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. Author manuscript; available in PMC: 2018 Aug 1.
Published in final edited form as: Bioorg Med Chem Lett. 2017 May 26;27(15):3441–3449. doi: 10.1016/j.bmcl.2017.05.080

Figure 7.

Figure 7

Examination of the correlations between corrected in silico docking scores of candidate kinetic stabilizers and their in vitro % inhibition of TTR aggregation (A); ex vivo plasma TTR binding stoichiometry (B); Experimental Efficacy Scores (C); Relative Thyroid Hormone receptor binding (D); and Thyroid Hormone Receptor Experimental Efficacy Scores (E). Please refer to Table S1 in the Supporting Information for a complete tabulation of all values. In panels A, B, C, and E, solid black data points represent the percentage of compounds within the 0.5 docking score bins that are above the respective thresholds (90% for inhibition of TTR aggregation for panel A; 1 molecule bound per TTR tetramer for panel B; and 0.667 for C and E, representing 100% inhibition of TTR aggregation and 1 molecule bound per tetramer). In panel D, solid black data points represent the percentage of compounds within the 0.5 docking score bins that are below the 0.2 threshold for undesirable thyroid hormone receptor binding. Areas shaded grey represent the docking score regions where significant enrichment of molecules above the respective cutoffs occur (or below with respect to thyroid hormone receptor binding). In panel E, the greatest proportion of highly desirable, potent, and selective TTR aggregation inhibitors are predicted within the −7.5 to −9.0 docking score region.