2. PROTAC Vitamin D Related/Nuclear Receptor PI3K/Akt/mTOR
  3. PROTACs Androgen Receptor Akt
  4. LYA914

LYA914 is an orally active AR/AR-V7 PROTAC degrader. LYA914 targets the proteolytic degradation of the conserved DNA binding domain (DBD) of the androgen receptor (AR). LYA914 exhibits potent antiproliferative effects in Enzalutamide (HY-70002)-insensitive/resistant cells. LYA914 inhibits tumor growth in VCaP/LNCaP tumor mouse models. LYA914 can be used to study castration-resistant prostate cancer (CRPC). (Pink: AR-DBD ligand-1: HY-175456, Blue: Thalidomide: HY-14658, Pink + Black: AR-DBD ligand-Linker Conjugate 1: HY-175457, Black: Boc-piperidine-oxopiperidin: HY-175458).

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LYA914

LYA914 Chemical Structure

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LYA914 Related Antibodies

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Description

LYA914 is an orally active AR/AR-V7 PROTAC degrader. LYA914 targets the proteolytic degradation of the conserved DNA binding domain (DBD) of the androgen receptor (AR). LYA914 exhibits potent antiproliferative effects in Enzalutamide (HY-70002)-insensitive/resistant cells. LYA914 inhibits tumor growth in VCaP/LNCaP tumor mouse models. LYA914 can be used to study castration-resistant prostate cancer (CRPC). (Pink: AR-DBD ligand-1: HY-175456, Blue: Thalidomide: HY-14658, Pink + Black: AR-DBD ligand-Linker Conjugate 1: HY-175457, Black: Boc-piperidine-oxopiperidin: HY-175458)[1].

IC50 & Target[1]

Cereblon

 

In Vitro

LYA914 (1-10 μM) degrades AR protein in LNCaP cells, 22Rv1 cells with degradation rates of 40.2% and 39.1% at 1 μM, and 82.5% and 84.5% at 10 μM, degrades AR-V7 protein in 22Rv1 cells with degradation rates of 37.4% at 1 μM, and 83.9% at 10 μM[1].
LYA914 (0.01-10 μM, 24 h) enhances the binding of CRBN and AR, and induces the degradation of AR and AR-V7, the DC50s in 22RV1 cells are 0.41 and 0.83 μM, respectively, and the DC50s in vcaP cells are 0.32 and 0.33 μM, respectively, also induces the degradation of AR and AR-V7 in LNCaP cells[1].
LYA914 (24 h) inhibits AR/AR-V7-driven transcriptional activity in overexpressed AR or AR-V7 and the reporter plasmid in 293T cells, with IC50s of 0.19 and 1.29 μM[1].
LYA914 (1-3 μM, 48 h) shows a significant blockade on the AR/AR-V7 signaling pathway by transcriptional inhibition in 22Rv1 cells[1].
LYA914 (5 days) shows antiproliferation activity in LNCaP, VCaP, 22Rv1 cells, with IC50s of 1.21, 1.6, 1.15 μM, shows low cytotoxicity against HL-7702 cells[1].
LYA914 (6 days) remains the antiproliferative effects against LNCaP-EN and VCaP-EN cells with Enzalutamide (HY-70002) exposure, with IC50s of 4.12 and 1.66 μM[1].
LYA914 (24 h) shows significant inhibition on the transcriptional activity of HEK293T cells with AR reporter plasmids are cotransfected with AR (F876L) or AR (W741L) plasmids, respectively, with IC50s of 1.29 and 0.53 μM[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

LYA914 Related Antibodies

Western Blot Analysis[1]

Cell Line: 22Rv1, VCaP and LNCaP cells
Concentration: 0.01 μM, 0.03 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM, 10 μM
Incubation Time: 0 h, 0.167 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 9 h, 11 h, 13 h, 24 h
Result: Induced AR and AR-V7 protein degradation with degradation began at 2 h and reached the maximum level after 13 h, degradation occurred at 6 h and reached maximum degradation at 24 h in AR-positive LNCaP cells.

RT-PCR[1]

Cell Line: 22Rv1 cells
Concentration: 1 μM, 3 μM
Incubation Time: 48 h
Result: Down-regulated the expression of AR targets such as FKBP5, PSA, and TMPRSS2, and AR-V7 targets such as CCNA2, CDC20, and AKT1.
In Vivo

LYA914 (30-100 mg/kg, i.p., once a day, 3 weeks) achieves tumor growth inhibition by down-regulating the expression of the AR protein in the LNCaP tumor model[1].
LYA914 (10-30 mg/kg, p.o., once a day, 16 days) exhibits tumor growth inhibition activity, with particularly notable oral efficacy in the VCaP xenograft model[1].
LYA914 (30-60 mg/kg, p.o., once a day, 14 days) shows no signs of toxicity and is well tolerated in ICR mice[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: LNCaP (1 × 107) tumor NOD SCID mice (6 weeks old) model[1]
Dosage: 30 and 100 mg/kg
Administration: i.p., once a day, 3 weeks
Result: Inhibited tumor growth, the tumor growth inhibition (TGI) rate reaches 83.6% at 100 mg/kg, reduces AR protein levels.
Animal Model: VCaP (1 × 107) tumor NOD SCID mice (6 weeks old) model[1]
Dosage: 10 and 30 mg/kg
Administration: p.o., once a day, 16 days
Result: Inhibited tumor growth, the tumor growth inhibition (TGI) rate reaches 44.5% at 30 mg/kg.
Animal Model: ICR mice (6 weeks old) model[1]
Dosage: 30 and 60 mg/kg
Administration: p.o., once a day, 14 days
Result: Had no obvious weight loss or organ damage, had no change of physiological morphology and function of each organ.
Molecular Weight

747.85

Formula

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
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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LYA914 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

LYA914LYA 914LYA-914PROTACsAndrogen ReceptorAktPKBProtein kinase BPROTACdegraderVCaP cellsLNCaP cellsCRPCICR miceNOD SCID miceInhibitorinhibitorinhibit

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