Table 3.

Interactions of Compounds 9–12 with Wild-type TTR and its V30M Variant

compound	Kd,2 (μM)	wild-type TTR		V30M TTR		binding modeb
		%FF 1:1a	%FF 2:1a	%FF 1:1a	%FF 2:1a
9	0.82 ± 0.01	30 ± 6	12 ± 2	62 ± 16	27 ± 10	NDc
10	0.47 ± 0.03	20 ± 3	3 ± 3	32 ± 9	8 ± 3	covalent
11	0.79 ± 0.03	26 ± 4	10 ± 3	54 ± 16	16 ± 5	forward/covalent
12 (tafamidis)	0.37 ± 0.01	22 ± 5	0 ± 6	5 ± 13	8 ± 7	forwardd

^a%FF, percent fibril formation.

^b”forward”: upper phenyl ring depicted in Chart 3 lies in the outer pocket of the T₄-binding site, according to X-ray diffraction analysis (Figure 2);¹⁸ “covalent”: formation of a boronate ester with Ser117.

^cND, not determined.

^dRef. ²¹.