Table 3.

Results of FP competitive binding and compound cytotoxicity for a set of carboxamides based on the most potent fragment (31). Reported values are the average of triplicate measurements ± SEM. NT = not tested.

Compound	R	FP EC50 (μM)	FP Ki (μM)	BEIa	LEIb	CC50 (μM)c
33		3.66 ± 0.08	0.99 ± 0.03	20.9	0.40	>60
34		88.12 ± 0.05	28.57 ± 0.01	15.0	0.30	NT
35		216.7 ± 1.5	70.5 ± 0.7	13.0	0.27	NT
36		>250				NT
37		11.48 ± 0.01	3.556 ± 0.004	17.3	0.33	NT
38		5.41 ± 0.06	1.65 ± 0.02	17.9	0.33	>60
39		22.6 ± 0.2	7.1 ± 0.1	15.3	0.28	>60
40		3.7 ± 0.5	1.2 ± 0.2	17.3	0.33	>60
41		35.3 ± 0.8	11.2 ± 0.3	14.0	0.26	>60
42		3.5 ± 0.3	0.72 ± 0.05	18.2	0.34	>60
43		>250				>60
44		7.67 ± 0.03	2.28 ± 0.01	16.7	0.31	>60
45		1.5 ± 0.2	0.29 ± 0.06	19.4	0.36	>60
46		5.52 ± 0.09	1.61 ± 0.03	16.5	0.31	>60
47		4.851 ± 0.007	1.392 ± 0.002	17.0	0.32	7.1
48		3.5 ± 0.6	1.0 ± 0.3	17.0	0.32	>60
49		24.3 ± 0.4	7.6 ± 0.3	14.1	0.26	10.2

^aBEI = binding efficiency index (pK_i/MW), where MW is molecular weight in kDa (55).

^bLE = ligand efficiency (ΔG/N), where ΔG = -RTlnK_i and N is the number of non-hydrogen atoms (56).

^cMeasured in MDCK cells as 2-fold dilutions from 60 μM.