Table 1.
Drug | HDT Class | Host Target | Applications | Preclinical data in TB | Ref. |
---|---|---|---|---|---|
Doxycycline | MMP Inhibitors | Multiple MMPs | Bacterial infections | Improved TB containment in cells, guinea pigs; Phase II trial ongoing (NCT02774993) | (11) |
Marimastat | MMP Inhibitors | Multiple (MMP-1, -2, -7, -9, -14) | Cancer (discontinued) | Improved TB containment in mice | (12, 13) |
Andecaliximab | MMP Inhibitors | MMP-9 | Cancer, auto-inflammatory disorders (in development) | Reduced relapse rates in mice | (14, 15) |
Cipemastat | MMP Inhibitors | MMP-1, -8, -13 | Rheumatoid arthritis (discontinued) | Increased lung damage and death in mice; no effect in rabbits | (16, 17) |
Etanercept | TNF antagonists | TNFα | Arthritis (various forms), ankylosing spondylitis | Accelerated bacterial clearance, reduced relapse rates in mice; may improve outcome in TB-HIV patients (Phase I) or severely ill TB patients; risk of impaired bacterial containment without adequate anti-TB therapy | (15, 18–22) |
Dexamethasone/Prednisolone | Corticosteroids | Broad-spectrum anti-inflammatory effects via modulation of glucocorticoid/mineralocorticoid receptor signaling | Inflammatory and immune-mediated disorders (numerous) | Modest improvements in lung function; recommended for TB meningitis (survival benefit) but not for pulmonary TB | (23–31) |
Talazoparib | PARP inhibitors | PARP1/2; PARP3, PARP4, TNKS1, TNKS2 | Cancer | May reduce inflammation and TB lung damage in mice | (32–36) |
Olaparib | PARP inhibitors | PARP1/2; PARP3, PARP4, PARP16, TNKS1, TNKS2 | Cancer | N/A | (33, 34, 36) |
Rucaparib | PARP inhibitors | PARP1/2, PARP3, PARP10, TNKS1, TNKS2 | Cancer | N/A | (33, 34, 36) |
Niraparib | PARP inhibitors | PARP1/2, PARP3, PARP4, PARP12 | Cancer | N/A | (33, 34, 36) |
Metformin | MDSCs | HIF1α, CD39, CD73, AMPK-DACHi-CXCL1 | Diabetes | Reduced severity and mortality in diabetic patients | (37, 38) |
Tasquinamod | MDSCs | S100A9 | Cancer | Decreased lung and spleen bacillary burden in mice | (39) |
ATRA | MDSCs | Upregulates glutathione synthase | Cancer | Decreased lung bacillary burden and pathology in mice and rats | (40–42) |
DABIL-4 | MDSCs | IL-4R | Preclinical model of breast cancer | Decreased lung bacillary burden in mice | (43) |
Sildenafil | MDSCs | PDE-5i | Erectile dysfunction and pulmonary hypertension | Reduced lung bacillary burden, pathology and severity in mice | (44) |
Roflumilast and CC-11052 | MDSCs | PDE-4i | COPD | Improved lung function in mice | (45, 46) |
Denileukin Diftitox (Ontak®) | Tregs | IL-2R | Refractory cutaneous T-cell lymphoma | Reduced lung bacillary burden in mice | (47) |
Checkpoint blockade therapy | Tregs | CTLA4, PD1 | Cancer | Mtb-infected macaques overexpress CTLA-4 | (48) |
Curcumin | M2 macrophages | IL-10 | Preclinical models of cancer | Modest efficacy in mice | (49) |
Anti-IL-10 antibody | Tregs | IL-10 | Preclinical model of cancer | Reduced lung bacillary burden in mice | (50) |
MMP, matrix metalloproteinases; TNKS, tankyrase; PDE, phosphodiesterase.