Table 1.
Ongoing clinical trials or candidate targets of pharmacotherapies for the treatment of ALD or NAFLD
| Pathology | Target | Agent | Stage | Reference |
|---|---|---|---|---|
| ALD | Hepatic regeneration | IL-22 (F-652) | Phase 1 | [100] |
| IgG antibody to LPS | Bovine colostrum (IMM-124E) | Phase 2 | [101] | |
| Probiotic, restores gut microbiome | Lactobacillus rhamnosus GG | Phase 2 | [102] | |
| Antagonist to IL-1 receptor | Anakinra | Phase 2 | [103] | |
| FXR agonism | Obeticholic acid (INT-747) | Phase 2 | [104] | |
| Antibiotic amoxicillin plus clavulanic acid | Augmentin | Phase 3 | [105] | |
| Antioxidant and promotes abstinence | Metadoxine | Phase 4 | [106] | |
| Increase neutrophils, hepatic regeneration | G-CSF (filgrastim) | Phase 4 | [107] | |
| Glutamate | - | Target discovery stage | [108] | |
| HMGB1 | - | Target discovery stage | [109] | |
| ALDH2 | - | Target discovery stage | [110] | |
| Toll-like receptor 3 | - | Target discovery stage | [111] | |
| C3aR, C5aR1 | - | Target discovery stage | [112] | |
| Fructose, cytochrome P450-2E1 | - | Target discovery stage | [113] | |
| HIF-1α | - | Target discovery stage | [114] | |
| Lactobacillus GG | - | Target discovery stage | [115] | |
| Bile acid，FXR，FGF15 | - | Target discovery stage | [116] | |
| FGF19 | - | Target discovery stage | [117] | |
| FoxO1, miR-148a, TXNIP | - | Target discovery stage | [91] | |
| REG3 lectins | - | Target discovery stage | [118] | |
| NAFLD | Thyroid hormone receptor beta agonist | VK2809 | Phase 2 | [119] |
| PanPPAR agonist | Lanafibranor | Phase 2 | [120] | |
| FXR agonist and SGLT1/2 inhibitor | Tropifexor and licoglifozin | Phase 2 | [121] | |
| Engineered version of human hormone FGF19 | Aldafermin | Phase 2 | [122] | |
| FXR agonist | EDP-305 | Phase 2 | [123] | |
| ASBT inhibitor | Volixibat | Phase 2 | [124] | |
| Recombinant FGF21 | BMS-986036 | Phase 2 | [125] | |
| Pan-caspase inhibitor | Emricasan | Phase 2 | [126] | |
| Galectin 3 inhibitor | GR-MD-02 | Phase 2 | [127] | |
| CCR2/CCR5 receptor inhibitor | Cenicriviroc (AURORA) | Phase 3 | [128] | |
| SCD1 modulator | Aramchol | Phase 3 | [129] | |
| Thyroid hormone receptor beta agonist | Resmetirom | Phase 3 | [130] | |
| PPARα/δ ligand | Elafibranor (RESOLVE-IT) | Phase 3 | [131] | |
| FXR ligand | Obeticholic acid (REGENERATE) | Phase 3 | [132] | |
| FXR agonist | Obeticholic acid (REVERSE) | Phase 3 | [132] | |
| ASK1 inhibitor | Selonsertib | Phase 3 | [133] | |
| SGLT2 inhibitor | Gliflozin | Pilot | [134] | |
| LXRα, let-7a, miR-34a, ATG4B, Rab-8B | – | Target discovery stage | [50] | |
| STAT-1, STAT-3 | – | Target discovery stage | [135] | |
| Fructokinase | – | Target discovery stage | [136] | |
| Gα13, ITIH1 | – | Target discovery stage | [137] | |
| TAZ | – | Target discovery stage | [138] | |
| TNFAIP3 | – | Target discovery stage | [139] | |
| Glutaminase 1 | – | Target discovery stage | [140] | |
| USP22, Gα12, SIRT1 | – | Target discovery stage | [26] | |
| OTULIN | – | Target discovery stage | [141] |
ALD, alcoholic liver disease; NAFLD, non-alcoholic fatty liver disease; IL, interleukin; IgG, immunoglobulin G; LPS, lipopolysaccharide; FXR, farnesoid X receptor; G-CSF, granulocyte-colony stimulating factor; HMGB1, high mobility group box-1; ALDH2, aldehyde dehydrogenase 2; HIF, hypoxia-inducible factor; FGF, fibroblast growth factor; miR, microRNA; TXNIP, thioredoxin interacting protein; REG3, regenerating islet-derived protein 3; PanPPAR, pan-peroxisome proliferator-activated receptor; SGLT, sodium-glucose co-transporter; ASBT, apical sodium-dependent bile acid transporter; CCR, C-C chemokine receptor; SCD, stearoyl-CoA desaturase; PPAR, peroxisome proliferator-activated receptor; ASK1, apoptosis signal-regulating kinase 1; LXRα, liver X receptor α; ATG4B, autophagy related 4B cysteine peptidase; STAT, signal transducer and activator of transcription; Gα13, G protein subunit alpha 13; ITIH, inter-alpha-trypsin inhibitor heavy chain H1; TAZ, tafazzin; TNFAIP3, tumor necrosis factor alpha induced protein 3; USP, ubiquitin specific peptidase 22; SIRT, sirtuin 1; OTULIN, OTU domain-containing deubiquitinase with linear linkage specificity.