Investigational Drug Details
| Drug ID: | D360 |
| Drug Name: | Telmisartan |
| Synonyms: | 4'-((1,4'-dimethyl-2'-propyl(2,6'-bi-1H-benzimidazol)-1'-yl)methyl)-(1,1'-biphenyl)-2-carboxylic acid; 4'-((4-methyl-6-(1-methyl-2-benzimidazolyl)-2-propyl-1-benzimidazolyl)methyl)-2-biphenylcarboxylic acid; 4'-[(1,4'-dimethyl-2'propyl[2,6'-bi-1H-benzimidazol]-1'-yl)methyl]-[1,1'-biphenyl]-2-carboxylic acid; 4'-[(1,7'-dimethyl-2'-propyl-1H,3'H-2,5'-bibenzimidazol-3'-yl)methyl]biphenyl-2-carboxylic acid; Telmisartan |
| Type: | Chemical drug |
| DrugBank ID: | DB00966 |
| DrugBank Description: | Telmisartan is an angiotensin II receptor antagonist (ARB) used in the management of hypertension. Generally, angiotensin II receptor blockers (ARBs) such as telmisartan bind to the angiotensin II type 1 (AT1) receptors with high affinity, causing inhibition of the action of angiotensin II on vascular smooth muscle, ultimately leading to a reduction in arterial blood pressure. Recent studies suggest that telmisartan may also have PPAR-gamma agonistic properties that could potentially confer beneficial metabolic effects. |
| PubChem ID: | 65999 |
| CasNo: | 144701-48-4 |
| Repositioning for NAFLD: | Yes |
| SMILES: | CCCC1=NC2=C(N1CC3=CC=C(C4=CC=CC=C4C(O)=O)C=C3)C=C(C5=NC6=CC=CC=C6N5C)C=C2C |
| Structure: |
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| InChiKey: | RMMXLENWKUUMAY-UHFFFAOYSA-N |
| Molecular Weight: | 514.629 |
| DrugBank Targets: | Type-1 angiotensin II receptor antagonist; Peroxisome proliferator-activated receptor gamma partial agonist |
| DrugBank MoA: | Telmisartan interferes with the binding of angiotensin II to the angiotensin II AT<sub>1</sub>-receptor by binding reversibly and selectively to the receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. Telmisartan does not inhibit the angiotensin converting enzyme, other hormone receptors, or ion channels. Studies also suggest that telmisartan is a partial agonist of PPARγ, which is an established target for antidiabetic drugs. This suggests that telmisartan can improve carbohydrate and lipid metabolism, as well as control insulin resistance without causing the side effects that are associated with full PPARγ activators. |
| DrugBank Pharmacology: | Telmisartan is an orally active nonpeptide angiotensin II antagonist that acts on the AT<sub>1</sub> receptor subtype. It has the highest affinity for the AT<sub>1</sub> receptor among commercially available ARBS and has minimal affinity for the AT<sub>2</sub> receptor. New studies suggest that telmisartan may also have PPARγ agonistic properties that could potentially confer beneficial metabolic effects, as PPARγ is a nuclear receptor that regulates specific gene transcription, and whose target genes are involved in the regulation of glucose and lipid metabolism, as well as anti-inflammatory responses. This observation is currently being explored in clinical trials. Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Telmisartan works by blocking the vasoconstrictor and aldosterone secretory effects of angiotensin II. |
| DrugBank Indication: | Used alone or in combination with other classes of antihypertensives for the treatment of hypertension. Also used in the treatment of diabetic nephropathy in hypertensive patients with type 2 diabetes mellitus, as well as the treatment of congestive heart failure (only in patients who cannot tolerate ACE inhibitors). |
| Targets: | PPARG partial agonist |
| Therapeutic Category: | Improve insulin resistance |
| Clinical Trial Progress: | Clinical trial on-going (NCT02213224) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0029 | NCT02213224 | Phase 4 | Unknown status | No Results Available | August 2014 | August 11, 2014 | Details |
| L0594 | JPRN-UMIN000020537 | Not selected | Recruiting | No Results Available | 12/01/2016 | 2 April 2019 | Details |
| L0628 | ChiCTR-TRC-14005028 | Phase 1 | Recruiting | No Results Available | 30/07/2014 | 18 April 2017 | Details |
| L0686 | JPRN-UMIN000001587 | Not selected | -- | No Results Available | 25/12/2008 | 2 April 2019 | Details |
| L0698 | ACTRN12606000411549 | Phase 2 | Not Recruiting | No Results Available | 20/09/2006 | 13 January 2020 | Details |
| L0963 | EUCTR2009-015703-13-DE | Not applicable | Not Recruiting | No Results Available | 02/11/2009 | 17 December 2012 | Details |
| L0965 | JPRN-UMIN000002641 | Not applicable | Recruiting | No Results Available | 21/10/2009 | 2 April 2019 | Details |
| L0981 | JPRN-UMIN000000540 | Not selected | Not Recruiting | No Results Available | 10/12/2006 | 2 April 2019 | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A04567 | 33578449 | Biotechnol Appl Biochem | An insight into the role of telmisartan as PPAR-γ/α dual activator in the management of nonalcoholic fatty liver disease. | Details |
| A06304 | 32934967 | J Biol Methods | An in vitro model of hepatic steatosis using lipid loaded induced pluripotent stem cell derived hepatocyte like cells. | Details |
| A06679 | 32782954 | JGH Open | Effect of telmisartan and vitamin E on liver histopathology with non-alcoholic steatohepatitis: A randomized, open-label, noninferiority trial. | Details |
| A11195 | 31004566 | Biochem Pharmacol | Telmisartan and/or chlorogenic acid attenuates fructose-induced non-alcoholic fatty liver disease in rats: Implications of cross-talk between angiotensin, the sphingosine kinase/sphingoine-1-phosphate pathway, and TLR4 receptors. | Details |
| A11542 | 30850637 | Sci Rep | Connectivity mapping of angiotensin-PPAR interactions involved in the amelioration of non-alcoholic steatohepatitis by Telmisartan. | Details |
| A12660 | 30341231 | Postgrad Med J | Pharmacological interventions for non-alcoholic fatty liver disease: a systematic review and network meta-analysis. | Details |
| A14009 | 29636553 | Hypertens Res | The role of the angiotensin II type I receptor blocker telmisartan in the treatment of non-alcoholic fatty liver disease: a brief review. | Details |
| A15335 | 28962213 | Exp Ther Med | Effects of telmisartan on improving leptin resistance and inhibiting hepatic fibrosis in rats with non-alcoholic fatty liver disease. | Details |
| A18521 | 27074921 | Dig Dis Sci | Treatment with Oxidized Phospholipids Directly Inhibits Nonalcoholic Steatohepatitis and Liver Fibrosis Without Affecting Steatosis. | Details |
| A18625 | 27028410 | Liver Int | Lipid disorder and intrahepatic renin-angiotensin system activation synergistically contribute to non-alcoholic fatty liver disease. | Details |
| A18986 | 26831610 | Saudi J Gastroenterol | Effect of telmisartan on histological activity and fibrosis of non-alcoholic steatohepatitis: A 1-year randomized control trial. | Details |
| A20136 | 26133820 | Zhonghua Gan Zang Bing Za Zhi | [Effects of telmisartan on resistin expression in a rat model of nonalcoholic steatohepatitis and insulin resistance]. | Details |
| A22700 | 25796814 | Wiad Lek | Combined effect of appointment telmisartan and atorvastatin on hemodynamic indicators and the indicators of lipid profile in patients with arterial hypertension combined with obesity and steatohepatitis. | Details |
| A23089 | 24048504 | Med Mol Morphol | Linagliptin alleviates hepatic steatosis and inflammation in a mouse model of non-alcoholic steatohepatitis. | Details |
| A23157 | 23997767 | Int J Endocrinol | Effect of Telmisartan or Losartan for Treatment of Nonalcoholic Fatty Liver Disease: Fatty Liver Protection Trial by Telmisartan or Losartan Study (FANTASY). | Details |
| A23694 | 23560443 | Int J Exp Pathol | Inhibition of Glutaminyl Cyclases alleviates CCL2-mediated inflammation of non-alcoholic fatty liver disease in mice. | Details |
| A24444 | 22886508 | J Gastroenterol | Angiotensin II type 1 receptor antagonist prevents hepatic carcinoma in rats with nonalcoholic steatohepatitis. | Details |
| A25133 | 22152320 | Zhonghua Gan Zang Bing Za Zhi | [Effects of telmisartan on nonalcoholic steatohepatitis rat model by activating peroxisome proliferator-activated receptor r]. | Details |
| A25920 | 21327395 | Cell Tissue Res | Telmisartan improves nonalcoholic steatohepatitis in medaka (Oryzias latipes) by reducing macrophage infiltration and fat accumulation. | Details |
| A26370 | 20578268 | Hepatology | A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. | Details |