Identification of Small Molecules that Disrupt Signaling between ABL and Its Positive Regulator RIN1
Fig 4
Elimination of off-target inhibitors.
(A) Two types of off-target inhibitors were predicted (red T-bars): compounds that quench GFP fluorescence, and biotin-like compounds that bind and sequester streptavidin. (B) Hit compounds were tested in triplicate dose-response curves with ABL-eGFP. Concentration response curve data from a representative GFP quencher (methyl 3,4,6-trihydroxy-5-oxo-5H-benzo[7]annulene-8-carboxylate) is shown. (C) Biotin mimics were identified by in silico screening for structural similarity to biotin. (D) Hit compounds were re-tested in the TR-FRET assay in triplicate 10-point dose-response curves to prioritize those with IC50<10 μM. Data from the representative compound CID 24512426 is shown.