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Related Experiment Video

Updated: Jan 19, 2026

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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A Novel Small Molecule Targets Androgen Receptor and Its Splice Variants in Castration-Resistant Prostate Cancer.

Zhenyu Yang1,2,3, Dan Wang3, James K Johnson4

  • 1Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P.R. China.

Molecular Cancer Therapeutics
|September 27, 2019
PubMed
Summary

A new drug, JJ-450, effectively inhibits androgen receptor (AR) activity and targets AR splice variants. This shows promise for treating castration-resistant prostate cancer (CRPC), even when resistant to other therapies.

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Murine Prostate Micro-dissection and Surgical Castration
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Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Androgen receptor (AR) reactivation drives castration-resistant prostate cancer (CRPC) resistance to antiandrogens.
  • Novel small molecules targeting AR and its splice variants like ARv7 are needed for CRPC treatment.
  • Previous research identified a lead compound, IMTPPE, inhibiting AR in CRPC cells.

Purpose of the Study:

  • To investigate JJ-450, a novel analogue of IMTPPE, as a potential therapeutic agent for CRPC.
  • To evaluate JJ-450's direct and specific inhibition of AR transcriptional activity and ARv7.
  • To assess JJ-450's efficacy in suppressing CRPC tumor xenograft growth.

Main Methods:

  • Pulldown assay, RNA-sequencing, PSA-based luciferase, qPCR, and chromatin immunoprecipitation assays were used.
  • A 22Rv1 xenograft tumor model was employed to evaluate in vivo efficacy.
  • JJ-450's effect on AR recruitment to androgen-responsive elements and target gene expression was assessed.

Main Results:

  • JJ-450 directly and specifically inhibits AR transcriptional activity and ARv7.
  • JJ-450 blocks AR recruitment to androgen-responsive elements and suppresses AR target gene expression.
  • JJ-450 significantly suppresses the growth of CRPC tumor xenografts, including ARv7-expressing models.

Conclusions:

  • JJ-450 represents a new class of AR antagonists.
  • JJ-450 demonstrates therapeutic potential for CRPC, including enzalutamide-resistant cases.
  • JJ-450 effectively targets both AR and ARv7, offering a novel treatment strategy.