Table 1.

Biochemical and cellular activity of InhA inhibitors described in the literature (Fig. 1) that show cellular activity in Mycobacterium tuberculosis

Compound	Reported affinity, nM	Cellular activity: MIC50, µM (H37Rv)	cLogP	LLE	Predominant InhA binding
1	0.79*	0.158	−0.7†	9.8	Apo
2	0.02‡	10.000	7.0	3.7	NAD+
3	6309.57§	0.398	3.1	2.1	Apo
4	3.16§	0.199	2.3	6.2	NADH
5	3.98¶	0.501#	1.4	7.0	ND
6	630.96¶	0.079	5.3	0.9	NADH‖

cLogP, the calculated logarithms of water-octanol partition coefficients; LLE, log₁₀ of reported affinity − cLogP; ND, not determined.

^*K_i measurement.

^†cLogP calculated for prodrug isoniazid rather than active drug INH-NAD adduct.

^‡K₁ measurement.

^§K_d measurement.

^¶IC₅₀.

^#MIC₉₀.

^‖A close analog, NITD-529, showed binding only to NADH form of InhA.