TABLE 4.
Selected single-enzyme inhibitors discovered by empirical or phenotypic screeninga
| Target category and target | Inhibitor(s)b discovered by: |
|
|---|---|---|
| Empiric screening | Phenotypic screening | |
| DNA replication and substrates | ||
| GyrA | Nalidixic acid (137) | Pyrazole derivatives (360) |
| GyrB (276) | Novobiocin, coumermycin, clorobiocin, cyclothialidine | |
| Ndk | Desdanine (318, 330) | |
| Cell wall synthesis and cell division | ||
| MurA | Fosfomycin (155, 181) | |
| IspC | Fosmidomycin (202, 279) | |
| WalK/WalR | Aranorosinol B (383) | |
| SAV1754 (flippase? MurJ?) | Compound D (263) | DMPI, CDFI (166) |
| FtsZ | Sanguinarine (37), curcumin (307) | |
| Transcription, translation, and chaperones | ||
| RNA polymerases (72) | Rifamycins, streptolydigin, lipiarmycin, sorangicin | |
| tRNA synthetases (RS) (73) | ||
| IleRS | Mupirocin | |
| TrpRS | Indolmycin | |
| PheRS | Ochratoxin | |
| ThrRS | Borrelidin | |
| LeuRS | Granaticin | |
| ProRS | Cispenticin | |
| Ef-G (73) | Fusidic acid | |
| Ef-Tu (291) | Kirromycin, enacyloxin, pulvomycin | GE2270 (327) |
| Actinonin (68) | ||
| Lipid and membrane synthesis | ||
| FabF | Platensimycin (381) | |
| LpxC | L573,655; L-161,240 (283) | |
| AccC | Pyridopyrimidine (255) | |
a
References after specific inhibitors are to the discovery and/or mechanism of action of the inhibitor; references in the first column are to reviews covering the compounds hitting that target.
b
Synthetic compounds are shown in italics.