JZY3032

JYZ3032 is an orally active super inhibitor of androgen receptor ( AR ) and p300/CBP. JYZ3032 redirects the catalytic activity of p300 and locks the complex in a transcriptionally inactive state, thereby inhibiting AR -driven transcription and proliferation. JYZ3032 induces deep and durable tumor regression in castration-resistant and patient-derived xenograft models, and exhibits good tolerability. JYZ3032 can be used in research related to metastatic castration-resistant prostate cancer and prostate cancer ^[1].

In Vivo, JYZ3032 (30 mg/kg; i.p.) induces tumor regression in 75% of castrated male NSG mice bearing VCaP castration-resistant prostate cancer xenografts^[1]. YZ3032 (60 mg/kg; p.o.) also achieves significant tumor inhibition with good tolerance^[1]. JYZ3032 induces complete tumor regression and 100% survival for at least 35 days in NSG mice bearing patient-derived prostate cancer xenografts of MDA-PCa-183, significantly inhibits tumor growth in the MDA-PCa-146-12 model, and exhibits good tolerance^[1].

In Vitro, JYZ3032 (1.0 nM; 120 h) potently inhibits the growth of 22Rv1 prostate cancer cells with an IC₅₀ of 1.0 nM and 69% maximum growth inhibition^[1]. JYZ3032 (100 nM, Serial dilutions; 4 h pulse treatment, total 120 h) exhibits durable, sustained growth inhibitory activity in VCaP and LNCaP prostate cancer cells, with a 4-hour pulse treatment yielding comparable efficacy to continuous exposure^[1]. JYZ3032 potently suppresses enhancer-associated histone acetylation marks in VCaP prostate cancer cells but not in AR-negative Kelly neuroblastoma cells, demonstrating lineage selectivity^[1].

References:
[1]. Luo J, et al. Rewiring Oncogenic Transcriptional Complexes with Domain-ALTeration Chimeras (DALTACs) in Prostate Cancer[J]. bioRxiv, 2026: 2026.04. 24.720638.