title: Identification of a small molecule 1,4-bis-[4-(3-phenoxy-propoxy)-but-2-ynyl]-piperazine as a novel inhibitor of the transcription factor p53.
abstract: OBJECTIVE
  To identify novel small compound inhibitor of p53 protein.
  
  
  METHODS
  Mouse embryonic fibroblasts (MEF) and mouse embryonic stem (ES) cells were tested. Cell proliferation rate was determined using a Cell Proliferation Kit. The mRNA and protein levels of p53-related genes were measured using real-time PCR and Western blotting, respectively. Global response in the p53 signaling network was analyzed using Illumina whole-genome expression BeadChips.
  
  
  RESULTS
  Treatment of MEF cells with a small molecule 1,4-bis-[4-(3-phenoxy-propoxy)-but-2-ynyl]-piperazine (G5) at 10 μmol/L for 24 h markedly reduced the mRNA and protein levels of the p53 downstream genes MDM2 and p21. In G5-treated ES cells, a total of 372 differentially expressed genes were identified, and 18 among them were direct downstream genes of p53; 6 out of 9 p53-repressed genes were upregulated, and 5 out of 9 p53-activated genes were downregulated. In both MEF cells and ES cells, treatment of with G5 (10 μmol/L) up to 48 h neither affected the proliferation rate nor caused morphological alterations.
  
  
  CONCLUSIONS
  G5 inhibits p53 activity and simultaneously preserves the normal growth and proliferation of cells, therefore is a new compound for studies of p53-mediated cell manipulation.
authors.affiliation: Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Man
authors.initials: M
authors.lastname: Tong
authors.forename: Xiu-ying
authors.initials: XY
authors.lastname: Liu
authors.forename: Guan-zheng
authors.initials: GZ
authors.lastname: Luo
authors.forename: Dong-fang
authors.initials: DF
authors.lastname: Xie
authors.forename: Shao-fang
authors.initials: SF
authors.lastname: Ren
authors.forename: Dong-hui
authors.initials: DH
authors.lastname: Bai
authors.forename: Liu
authors.initials: L
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.forename: Xiu-jie
authors.initials: XJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010647:Phenyl Ethers / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C585407:1,4-bis(4-(3-phenoxypropoxy)but-2-ynyl)piperazine; D010647:Phenyl Ethers; D010879:Piperazines; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53