Table 2.
Anti-TB drug candidates in different phases of the drug development process: 2010–2020.
| Chemical Class | Novel Drug | MW g/mol | LogP (ChemDraw) |
Clinical Phase | Cellular Target | Tmax h |
AUC mg.h/L a ng.h/mL b µg.h/mLc | T1/2 h |
CYP450 Inhibition |
|---|---|---|---|---|---|---|---|---|---|
| Fluoroquinolones | Moxifloxacin | 401.43 | 1.60 | III | DNA gyrase and Topoisomerases |
1.5 | 26.9a | 11.5–15.6 | – |
| Gatifloxacin | 375.39 | 1.2 | III | DNA gyrase and Topoisomerases |
1–2 | 51.3 a | 7–14 | – | |
| DC-195a | 421.44 | 1.24 | Pre-clinical | DNA Replication | – | 15.8 a | 1.51–1.93 | Un-confirmed | |
| Diarylquinolones | Bedaquiline | 555.50 | 7.52 | IIb/III | ATP Synthase | 4–6 | 65 a | 21.7–24 | Moderate–high risk |
| TBAJ-876 | 657.56 | 6.08 | Pre-clinical | ATP Synthase | – | 4.61 c | – | – | |
| TBAJ-587 | 614.5 | 6.4 | Pre-clinical | ATP Synthase | – | 1.72 c | – | – | |
| Oxazolidinone | Linezolid | 337.35 | 0.58 | Iib | Protein synthesis | 1–2 | 210 a | 6–7.9 | – |
| Sutezolid | 353.41 | 1.3 | Iia | Protein synthesis | 0.5 | 31945 b | 2.8–4 | Substrate | |
| AZD5847 | 465.40 | 0.7 | Iia | Protein synthesis | 2–4 | 93.19 c | 7–11 | – | |
| Nitroimidazoles | Delamanid | 534.5 | — | III | Cell Wall Acids Synthesis |
4–5 | 2.9 a | 30–38 | Liver CYP3A |
| Pretomanid | 359.26 | — | III | Cell Wall, Lipids, and Protein synthesis | 4–5 | 53 c | 10–30 | Insignificant | |
| TBA 354 | 436.30 | — | II | Cell Wall, Lipids, and Protein synthesis | 2–6 | 22.7–242 c | 8–12 | Weak CYP3A4 | |
| Ethylenediamines | SQ109 | 330.50 | 4.44 | Iib/III | Cell Wall Acids Synthesis | 1 | 183.7–268.5 b | 19.6 | CYP2D6, CYP2C19 & weak CYP3A4 |
| Benzothiazinones | BTZ043 | 431.40 | — | Pre-clinical | DprE1 | 0.25 | 899 b | 1.22 | Low |
| PBTZ169 | 456.48 | 4.42 | II | DprE1 | 1.5–2.5 | 5478 b | 2.87 | – | |
| Carbostyrils | OPC-167832 | 456.85 | 2.82 | I | DprE1 | 0.5–1 | Dose dependent | 1.3–2.1 | – |
| TBA-7371 | 355.40 | 1.31 | I | DprE1 | – | 166–240 c | – | – | |
| Imidazopyridine amides | Q203 | 557.01 | 7.64 | Pre-clinical | QcrB | 2 | 44100 b | 23.4 | – |
| TB47 | 538.57 | 6.61 | QcrB | 3.2 | 33144 c | 35.6 | Insignificant | ||
| ND-11543 | 532.56 | 5.84 | QcrB | 2 | 11704 b | 24 | Substrate | ||
| Caprazamycins | CPZEN-45 | 688.70 | −2.59 | Pre-clinical | Cell wall Peptidoglycan biosynthesis (WecA) |
– | – | – | – |
| Oxaboroles | GSK070 (3036656) | 257.48 | — | II | LeuRS | – | – | – | – |
| Riminophenazines | TBI-166 | 589.60 | 5.08 | Pre-clinical | DNA Synthesis (QcrB) | 2.7 | 2658.2 b | 20.4 | – |
| Hydrazides | LL3858 | 519.57 | 5.31 | I | Undefined | – | – | – | – |
| Pyrroles | BM212 | 414.40 | 5.30 | Lead Optimisation | MmpL3 Protein | – | – | – | – |
| Oxoborates | GSK-693 | 419.54 | 5.69 | Lead Optimisation | InhA | – | – | – | CYP3A4 |
| NITD-916 | 311.42 | 2.56 | Lead Optimisation | InhA | – | – | – | – | |
| Β-lactams | Faropenem | 285.31 | −1.62 | II | L,D-traspeptidase | 2 | 16.2 a | 1.2 | – |
| Ertapenem | 475.52 | −1.72 | II | L,D-traspeptidase | – | 544.9 a | 4 | – |
Units for AUC: a = mg.h/L, b = ng.h/mL, c = µg.h/mL.