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)).
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Formule: C38H43F2N7O5S
- Masse moléculaire:747.85
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Stockage:
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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Activité biologique
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Chemical Information
- Protocole
- Pureté et documentation
- Références
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Activité biologique
Description
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 |
|---|---|---|---|---|
| 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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Masse moléculaire 747.85
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Formule 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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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.
Protocole
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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.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
LYA914 Related Classifications
HY-175455 Related Classifications
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