title: Identification of small-molecule inhibitors of the human S100B-p53 interaction and evaluation of their activity in human melanoma cells.
abstract: The interaction between human S100 calcium-binding protein B (S100B) and the tumor suppressor protein p53 is considered to be a possible therapeutic target for malignant melanoma. To identify potent inhibitors of this interaction, we screened a fragment library of compounds by means of a fluorescence-based competition assay involving the S100B-binding C-terminal peptide of p53. Using active compounds from the fragment library as query compounds, we constructed a focused library by means of two-dimensional similarity searching of a large database. This simple, unbiased method allowed us to identify several inhibitors of the S100B-p53 interaction, and we elucidated preliminary structure-activity relationships. One of the identified compounds had the potential to inhibit the S100B-p53 interaction in melanoma cells.
authors: Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Chihoko
authors: C
authors: Yoshimura
authors: Takamitsu
authors: T
authors: Miyafusa
authors: Kouhei
authors: K
authors: Tsumoto
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D060066:Protein Interaction Maps / Q000187:drug effects; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D009418:S100 Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D009418:S100 Proteins; D054852:Small Molecule Libraries; D016159:Tumor Suppressor Protein p53