TABLE 1.
Biological targets and inhibitors targeting Mtb.
| Mechanism of action | Target | Typical compound | Drug stage for TB | |
|---|---|---|---|---|
| Cell wall synthesis and sssembly | MA a biosynthesis | Enoyl‐acyl carrier protein reductase (InhA) | Isoniazid 38 | Approved |
| Ethionamide 39 | Approved | |||
| β‐Ketoacyl synthase (KasA) | Thiolactomycin 66 , 67 , 68 , 69 | Biological test | ||
| Fatty acid degradation protein D32 (FadD32) | Quinoline‐2‐carboxamide 78 | Biological test | ||
| Polyketide synthase 13 (Pks13) | TAM16 79 | Biological test | ||
| Mycolic acid methyltransferase 4 (MmaA4) | SADAE 88 | Biological test | ||
| Cyclopropane mycolic acid synthase (CMAS) | / | In silico docking | ||
| AG biosynthesis | N‐acetylglucosamine‐1‐phosphate transferase (WecA) | CPZEN‐45 97 | Preclinical | |
| LAM biosynthesis | Arabinosyl transferase C (EmbC) | Amikacin 106 | Approved | |
| Decaprenylphosphoryl‐β‐D‐ribose‐2′‐epimerase (DprE1) | PBTZ‐169 110 | Phase I | ||
| OPC‐167832 111 | Phase II | |||
| TBA‐7371 112 | Phase II | |||
| BTZ‐043 113 | Phase II | |||
| PG biosynthesis | Alanine racemase (Alr) | Cycloserine 130 , 131 | Approved | |
| D‐alanyl‐D‐alanine ligase (Ddl) | ||||
| L,D‐transpeptidase type 2 (LdtMt2) | Meropenem 138 | Approved | ||
| Phospho‐N‐acetylmuramoyl‐pentapeptide transferase (MurX) | SQ641 148 , 149 | Preclinical | ||
| MA transporter | Mamalian membrane protein large 3 (MmpL3) | SQ109 155 | Phase II | |
| Lipid metabolism | Aspartate decarboxylase (PanD) | Pyrazinamide 171 , 172 | Approved | |
| Protein synthesis and breakdown | Ribosome | TBI‐223 191 | Phase I | |
| Leucyl‐tRNA synthase (LeuRS) | GSK656 194 | Phase II | ||
| Caseinolytic protease P (ClpP) | EZ120 200 | Preclinical | ||
| Proteasome | Phenylimidazole 210 | Preclinical | ||
| Proteasome accessory factor A (PafA) | ST1926 213 | Biological test | ||
| Amino acid synthesis and metabolism | Ser/Thr protein kinases (protein kinase G, PknG) | AX20017 220 | Biological test | |
| NU‐6027 224 | Biological test | |||
| Shikimate pathway (3‐dehydroquinate synthase, DHQS) | IMB‐T130 228 | Biological test | ||
| Tryptophan synthase (TrpAB) | BRD4592 233 | Preclinical | ||
| Nucleotide synthesis | Type I topoisomerase (topoI) | m‐AMSA 241 | Biological test | |
| Type II topoisomerase (DNA gyrase) | Levofloxacin 244 | Phase II | ||
| SPR720 246 | Phase II | |||
| RNA polymerase (RNAP) | Rifampicin 252 | Approved | ||
| transcriptional repressor of ethA (EthR) | BVL‐GSK098 257 , 258 | Phase 1 | ||
| Energy metabolism | Type II NADH dehydrogenase (NDH‐2) | Clofazimine 263 | Phase III | |
| TBI‐166 264 | Phase I | |||
| β Subunit of cytochrome bc 1 complex (QcrB) | Telacebec 268 | Phase II | ||
| ATP synthase | Bedaquiline 276 | Phase III | ||
| TBAJ‐876 280 | Phase I | |||
| TBAJ‐587 280 | Phase I | |||
| WX‐081 281 | Phase II | |||
| Virulence | Two‐component system | PhoPR | Ethoxzolamide 294 | Biological test |
| Artemisinin 299 | Biological test | |||
| DosRST | HC102A 299 | Biological test | ||
| HC103A 299 | Biological test | |||
| ESX‐1 secretion system | ESAT‐6 secretion system‐1 (ESX‐1) | BBH7 306 | Biological test | |
| BTP15 306 | Biological test | |||
| Folic acid and mycobactin biosynthesis | Dihydrofolate reductase (DHFR) | P‐aminosalicylic acid 308 | Approved | |
| AF‐353 311 | Biological test | |||
| Metal uptake | Iron‐dependent regulator (IdeR) | / | In silico docking | |
| Cholesterol metabolism | Adenylyl cyclase (AC) | GSK2556286 316 | Phase I | |
a
MA, mycolic acid; AG, arabinogalactan; LAM, lipoarabinomannan; PG, peptidoglycan.