Pin1 and Par14 peptidyl prolyl isomerase inhibitors block cell proliferation

Takafumi Uchida, Mari Takamiya, Morito Takahashi, Hitoshi Miyashita, Hisafumi Ikeda, Toru Terada, Yo Matsuo, Mikako Shirouzu, Shigeyuki Yokoyama, Fumihiro Fujimori, Tony Hunter

Research output: Contribution to journalArticlepeer-review

145 Citations (Scopus)


Disruption of the parvulin family peptidyl prolyl isomerase (PPIase) Pin1 gene delays reentry into the cell cycle when quiescent primary mouse embryo fibroblasts are stimulated with serum. Since Pin1 regulates cell cycle progression, a Pin1 inhibitor would be expected to block cell proliferation. To identify such inhibitors, we screened a chemical compound library for molecules that inhibited human Pin1 PPIase activity in vitro. We found a set of compounds that inhibited Pin1 PPIase activity in vitro with low μM IC50s and inhibited the growth of several cancer lines. Among the inhibitors, PiB, diethyl-1,3,6,8-tetrahydro-1,3,6,8-tetraoxobenzo[lmn][3,8] phenanthroline-2,7-diacetate ethyl 1,3,6,8-tetrahydro-1,3,6,8-tetraoxo-benzo[lmn][3,8] phenanthroline-(2H,7H)-diacetate, had the least nonspecific toxicity. These results suggest that Pin1 inhibitors could be used as a novel type of anticancer drug that acts by blocking cell cycle progression.

Original languageEnglish
Pages (from-to)15-24
Number of pages10
JournalChemistry and Biology
Issue number1
Publication statusPublished - 2003 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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