TY - JOUR
T1 - Morphobase, an encyclopedic cell morphology database, and its use for drug target identification
AU - Futamura, Yushi
AU - Kawatani, Makoto
AU - Kazami, Sayaka
AU - Tanaka, Kenichi
AU - Muroi, Makoto
AU - Shimizu, Takeshi
AU - Tomita, Koji
AU - Watanabe, Nobumoto
AU - Osada, Hiroyuki
N1 - Funding Information:
We thank Y. Uehara (Iwate Medical University) for kindly providing src ts -NRK cells, F. Koizumi (National Cancer Center Research Institute) for providing H69, H69/VDS, and H69/Txl cells, J. Kobayashi (Hokkaido University) for providing iejimalide A, and H. Nakamura (Gakushuin University) for providing GN26361 and mizoribine. The SCADS inhibitor kits were a kind gift of the Screening Committee of Anticancer Drugs supported by a Grant-in-Aid for Scientific Research on Innovative Areas, Scientific Support Programs for Cancer Research from MEXT. We also thank H. Aono, Y. Fukushima, K. Noda, and H. Kondo for technical assistance, K. Wierzba and T. Motoyama for critical review of the manuscript, and members of RIKEN NPDepo for the chemical libraries. This work was supported in part by a Special Postdoctoral Research Program of RIKEN, Grant-in-Aid for Scientific Research (KAKENHI), Health and Labour Sciences Research Grant, and the Program for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry.
PY - 2012/12/21
Y1 - 2012/12/21
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chembiol.2012.10.014
DO - 10.1016/j.chembiol.2012.10.014
M3 - Article
C2 - 23261605
AN - SCOPUS:84871589905
SN - 2451-9448
VL - 19
SP - 1620
EP - 1630
JO - Cell Chemical Biology
JF - Cell Chemical Biology
IS - 12
ER -
