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- W2015753469 abstract "JFCR39 COMPARE system is an anticancer drug‐activity database that we established by exploiting a panel of 39 human cancer cell lines. Molecular target of an agent can be predicted by comparing its cell growth inhibition profiles (fingerprint) with those of anticancer drugs using the COMPARE program. As accumulating evidences suggest close involvement of phosphatidylinositol 3‐kinase (PI3K) in various diseases, particularly in cancer, researchers in both industry and academics are in a race to develop PI3K inhibitors. Consequently, novel PI3K inhibitors such as ZSTK474, GDC‐0941, NVP‐BEZ235 and PI‐103 have been developed in recent years. Even though all these inhibitors were reported to inhibit class I PI3K but not dozens of protein kinases, whether they have different molecular targets remained unknown. To predict such molecular target specificity, we have examined the fingerprints of these novel PI3K inhibitors and classical PI3K inhibitor LY294002 across JFCR39 panel, and analyzed the results using the COMARE system. Interestingly, we found highly similar fingerprints for ZSTK474 and GDC‐0941 and cluster analysis distinguished them from the other three PI3K inhibitors, suggesting that ZSTK474 shared more in molecular targets with GDC‐0941 than with any other PI3K inhibitors. To test this prediction, we determined their effects on PI3K superfamily (including classes I, II, and III PI3Ks, PI4K and PI3K‐related kinases) by using several novel non‐radioactive biochemical assays. As a result, ZSTK474 and GDC‐0941 indicated highly similar inhibition profiles for PI3K superfamily, with class I PI3K inhibitory specificity much higher than the other three inhibitors, which supported the hypothesis derived from JFCR39 COMPARE result. In conclusion, JFCR39 system is able to provide valuable information regarding molecular target specificity, suggesting its utility in target identification with high resolution. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C67." @default.
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- W2015753469 date "2009-12-10" @default.
- W2015753469 modified "2023-09-25" @default.
- W2015753469 title "Abstract C67: JFCR39 COMPARE system can predict molecular targets of phophatidylinositol 3‐kinase inhibitors with high resolution" @default.
- W2015753469 doi "https://doi.org/10.1158/1535-7163.targ-09-c67" @default.
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