Therapeutic Strategy Details
| Strategy ID: | S05 |
| Strategy: | Anti-inflammatory |
| Other Terms: | inflammatory |
| Related Targets: | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor |
| Related Drugs: | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; |
| Mechanism: | The pathogenesis of NAFLD is multifactorial, but inflammation is considered the key element of disease progression. The liver harbors an abundance of resident immune cells, that in concert with recruited immune cells, orchestrate steatohepatitis. While inflammatory processes drive fibrosis and disease progression in NASH, fueling the ground for HCC development, immunity also exerts antitumor activities. Furthermore, immunotherapy is a promising new treatment of HCC, warranting a more detailed understanding of inflammatory mechanisms underlying the progression of NASH and transition to HCC. Novel methodologies such as single-cell sequencing, genetic fate mapping, and intravital microscopy have unraveled complex mechanisms behind immune-mediated liver injury. |
| Reference (PMIDs): | 8675165; 33578800 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T03 | Peroxisome proliferator-activated receptor alpha | PPARA | agonist | Nuclear hormone receptor | Q07869 | PPARA_HUMAN | Details |
| T04 | Peroxisome proliferator-activated receptor delta | PPARD | agonist | Nuclear hormone receptor | Q03181 | PPARD_HUMAN | Details |
| T24 | C-C chemokine receptor type 2 | CCR2 | antagonist | GPCR | P41597 | CCR2_HUMAN | Details |
| T25 | C-C chemokine receptor type 5 | CCR5 | antagonist | GPCR | P51681 | CCR5_HUMAN | Details |
| T40 | N-formyl peptide receptor 2 | FPR2 | inhibitor | Enzyme | P25090 | FPR2_HUMAN | Details |
| T41 | X-box-binding protein 1 | XBP1 | inhibitor | Protein | P17861 | XBP1_HUMAN | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D002 | Acetaminophen | Chemical drug | DB00316 | PTGES3 inhibitor; TRPV1 activator | Antipyretic drug; non-narcotic analgesic | Under clinical trials | Details |
| D008 | Alpha-tocopherol | Chemical drug | DB00163 | NR1I2; ALOX5; DGKA | -- | Under clinical trials | Details |
| D009 | ALS-L1023 | Chemical drug | -- | PPARA / Angiogenesis | Anti-inflammatory | Under clinical trials | Details |
| D011 | Anthocyanin | Chemical drug | -- | -- | Anti-inflammatory | Failed in clinical trials | Details |
| D018 | Aspirin | Chemical drug | DB00945 | AKR1C1 inhibitor; PCNA downregulator | Enhance lipid metabolism | Under clinical trials | Details |
| D019 | Astaxanthin | Chemical drug | DB06543 | -- | -- | Under clinical trials | Details |
| D025 | Azithromycin | Chemical drug | DB00207 | -- | -- | Under clinical trials | Details |
| D027 | Bayberry Juice | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D033 | Bezafibrate | Chemical drug | DB01393 | PPARA agonist; PPARD agonist; PPARG agonist; NR1I2 partial agonist | Improve insulin resistance; Anti-inflammatory | Under clinical trials | Details |
| D043 | Bismuth subcitrate | Chemical drug | DB09275 | -- | -- | Under clinical trials | Details |
| Candidate ID | Source ID | Source Type | Compound Type | Candidate Name | Inclusion Criteria | |
|---|---|---|---|---|---|---|
| R0002 | DB00003 | approved | biotech | Dornase alfa | Therapeutic strategy associated | Details |
| R0003 | DB00005 | approved; investigational | biotech | Etanercept | Therapeutic strategy associated | Details |
| R0009 | DB00026 | approved | biotech | Anakinra | Therapeutic strategy associated | Details |
| R0010 | DB00028 | approved; investigational | biotech | Human immunoglobulin G | Indication associated | Details |
| R0014 | DB00043 | approved; investigational | biotech | Omalizumab | Therapeutic strategy associated | Details |
| R0017 | DB00051 | approved; experimental | biotech | Adalimumab | Therapeutic strategy associated | Details |
| R0020 | DB00065 | approved | biotech | Infliximab | Therapeutic strategy associated | Details |
| R0022 | DB00073 | approved | biotech | Rituximab | Therapeutic strategy associated | Details |
| R0027 | DB00091 | approved; investigational; vet_approved | small molecule | Cyclosporine | Therapeutic strategy associated | Details |
| R0031 | DB00108 | approved; investigational | biotech | Natalizumab | Therapeutic strategy associated | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A00007 | 35256601 | Cell Death Discov | LncRNA MEG3 up-regulates SIRT6 by ubiquitinating EZH2 and alleviates nonalcoholic fatty liver disease. | Details |
| A00030 | 35250593 | Front Pharmacol | Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease. | Details |
| A00031 | 35250588 | Front Pharmacol | Platelets in Non-alcoholic Fatty Liver Disease. | Details |
| A00041 | 35247611 | Mol Metab | Serum Amyloid A1 Exacerbates Hepatic Steatosis via TLR4 Mediated NF-κB Signaling Pathway. | Details |
| A00049 | 35243280 | JHEP Rep | Cellular origins of regenerating liver and hepatocellular carcinoma. | Details |
| A00062 | 35235789 | Cell Rep | Distinct hepatic immunological patterns are associated with the progression or inhibition of hepatocellular carcinoma. | Details |
| A00082 | 35227772 | Life Sci | sSTEAP4 regulates cellular homeostasis and improves high-fat-diet-caused oxidative stress in hepatocytes. | Details |
| A00093 | 35222075 | Front Physiol | MicroRNA-122-5p Inhibition Improves Inflammation and Oxidative Stress Damage in Dietary-Induced Non-alcoholic Fatty Liver Disease Through Targeting FOXO3. | Details |
| A00100 | 35220131 | Phytomedicine | 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glucoside ameliorates NAFLD via attenuating hepatic steatosis through inhibiting mitochondrial dysfunction dependent on SIRT5. | Details |
| A00128 | 35212995 | Methods Mol Biol | Single Cell RNA Sequencing in NASH. | Details |
| A00148 | 35208265 | Metabolites | Plasma Oxylipin Profile Discriminates Ethnicities in Subjects with Non-Alcoholic Steatohepatitis: An Exploratory Analysis. | Details |
| A00157 | 35204710 | Biomolecules | Posttranscriptional Regulation of Insulin Resistance: Implications for Metabolic Diseases. | Details |
| A00160 | 35204232 | Antioxidants (Basel) | Dietary Selenium Alleviated Mouse Liver Oxidative Stress and NAFLD Induced by Obesity by Regulating the KEAP1/NRF2 Pathway. | Details |
| A00161 | 35204113 | Antioxidants (Basel) | Effects of Colchicine in a Rat Model of Diet-Induced Hyperlipidemia. | Details |
| A00162 | 35203687 | Biomedicines | A Novel 2-Hit Zebrafish Model to Study Early Pathogenesis of Non-Alcoholic Fatty Liver Disease. | Details |
| A00174 | 35198905 | iScience | Deletion of RNF186 expression suppresses diet-induced hepatic steatosis by regulating insulin activity. | Details |
| A00179 | 35196511 | Am J Med Sci | Deciphering the Role of Aquaporins in Metabolic Diseases: A Mini Review. | Details |
| A00203 | 35187967 | Exp Biol Med (Maywood) | Iron-accumulating splenocytes may exacerbate non-alcoholic steatohepatitis through the production of proinflammatory cytokines and reactive oxygen species. | Details |
| A00213 | 35182670 | J Ethnopharmacol | Gryllus bimaculatus De Geer hydrolysates alleviate lipid accumulation, inflammation, and endoplasmic reticulum stress in palmitic acid-treated human hepatoma G2 cells. | Details |
| A00235 | 35172845 | Nutr Metab (Lond) | Effects of exercise on high-fat diet-induced non-alcoholic fatty liver disease and lipid metabolism in ApoE knockout mice. | Details |