title: Morphobase, an encyclopedic cell morphology database, and its use for drug target identification.
abstract: Visual observation is a powerful approach for screening bioactive compounds that can facilitate the discovery of attractive druggable targets following their chemicobiological validation. So far, many high-content approaches, using sophisticated imaging technology and bioinformatics, have been developed. In our study, we aimed to develop a simpler method that focuses on intact cell images because we found that dynamic changes in morphology are informative, often reflecting the mechanism of action of a drug. Here, we constructed a chemical-genetic phenotype profiling system, based on the high-content cell morphology database Morphobase. This database compiles the phenotypes of cancer cell lines that are induced by hundreds of reference compounds, wherein those of well-characterized anticancer drugs are classified by mode of action. Furthermore, we demonstrate the applicability of this system in identifying NPD6689, NPD8617, and NPD8969 as tubulin inhibitors.
authors.affiliation: Chemical Biology Core Facility, Chemical Biology Department, RIKEN Advanced Science Institute, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Futamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawatani
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kazami
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Muroi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimizu
authors.forename: Koji
authors.initials: K
authors.lastname: Tomita
authors.forename: Nobumoto
authors.initials: N
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003584:Cytological Techniques / Q000379:methods; D016208:Databases, Factual; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D054852:Small Molecule Libraries