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Vismodegib binds USP28. 8 / 8
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"Finally, compound 14 was obtained by the deprotection of the Boc group.Based on the crystal structure of USP28 bound with Vismodegib, we initially explored the optimal fragment located in the solvent-[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Through the extensive optimization, we finally obtained several potent USP28 inhibitors, and further demonstrated the anticancer utility of the obtained compounds via the cell proliferation test and t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Therefore, the anti-cancer effects of three compounds could mainly be attributed to their inhibition on USP28 and might not involve the Hedgehog-Smoothened pathway.In summary, we obtained and solved t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"X-ray crystallography study demonstrated that Vismodegib was bound to USP28 protein via a novel allosteric pocket."
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"Multiple biophysical and biochemical techniques including NMR, ITC, thermal shift assay, HDX-MS and site directed mutagenesis analysis were then used to characterize the interaction between Vismodegib and USP28."
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"Furthermore, cellular assays were conducted to confirm that Vismodegib could interact with the evolutionarily related deubiquitinases USP28 and USP25 and down-regulate the levels of the two enzymes ' substrate proteins c-Myc, Notch1 and Tankyrase-1/2."
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"We discovered that the marketed anticancer drug Vismodegib ( 1 ) could directly bind to USP28, with an IC 50 value of 4.4 μM in the enzymatic inhibition assay [ 18 ]."
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"In current study, we firstly solved the X-ray structure of Vismodegib bound to USP28."
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