
1.29 μM
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Half-maximal inhibition of androgen receptor splice variant AR-V7-driven transcriptional activity in engineered human HEK293T cells (transfected with AR-V7 and PSA reporter plasmids) incubated for 24 h with 0.1 nM R1881, measured via PSA promoter luciferase reporter assay.
Half-maximal inhibition of androgen receptor splice variant AR-V7-driven transcriptional activity in engineered human HEK293T cells (transfected with AR-V7 and PSA reporter plasmids) incubated for 24 h with 0.1 nM R1881, measured via PSA promoter luciferase reporter assay.
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40721349 |
| LNCaP | IC50 |
1.21 μM
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Half-maximal inhibition of human LNCaP prostate cancer cell proliferation incubated for 5 days in 5% charcoal-stripped medium with 0.1 nM R1881, measured via CCK-8 assay.
Half-maximal inhibition of human LNCaP prostate cancer cell proliferation incubated for 5 days in 5% charcoal-stripped medium with 0.1 nM R1881, measured via CCK-8 assay.
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40721349 |
| VCaP | IC50 |
1.61 μM
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Half-maximal inhibition of human VCaP prostate cancer cell proliferation incubated for 5 days in 5% charcoal-stripped medium with 0.1 nM R1881, measured via CCK-8 assay.
Half-maximal inhibition of human VCaP prostate cancer cell proliferation incubated for 5 days in 5% charcoal-stripped medium with 0.1 nM R1881, measured via CCK-8 assay.
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40721349 |
| 22Rv1 | IC50 |
1.15 μM
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Half-maximal inhibition of human 22Rv1 enzalutamide-resistant prostate cancer cell proliferation incubated for 5 days in medium with 10% fetal bovine serum, measured via CCK-8 assay.
Half-maximal inhibition of human 22Rv1 enzalutamide-resistant prostate cancer cell proliferation incubated for 5 days in medium with 10% fetal bovine serum, measured via CCK-8 assay.
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40721349 |
| LNCaP | IC50 |
4.12 μM
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Half-maximal inhibition of human LNCaP-EN enzalutamide-resistant prostate cancer cell proliferation incubated for 6 days in 5% charcoal-stripped medium with 0.1 nM R1881, measured via CellTiter-Lumi luminescent cell viability assay.
Half-maximal inhibition of human LNCaP-EN enzalutamide-resistant prostate cancer cell proliferation incubated for 6 days in 5% charcoal-stripped medium with 0.1 nM R1881, measured via CellTiter-Lumi luminescent cell viability assay.
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40721349 |
| LNCaP | IC50 |
1.66 μM
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Half-maximal inhibition of human VCaP-EN enzalutamide-resistant prostate cancer cell proliferation incubated for 6 days in 5% charcoal-stripped medium with 0.1 nM R1881, measured via CellTiter-Lumi luminescent cell viability assay.
Half-maximal inhibition of human VCaP-EN enzalutamide-resistant prostate cancer cell proliferation incubated for 6 days in 5% charcoal-stripped medium with 0.1 nM R1881, measured via CellTiter-Lumi luminescent cell viability assay.
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40721349 |
In Vitro
LYA914 (0.01-10 μM; 24 h) potently degrades AR (DC50 = 0.41 μM) and AR-V7 (DC50 = 0.32 μM) in a dose-dependent manner in 22Rv1 prostate cancer cells, and potently degrades AR (DC50 = 0.83 μM) and AR-V7 (DC50 = 0.33 μM) in a dose-dependent manner in VCaP prostate cancer cells[1].
LYA914 (3 μM; 2-24 h) induces time-dependent degradation of AR in LNCaP cells, with degradation initiating at 6 h and reaching the maximum degradation rate at 24 h[1].
LYA914 (1 μM; 12 h) enhances the binding of CRBN to AR and promotes AR ubiquitination in 22Rv1 cells pre-treated with MG132 (HY-13259)[1].
LYA914 (24 h) potently inhibits AR- and AR-V7-driven transcriptional activity in 293T cells overexpressing AR or AR-V7[1].
LYA914 (1-3 μM; 48 h) significantly downregulates the mRNA expression of AR-regulated genes and AR-V7-regulated genes in 22Rv1 cells[1].
LYA914 (4-6 days) inhibits the viability of LNCaP (IC50 = 1.21 μM), 22Rv1 (IC50 = 1.15 μM), LNCaP-EN (IC50 = 4.12 μM) and VCaP-EN (IC50 = 1.66 μM) cells in a concentration-dependent manner, and exhibits extremely low toxicity to the human normal liver tissue cell line HL-7702 (IC50 > 30 μM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:22Rv1, VCaP
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Concentration:0.01, 0.03, 0.1, 0.3, 1, 3, 10 μM
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Incubation Time:0.167, 0.5, 1, 2, 4, 6, 9, 11, 13, 24 h
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Result:Degraded AR and AR-V7 proteins in a concentration-dependent manner.
Induced the degradation of target proteins in a time-dependent manner.
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Cell Line:22Rv1
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Concentration:1 μM, 3 μM
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Incubation Time:48 h
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Result:Dose-dependently downregulated the mRNA expression levels of AR target genes and AR-V7 target genes.
Parmacokinetics
In Vivo
LYA914 (10-30 mg/kg; p.o.; once daily; for 16 days) exhibits significant oral antitumor growth activity and is well tolerated in the BALB/c nude mouse model bearing VCaP cell xenografts[1].
LYA914 (30-60 mg/kg; p.o.; once daily; for 14 days) exhibits a safe profile without significant body weight loss or organ damage in the ICR mouse in vivo toxicity model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD-SCID (6 weeks old)[1]
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Dosage:30 mg/kg; 100 mg/kg
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Administration:i.p.; once daily; 21 days
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Result:Inhibited tumor growth in a dose-dependent manner.
Reached a tumor growth inhibition (TGI) rate of 83.6% at 100 mg/kg.
Caused no significant change in mouse body weight during treatment.
Reduced AR protein levels in tumor tissue notably.
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Animal Model:NOD-SCID (6 weeks old)[1]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:p.o.; once daily; 16 days
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Result:Showed no significant efficacy at 10 mg/kg.
Inhibited tumor growth obviously with a TGI rate of 44.5% at 30 mg/kg.
Caused no significant mouse body weight loss during treatment.
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Animal Model:ICR (6 weeks old)[1]
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Dosage:30 mg/kg; 60 mg/kg
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Administration:p.o.; daily; 14 days
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Result:Caused no significant body weight loss or organ damage at either dose.
Resulted in normal physiological morphology and function of all examined organs as shown by H&E staining.
Chemical Information
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Peso molecular 747.85
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Fòrmula C38H43F2N7O5S
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SMILES
O=C1N(C(CC2)C(NC2=O)=O)C(C3=C1C=CC(N4CCC(CN5CCC(N6CCN(C7=NC(C8=CC=C(F)C(F)=C8OC)=CS7)CC6)CC5)CC4)=C3)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocolo
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Dual Luciferin reporter gene assay
Luciferin reporter gene assay is a reporting system to detect the activity of Firefly Luciferase using luciferin as a substrate, which is often used in the research of miRNA target gene verification and promoter transcriptive activity regulation. Dual luciferase usually refers to Firefly luciferase and Renilla luciferase.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
LYA914 Related Classifications
HY-175455 Related Classifications
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