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- W2023893511 abstract "1 Microtubule binding drugs are of special interest as they have important roles in the modulation of cellular functions and many of them act as anticancer agents. 4-Amino-5-benzoyl-2-(4-methoxyphenylamino)thiazole (DAT1) was identified as one of the active compounds from a series of diaminoketothiazoles in a cell-based screening assay to discover cytotoxic compounds. 2 DAT1 shows cytotoxicity with GI50 values ranging from 0.05 to 1 μM in different malignant cell lines with an average value of 0.35 μM. It blocks mitosis in the prometaphase and metaphase stages. In HeLa cells, DAT1 blocks the spindle function by disturbing spindle microtubule and chromosome organization. 3 The drug also inhibits assembly of brain microtubules and binds tubulin specifically at a single site with induction of fluorescence. The dissociation constant of DAT1 binding to tubulin was determined as 2.9±1 μM at 24°C. The binding site of DAT1 on tubulin overlaps with that of the conventional colchicine-binding site. 4 DAT1 can thus be considered as a lead compound of a new class of small molecules and this study can be used as a step to develop potent antimitotic agents for the control of cytoskeletal functions and cell proliferation. It would also be an interesting probe for the structure–function studies of tubulin–microtubule system. British Journal of Pharmacology (2005) 145, 1076–1083. doi:10.1038/sj.bjp.0706276; published online 13 June 2005" @default.
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- W2023893511 date "2005-08-01" @default.
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- W2023893511 title "4-Amino-5-benzoyl-2-(4-methoxyphenylamino)thiazole (DAT1): a cytotoxic agent towards cancer cells and a probe for tubulin-microtubule system" @default.
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- W2023893511 doi "https://doi.org/10.1038/sj.bjp.0706276" @default.
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