Therapeutic Strategy Details
| Strategy ID: | S03 |
| Strategy: | Anti-fibrosis |
| Other Terms: | fibrosis |
| Related Targets: | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant |
| Related Drugs: | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 |
| Mechanism: | Fibroblast growth factor (FGF) 1 demonstrated protection against nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic and obese mice by an uncertain mechanism. In a longitudinal study of patients with NAFLD, fibrosis stage, but no other histologic features of steatohepatitis, were associated independently with long-term overall mortality, liver transplantation, and liver-related events. |
| Reference (PMIDs): | 27061197; 32965675; 25935633 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T01 | 5'-AMP-activated protein kinase subunit beta-1 | PRKAB1 | activator | Kinase | Q9Y478 | AAKB1_HUMAN | Details |
| T07 | Bile acid receptor | NR1H4 | agonist | Nuclear hormone receptor | Q96RI1 | NR1H4_HUMAN | Details |
| T09 | Toll-like receptor 4 | TLR4 | antagonist | Membrane receptor | O00206 | TLR4_HUMAN | Details |
| T10 | Caspase-1 | CASP1 | inhibitor | Enzyme | P29466 | CASP1_HUMAN | Details |
| T11 | Caspase-3 | CASP3 | inhibitor | Enzyme | P42574 | CASP3_HUMAN | Details |
| T13 | Apoptosis Signal-regulating Kinase 1 | ASK1 | inhibitor | Enzyme | Q99683 | M3K5_HUMAN | Details |
| T23 | Type-1 angiotensin II receptor | AGTR1 | antagonist | GPCR | P30556 | AGTR1_HUMAN | Details |
| T38 | Caspase-4 | Casp4 | inhibitor | Enzyme | P49662 | CASP4_HUMAN | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D005 | Aldafermin | Biological drug | DB16086 | FGF19 analog | Anti-fibrosis | Under clinical trials | Details |
| D008 | Alpha-tocopherol | Chemical drug | DB00163 | NR1I2; ALOX5; DGKA | -- | Under clinical trials | Details |
| D028 | Belapectin | Chemical drug | DB15125 | Gelactin-3 inhibitor; LGALS3 inhibitor | Anti-fibrosis | Failed in clinical trials | Details |
| D045 | BLD-0409 | Miscellany | -- | ENPP2 inhibitor; ATX inhibitor | Anti-fibrosis | Under clinical trials | Details |
| D046 | Pegbelfermin | Biological drug | DB15365 | FGF21 analog | Improve insulin resistance; Enhance lipid metabolism; Anti-fibrosis | Under clinical trials | Details |
| D068 | Cenicriviroc | Chemical drug | DB11758 | CCR2 inhibitor; CCR5 inhibitor | Anti-fibrosis | Failed in clinical trials | Details |
| D122 | Empagliflozin | Chemical drug | DB09038 | SLC5A2 inhibitor; SGLT-2 inhibitor | Improve insulin resistance | Under clinical trials | Details |
| D123 | Emricasan | Chemical drug | DB05408 | caspase inhibitor | Anti-inflammatory | Failed in clinical trials | Details |
| D134 | Fenretinide | Chemical drug | DB05076 | RARB agonist; RARG agonist | Anti-fibrosis | Under clinical trials | Details |
| D136 | Firsocostat | Chemical drug | DB16166 | ACC inhibitor | Enhance lipid metabolism | 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 |
| R0046 | DB00138 | approved; nutraceutical | small molecule | Cystine | Therapeutic strategy associated | Details |
| R0056 | DB00159 | approved; nutraceutical | small molecule | Icosapent | Therapeutic strategy associated | Details |
| R0059 | DB00171 | investigational; nutraceutical | small molecule | ATP | Indication associated | Details |
| R0065 | DB00178 | approved | small molecule | Ramipril | Therapeutic strategy associated | Details |
| R0081 | DB00214 | approved | small molecule | Torasemide | Therapeutic strategy associated | Details |
| R0238 | DB00684 | approved; investigational | small molecule | Tobramycin | Indication associated | Details |
| R0239 | DB00688 | approved; investigational | small molecule | Mycophenolate mofetil | Therapeutic strategy associated | Details |
| R0262 | DB00742 | approved; investigational | small molecule | Mannitol | Therapeutic strategy associated | Details |
| R0285 | DB00803 | approved | small molecule | Colistin | Therapeutic strategy associated | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A00001 | 35259705 | Diabetes Metab Syndr | Role of diabetologists in the management of nonalcoholic fatty liver disease: Primary prevention and screening/management of fibrosis and cirrhosis. | Details |
| A00010 | 35255811 | BMC Gastroenterol | The effect of daily consumption of probiotic yogurt on liver enzymes, steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD): study protocol for a randomized clinical trial. | Details |
| A00016 | 35252828 | JHEP Rep | Macrophage MerTK promotes profibrogenic cross-talk with hepatic stellate cells via soluble mediators. | Details |
| A00020 | 35251901 | Australas J Ultrasound Med | Portal Venous Pulsatility Index as a predictor of fibrosis in patients with non-alcoholic fatty liver disease. | Details |
| A00031 | 35250588 | Front Pharmacol | Platelets in Non-alcoholic Fatty Liver Disease. | Details |
| A00032 | 35250014 | Ultrasound Q | Clinical Feasibility of Shear Wave Dispersion Slope for Noninvasive Diagnosis of Nonalcoholic Steatohepatitis in Patients With Morbid Obesity: Preliminary Results Using US Shear Wave Elastography. | Details |
| A00047 | 35244676 | Am J Clin Nutr | Sex-related association of NAFLD and liver fibrosis with body fat distribution in the general US population. | Details |
| A00049 | 35243280 | JHEP Rep | Cellular origins of regenerating liver and hepatocellular carcinoma. | Details |
| A00056 | 35240344 | Cell Mol Gastroenterol Hepatol | Activation of Liver mTORC1 Protects Against NASH via Dual Regulation of VLDL-TAG Secretion and De Novo Lipogenesis. | Details |
| A00058 | 35238782 | Turk J Gastroenterol | Evaluation of Magnetic Resonance Elastography and Transient Elastography for Liver Fibrosis and Steatosis Assessments in the Liver Transplant Setting. | Details |
| A00059 | 35238641 | Proc Natl Acad Sci U S A | Disruption of the circadian clock component BMAL1 elicits an endocrine adaption impacting on insulin sensitivity and liver disease. | Details |
| A00061 | 35236351 | Lipids Health Dis | Circulating chemerin levels in metabolic-associated fatty liver disease: a systematic review and meta-analysis. | Details |
| A00069 | 35232986 | Sci Rep | Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation. | Details |
| A00081 | 35227956 | Clin Res Hepatol Gastroenterol | Abnormal liver tests and non-alcoholic fatty liver disease predict disease progression and outcome of patients with Covid-19. | Details |
| A00083 | 35226932 | Ultraschall Med | Point Shear Wave Elastography by ElastPQ for Fibrosis Screening in Patients with NAFLD: A Prospective, Multicenter Comparison to Vibration-Controlled Elastography. | Details |
| A00088 | 35223941 | Front Nutr | Cumulative Betel Quid Chewing and the Risk of Significant Liver Fibrosis in Subjects With and Without Metabolic Syndrome. | Details |
| A00089 | 35223701 | Front Pediatr | Association Between Non-invasive Diagnostic Methods of Liver Fibrosis and Type 2 Diabetes in Pediatric Patients With Non-alcoholic Fatty Liver Disease. | Details |
| A00091 | 35222903 | Ther Adv Chronic Dis | Nicotinamide supplementation in diabetic nonalcoholic fatty liver disease patients: randomized controlled trial. | Details |
| A00097 | 35220673 | Liver Int | Knowledge of liver fibrosis stage among adults with NAFLD/NASH improves adherence to lifestyle changes. | Details |
| A00099 | 35220605 | Hepatology | Metabolic subtypes of nonalcoholic fatty liver disease patients exhibit distinctive cardiovascular risk profiles. | Details |