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. Author manuscript; available in PMC: 2020 Nov 1.
Published in final edited form as: Alzheimers Dement. 2019 Oct 22;15(11):1489–1502. doi: 10.1016/j.jalz.2019.06.4954

Fig. 3: Identification of MK-886 as a small molecule that directly perturbs conformational ensemble of tau oligomers.

Fig. 3:

(A) Representative pilot screening with NCC library containing 727 compounds. A FRET efficiency cutoff threshold was applied at a change in FRET efficiency of 5SD (black lines). Five reproducible hits decreased FRET by more than 5SD below the mean of all cells (red) and MK-886 induced the largest FRET change (arrow). Surface plasmon resonance (SPR) binding curve for MK-886 to purified recombinant full-length 2N4R (B) wild-type (WT) and (C) P301L tau proteins. (D) FRET analysis of the dose response of MK-886 in both WT and P301L tau inter-molecular biosensors indicates EC50 values of 1.40 and 1.84 μM respectively. Data are means ± SD of three independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001 by two-tailed unpaired t test.