TABLE 4.

Selected single-enzyme inhibitors discovered by empirical or phenotypic screeninga

Target category and targetInhibitor(s)b discovered by:
Empiric screeningPhenotypic screening
DNA replication and substrates
    GyrA Nalidixic acid (137)Pyrazole derivatives (360)
    GyrB (276)Novobiocin, coumermycin, clorobiocin, cyclothialidine
    NdkDesdanine (318, 330)
Cell wall synthesis and cell division
    MurAFosfomycin (155, 181)
    IspCFosmidomycin (202, 279)
    WalK/WalRAranorosinol B (383)
    SAV1754 (flippase? MurJ?) Compound D (263) DMPI, CDFI (166)
    FtsZSanguinarine (37), curcumin (307)
Transcription, translation, and chaperones
    RNA polymerases (72)Rifamycins, streptolydigin, lipiarmycin, sorangicin
    tRNA synthetases (RS) (73)
        IleRSMupirocin
        TrpRSIndolmycin
        PheRSOchratoxin
        ThrRSBorrelidin
        LeuRSGranaticin
        ProRSCispenticin
    Ef-G (73)Fusidic acid
    Ef-Tu (291)Kirromycin, enacyloxin, pulvomycinGE2270 (327)
    PdfActinonin (68)
Lipid and membrane synthesis
    FabFPlatensimycin (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.