Table 2.

Comparison of selection profiles, in vitro assay potencies, and SPR-binding constants for InhA inhibitors

Compound	Series	Profile class	InhA NAD+ assay IC50, µM	InhA NADH assay IC50, µM	InhA NAD+ SPR Kd, µM	InhA NADH SPR Kd, µM	InhA Apo SPR Kd, µM
11	11	1	0.389 ± 0.007	0.168 (n = 1)	NT	NT	NT
10a	10	2	0.038 ± 0.006	0.198 ± 0.009	0.26 ± 0.12	5 ± 1.20	12.4 ± 1.41
12	12	2	0.682 ± 0.207	6.838 ± 0.175	NT	NT	NT
2a*	1–3	3	0.060 ± 0.004	0.057 ± 0.006	46.7 ± 11.6	0.094 ± 0.06	>100
13	13	3	0.791 ± 0.008	0.609 ± 0.114	NT	NT	NT
8a*	8 and 9	3	NT	0.130 ± 0.006	49 ± 2.90	0.055 ± 0.03	>100
6a*	6 and 7	3	NT	5.917 ± 1.22	>100	36.8 ± 3.25	>100
4a*	4 and 5	3	NT	0.297 ± 0.053	>100	0.25 ± 0.11	>100
1a*	1–3	3	NT	0.065 ± 0.008	13.4 ± 4.30	0.34 ± 0.22	>100
14	14	3	NT	5.568 ± 0.777	>100	6.3	>100

Profile classes: 1, enriched only in the presence of apo InhA; 2, enriched only in the presence of the InhA:NAD⁺ complex; 3, enriched only in the presence of the InhA:NADH complex but not in presence of small molecule. NT, not tested. Chemical structures for compounds 11–14 are given in Fig. S1.

^*WT InhA cocrystal structures reported herein.