Art. -Nr.: HY-175455

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)).

Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.

Formel: C₃₈H₄₃F₂N₇O₅S
Molecular Weight:747.85

Speicherung:

Please store the product under the recommended conditions in the Certificate of Analysis.

Data Sheet (280 KB)

LYA914 Chemical Structure

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Preis

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Menge

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Use of MCE Products

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Reinheit & Dokumentation
Verweise
Calculators
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

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^[1]. (Pink: AR-DBD ligand (HY-175456); Blue: Cereblon ligand (HY-14658); Black: linker (HY-175458)).

IC₅₀ & Target

^[1]

AR-V7

0.32 μM (DC₅₀, 22Rv1)

AR-V7

0.33 μM (DC₅₀, VCaP)

Alle PROTACs Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
22Rv1	DC₅₀	0.41 μM	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.	40721349
22Rv1	DC₅₀	0.32 μM	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.	40721349
VCaP	DC₅₀	0.83 μM	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.	40721349
VCaP	DC₅₀	0.33 μM	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.	40721349
HEK-293T	IC₅₀	0.19 μM	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.	40721349
HEK-293T	IC₅₀	1.29 μM	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.	40721349
LNCaP	IC₅₀	1.21 μM	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.	40721349
VCaP	IC₅₀	1.61 μM	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.	40721349
22Rv1	IC₅₀	1.15 μM	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.	40721349
LNCaP	IC₅₀	4.12 μM	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.	40721349
LNCaP	IC₅₀	1.66 μM	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.	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.

Western Blot Analysis^[1]

Cell Line:

22Rv1, VCaP
Concentration:

0.01, 0.03, 0.1, 0.3, 1, 3, 10 μM
Incubation Time:

0.167, 0.5, 1, 2, 4, 6, 9, 11, 13, 24 h
Result:

Degraded AR and AR-V7 proteins in a concentration-dependent manner.
Induced the degradation of target proteins in a time-dependent manner.

Real Time qPCR^[1]

Cell Line:

22Rv1
Concentration:

1 μM, 3 μM
Incubation Time:

48 h
Result:

Dose-dependently downregulated the mRNA expression levels of AR target genes and AR-V7 target genes.

Parmacokinetics

Species	Dose	Route	T_1/2	T_max	C_max	AUC_0-t	F
Mice^[1]	2 mg/kg	i.v.	3.3 h	0.083 h	66 ng/mL	568 ng·h/mL	/
Mice^[1]	30 mg/kg	i.p.	6.5 h	0.375 h	534 ng/mL	5906 ng·h/mL	51.2 %
Mice^[1]	30 mg/kg	p.o.	14.7 h	5.3 h	305 ng/mL	7631 ng·h/mL	65.9 %

In Vivo

LYA914 (30-100 mg/kg; i.p.; once daily; 3 weeks) inhibits tumor growth in a dose-dependent manner without obvious toxic and side effects in the NOD SCID mouse model bearing LNCaP cell xenografts ^[1].
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.

Animal Model:

NOD-SCID (6 weeks old)^[1]
Dosage:

30 mg/kg; 100 mg/kg
Administration:

i.p.; once daily; 21 days
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.

Animal Model:

NOD-SCID (6 weeks old)^[1]
Dosage:

10 mg/kg; 30 mg/kg
Administration:

p.o.; once daily; 16 days
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.

Animal Model:

ICR (6 weeks old)^[1]
Dosage:

30 mg/kg; 60 mg/kg
Administration:

p.o.; daily; 14 days
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

Molecular Weight 747.85
Formel C₃₈H₄₃F₂N₇O₅S
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
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

Please store the product under the recommended conditions in the Certificate of Analysis.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (280 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Lv Y, et al. Discovery of LYA914, An Orally Bioavailable PROTAC Degrader Targeting the DNA Binding Domain of the Androgen Receptor for the Treatment of CRPC. Journal of medicinal chemistry. 2025 Aug 14;68(15):16593-16612. [Content Brief]

Calculators

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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LYA914

Alle PROTACs Isoform-spezifische Produkte anzeigen