Subsequent publications refined the pharmacophore using members of the Mycobacterium avium complex (MAC), which established that SRI-8686 had the highest IC50 ratio for MAC DHFR vs human DHFR (0.84 nM vs 2,300 nM, a 2,700-fold selectivity). SRI-8117 showed similar selectivity (1.1 nM vs 1,000 nM, 900-fold selectivity) [324]. Other MTb DHFR inhibitors are in early stages of development [325]. Although the MIC assays suggest that this series may be worth developing, the on-target effect of these compounds in MTb still needs to be verified.

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