A novel tamoxifen derivative, ridaifen-F, is a nonpeptidic small-molecule proteasome inhibitor

Makoto Hasegawa, Yukari Yasuda, Makoto Tanaka, Kenya Nakata, Eri Umeda, Yanwen Wang, Chihiro Watanabe, Shoko Uetake, Tatsuki Kunoh, Masafumi Shionyu, Ryuzo Sasaki, Isamu Shiina, Tamio Mizukami

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


In a survey of nonpeptide noncovalent inhibitors of the human 20S proteasome, we found that a novel tamoxifen derivative, RID-F (compound 6), inhibits all three protease activities of the proteasome at submicromolar levels. Structure-activity relationship studies revealed that a RID-F analog (RID-F-S*4, compound 25) is the smallest derivative compound capable of inhibiting proteasome activity, with a potency similar to that of RID-F. Kinetic analyses of the inhibition mode and competition experiments involving biotin-belactosin A (a proteasome inhibitor) binding indicated that the RID-F derivatives interact with the protease subunits in a different manner. Culturing of human cells with these compounds resulted in accumulation of ubiquitinated proteins and induction of apoptosis. Thus, the RID-F derivatives may be useful lead chemicals for the generation of a new class of proteasome inhibitors.

Original languageEnglish
Pages (from-to)290-305
Number of pages16
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - Jan 7 2014


  • Docking studies
  • Proteasome inhibitors
  • Structure-activity relationship (SAR)
  • Tamoxifen derivatives

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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