TABLE 1.
Test compounds covering a range of metabolic areasa
| Compound | Target | Radioactive assay result | MIC for ARC523 wild type (μg/ml) | MIC for ARC524 TolC− (μg/ml) |
|---|---|---|---|---|
| 1-[3-Fluoro-4-(5-methyl-2,4-dioxo-pyrimidin-1-yl)phenyl]-3-[2-(trifluoromethyl)phenyl] urea (AZ1) | Thymidylate kinaseb | DNA | >64 | 0.0625–0.125 |
| 2-(Cyclobutylmethoxy)-5′-deoxyadenosine | DNA ligasec | Mixed | >64 | 2–8 |
| Triclosan | Fatty acid metabolismd | Fatty acid | 0.25 | 0.0039 |
| Fosmidomycin | Deoxyxylulose 5-phosphate reductoisomerasee | No inhibition | 2 | 2 |
| CHIR-090 | UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC)f | Mixed | 0.125 | 0.0078 |
| CCCP | Oxidative phosphorylation | Mixed | 32 | 0.5–1 |
| 5-Chloro-2-(methylsulfonyl)-N-(1,3-thiazol-2-yl)-4-pyrimidinecarboxamide (AZ7) | Unknown | Mixed | >64 | 16 |
| Ceftazidime | Penicillin binding proteinsg | Cell wall | 0.25–0.5 | 0.25–0.5 |
a
MICs of AZ compounds in wild-type E. coli ARC523 and the TolC mutant, strain ARC524. n ≥ 3. Where different values were found among the replicates, a range is shown.
b
From reference 32.
c
From reference 45 and M. Cavero-Tomas, M. Gowravaram, H. Huynh, H. Ni, and S. Stokes, PCT international patent application WO 2006040558 A1 20060420 (2006).
d
From reference 46.
e
From reference 47.
f
From reference 35.
g
From reference 2.