TABLE 3.

Inhibitors discovered through enzyme screening or designd

TargetFunctionNonantibacterial enzyme inhibitor(s)Antibacterial inhibitor(s) (some with SAR)Inhibitor(s) with some genetic/phenotypic evidence (but insufficient for proof)Inhibitor(s) with probable additional targetWell-validated antibacterial inhibitor(s)
MurACell wallT6362R (107)Compound 1 (28)
Three compounds (33)
MurIGlu racemase d-Glu analogsb (88)Pyrazolopyrimidinedione (89)
Cell wallPyridodiazepine amines (129)
MurGCell wallRhodanines (163)
WalK/WalRCell wall regulationThiazolidinones,c benzamides,c pyrimidinonec (305)
UppSBactoprenol synthesisTetramicc and tetronicc acids (297)
FtsZCell divisionZantrins (236)
C-seco-taxanesb (164)3-Methoxybenzamide (MBO) (277)
Dichamanetin (372)PC190723b (81, 151)
Viridotoxin (379)Cmpd 2 (MBO derivative)b (150)
4-Aminofurazan (173)
FabI (FabL and -K)Fatty acid synthesisLuteolinc (396)Imidazoles (154)Thiopyridines (214)Aminopyridines (177, 258, 294)
Enoyl-reductasesAquastatins (203)AFN1252a (185), MUT37307a , b(106), CG400549 (290)
Curcuminc (396)
FabKFatty acid synthesisPhenylimidazole derivatives of 4-pyridoneb (193), AG205 (357)
Enoyl-reductases
CoaACoenzyme APantothenic acid derivativesb (74)
AccA, AccDAcetyl-CoA carboxylaseMoiramide B (120, 121)
Pyridopyrimidines (255)
Pyrrolidinediones (122)
LpxCLipid A deacetylaseUDP analogsc (25)BB-78485 (76)
Hydantoinsb (80)CHIR-090b (247)
LptD (Imp)LPS translocasePeptidomimetic (350)
RpoB and -CRNA polymeraseSB-2 (rhodanine) (10)CBR703 (15)
Ureidothiphenes (14)
Ef-TuTranslation elongationIndole-dipeptide (176)
LeuRSLeu tRNA synthetaseABX (benzoxaborole) (123)
MetRSMet tRNA synthetaseREP 8839 (139, 175)
PheRSPhe tRNA synthetaseThiazolylurea-sulfonamides (38)
Spirocyclic tetrahydrofurans (157)
PdfPeptidyl deformylaseActinonin (68), BB-3497a (75)
Ro 66-6976, Ro 66-0376 (66)
LBM-415a (209), N-alkyl urea hydroxamic acids (145)
MapMet aminopeptidasePyrazolediaminesc (109)Catechol thiazoles, catechol thiophenes (382)
PolCDNA polymerase IIICAnilinopyrazolopyrimidinonesb (4)Anilino-uracilsb (53, 221)
HB-EMAUb (59), EMAIPUb (199)
DnaGDNA primaseBenzopyrimido-furans,c pyridothieno-pyrimidinec
MenAMenaquinone synthaseHydrazine or tertiary or secondary amine-containing mimics of demethylmenaquinoneb (200)
ClpXPProteaseCyclic peptide IXP1 (70)
DnaKChaperoneTetradecanoyl-aminomethylbenzoyl- l-isoleucineb (213)
His kinasesSignal transducersThieno-pyridine (132)
  • a Compound has reached clinical trials.

  • b Compound or series based on substrates or optimized from previously known inhibitors.

  • c Compound or series discovered through in silico screening based on crystallographic data.

  • d Definitions of column headings are given in the text.