TABLE 1.
Characterization of MmpL3 inhibitors
| Compound | Clade | EC50 (μM) |
Δψ disruption | CC50 (μM) | Solubility (μM) | Microsome stability (% remaining after 30 min) | |||
|---|---|---|---|---|---|---|---|---|---|
| WT | mmpL3 mutant pool | Differentiala | Mϕ | ||||||
| HC2032 | B | 2.2 | >80 | >36 | 0.8 | Yes | >100 | 18 | 102 |
| HC2060 | B | 16.9 | >80 | >5 | 4.1 | No | >100 | >300 | 44 |
| HC2091 | B | 6.2 | >80 | >13 | 2.2 | No | >100 | >300 | 45 |
| HC2099 | B | 1.7 | 38.9 | 23 | <0.3 | Yes | >100 | 178 | 71 |
| HC2134 | A | 1.4 | >80 | >57 | 7.3 | Yes | >100 | 116 | NDb |
| HC2138 | A | 4.0 | >80 | >20 | <0.3 | Yes | >100 | 66 | 122 |
| HC2149 | A | 6.6 | >80 | >12 | 3.6 | Yes | >100 | 131 | 138 |
| HC2169 | A | 1.8 | >80 | >44 | <0.3 | No | >100 | 17 | 168 |
| HC2178 | B | 3.8 | >80 | >24 | 2.0 | Yes | >100 | >200 | 4 |
| HC2183 | B | 3.2 | 59.9 | 19 | 3.0 | No | >100 | >200 | 25 |
| HC2184 | B | 7.6 | >80 | >11 | 0.7 | Yes | >100 | >300 | 30 |
| C215 | B | 11.2 | 57.5 | 5 | 4.0 | Yes | 14.3 | 87 | 62 |
| SQ109 | B | 2.4 | 6.9 | 2 | <0.3 | Yes | ND | ND | ND |
a
Differential EC50 is the fold difference between the EC50s of the WT and the mmpL3 mutant pool.
b
ND, not determined.