Arylisothiocyanato selective androgen receptor modulators (SARMs) for prostate cancer

Dong Jin Hwang, Jun Yang, Huiping Xu, Igor M. Rakov, Michael L. Mohler, James T. Dalton, Duane D. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


A new series of androgen receptor targeted agents (ARTA) was prepared and tested in androgen-dependent and -independent prostate cancer cell lines. These agents were bicalutamide analogs with isothiocyanato substituted B-rings. Also, the linker sulfone of R-bicalutamide was maintained or replaced with several alternative linkages including ether, amine, N-methylamine, thioether, and methylene (in this case the product was a racemic mixture) functional groups at the X-position. To expand the structure-activity relationship (SAR) of these arylisothiocyanato AR ligands, B-ring halogenated arylisothiocyanato ligands were also prepared and tested. The arylisothiocyanato AR ligands showed strong binding affinities to AR ranging from 0.6 to 54 nM. Among them, thioether and ether linkages demonstrated high binding affinities (0.6 and 4.6 nM, respectively) and selective cell growth inhibition (approximately 3- to 6-fold) for LNCaP, an androgen-dependent prostate cancer cell line, when compared to the androgen independent prostate cell lines (DU145, PC-3, and PPC-1) and a bladder cell line (TSU-Pr1). However, the ligands were inactive (IC50>100 mM) in a normal monkey kidney cell line (CV-1) that was used as the control for non-specific toxicity.

Original languageEnglish
Pages (from-to)6525-6538
Number of pages14
JournalBioorganic and Medicinal Chemistry
Issue number19
Publication statusPublished - 1 Oct 2006
Externally publishedYes


  • Androgen receptor (AR)
  • Androgen receptor target agents (ARTA)
  • Bicalutamide
  • Irreversible
  • Isothiocyanate
  • Non-steroidal
  • Prostate cancer (CaP)
  • Selective androgen receptor modulators (SARMs)


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