Investigational Drug Details
| Drug ID: | D209 |
| Drug Name: | Losartan |
| Synonyms: | (2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazol-5-yl)methanol; 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole; Losartan |
| Type: | Chemical drug |
| DrugBank ID: | DB00678 |
| DrugBank Description: | Losartan is an angiotensin II receptor blocker (ARB) used to treat hypertension. Angiotensin-converting enzyme (ACE) inhibitors are used for a similar indication but are associated with a cough. When patients with ACE inhibitor associated coughs are switched to ARBs like losartan, they have an incidence of cough similar to placebo or . Losartan is available as losartan potassium oral tablets as well as a combination tablet of losartan potassium and hydrochlorothiazide. Patients taking losartan should have their renal function and potassium levels monitored. Losartan was granted FDA approval on 14 April 1995. |
| PubChem ID: | 3961 |
| CasNo: | 114798-26-4 |
| Repositioning for NAFLD: | Yes |
| SMILES: | C(n1c(CCCC)nc(c1CO)Cl)c1ccc(cc1)c1c(cccc1)c1[nH]nnn1 |
| Structure: |
|
| InChiKey: | PSIFNNKUMBGKDQ-UHFFFAOYSA-N |
| Molecular Weight: | 422.92 |
| DrugBank Targets: | Type-1 angiotensin II receptor antagonist |
| DrugBank MoA: | Losartan reversibly and competitively prevents angiotensin II binding to the AT<sub>1</sub> receptor in tissues like vascular smooth muscle and the adrenal gland. Losartan and its active metabolite bind the AT<sub>1</sub> receptor with 1000 times more affinity than they bind to the AT<sub>2</sub> receptor. The active metabolite of losartan is 10-40 times more potent by weight than unmetabolized losartan as an inhibitor of AT<sub>1</sub> and is a non-competitive inhibitor. Losartan's prevention of angiotensin II binding causes vascular smooth muscle relaxation, lowering blood pressure. Angiotensin II would otherwise bind to the AT<sub>1</sub> receptor and induce vasoconstriction, raising blood pressure. |
| DrugBank Pharmacology: | Losartan is an angiotensin II receptor blocker used to treat hypertension, diabetic nephropathy, and to reduce the risk of stroke. Losartan has a long duration of action as it is given once daily. Patients taking losartan should be regularly monitored for hypotension, renal function, and potassium levels. |
| DrugBank Indication: | Losartan is indicated to treat hypertension in patients older than 6 years, reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy (though this benefit may not extend to patients with African heritage), and to treat diabetic nephropathy with elevated serum creatinine and proteinuria in patients with type 2 diabetes and hypertension. Losartan with hydrochlorothiazide is indicated to treat hypertension and to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy (though this benefit may not extend to patients with African heritage). |
| Targets: | AGTR1 antagonist&binder |
| Therapeutic Category: | Anti-fibrosis |
| Clinical Trial Progress: | Phase 3 on-going (IRCT20180412039283N1) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0077 | NCT03467217 | Phase 2 | Terminated | Has Results | October 2, 2018 | October 21, 2021 | Details |
| L0125 | NCT00699036 | Phase 2 | Unknown status | No Results Available | April 2007 | June 19, 2009 | Details |
| L0185 | NCT01913470 | Phase 2 | Completed | Has Results | July 2013 | May 15, 2017 | Details |
| L0267 | NCT01051219 | Phase 3 | Completed | No Results Available | May 2011 | October 7, 2015 | Details |
| L0388 | ChiCTR2100044996 | Not applicable | Recruiting | No Results Available | 03/04/2021 | 2 November 2021 | Details |
| L0395 | IRCT20180412039283N1 | Phase 3 | Not Recruiting | No Results Available | 16/02/2021 | 22 February 2021 | Details |
| L0510 | IRCT20161210031316N2 | Phase 3 | Not Recruiting | No Results Available | 13/02/2018 | 26 March 2018 | Details |
| L0535 | ISRCTN57849521 | Phase 3 | Not Recruiting | No Results Available | 12/10/2009 | 22 May 2017 | Details |
| L0572 | IRCT2016060628305N1 | Phase 2/Phase 3 | Not Recruiting | No Results Available | 14/08/2016 | 22 February 2018 | Details |
| L0674 | EUCTR2009-015166-62-GB | Phase 3 | Not Recruiting | Has Results | 08/10/2010 | 30 June 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 | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | 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 | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A00329 | 35133671 | Hepatology | Randomized placebo-controlled trial of losartan for pediatric NAFLD. | Details |
| A01605 | 34681219 | Pharmaceuticals (Basel) | Antiangiogenic Drugs in NASH: Evidence of a Possible New Therapeutic Approach. | Details |
| A02473 | 34360607 | Int J Mol Sci | Losartan Prevents Hepatic Steatosis and Macrophage Polarization by Inhibiting HIF-1α in a Murine Model of NAFLD. | Details |
| A09801 | 31604805 | J Lipid Res | Angiotensinogen in hepatocytes contributes to Western diet-induced liver steatosis. | Details |
| A13409 | 29992039 | Pilot Feasibility Stud | A randomized, controlled, crossover pilot study of losartan for pediatric nonalcoholic fatty liver disease. | Details |
| A15287 | 28986475 | Drug Metab Dispos | Pediatric Cytochrome P450 Activity Alterations in Nonalcoholic Steatohepatitis. | Details |
| A15877 | 28676018 | Curr Vasc Pharmacol | Can Serum Uric Acid Lowering Therapy Contribute to the Prevention or Treatment of Nonalcoholic Fatty Liver Disease? | Details |
| A16398 | 28419124 | PLoS One | A randomised controlled trial of losartan as an anti-fibrotic agent in non-alcoholic steatohepatitis. | Details |
| A16707 | 28231800 | Lipids Health Dis | Dietary intervention, but not losartan, completely reverses non-alcoholic steatohepatitis in obese and insulin resistant mice. | Details |
| A17620 | 27712037 | J Biochem Mol Toxicol | In vivo cytochrome P450 activity alterations in diabetic nonalcoholic steatohepatitis mice. | Details |
| A19020 | 26817117 | Eksp Klin Gastroenterol | [COMPARISON OF DIFFERENT TREATMENT REGIMENS IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE]. | Details |
| A22495 | 24517411 | Metab Syndr Relat Disord | Comparative effects of the renin-angiotensin system blockers on nonalcoholic fatty liver disease and insulin resistance in C57BL/6 mice. | Details |
| A22931 | 24197250 | J Gastroenterol | Combination of sorafenib and angiotensin-II receptor blocker attenuates preneoplastic lesion development in a non-diabetic rat model of 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 |
| A23310 | 23875703 | Clin Sci (Lond) | Involvement of the HIF-1α and Wnt/β-catenin pathways in the protective effects of losartan on fatty liver graft with ischaemia/reperfusion injury. | Details |
| A24014 | 23301938 | J Gastroenterol Hepatol | Cross talk between toll-like receptor-4 signaling and angiotensin-II in liver fibrosis development in the rat model of non-alcoholic steatohepatitis. | Details |
| A25518 | 21748770 | Hepatology | Rosiglitazone versus rosiglitazone and metformin versus rosiglitazone and losartan in the treatment of nonalcoholic steatohepatitis in humans: a 12-month randomized, prospective, open- label trial. | Details |
| A25872 | 21372165 | Am J Physiol Gastrointest Liver Physiol | Combination treatment of angiotensin II type I receptor blocker and new oral iron chelator attenuates progression of nonalcoholic steatohepatitis in rats. | Details |
| A26788 | 19782079 | Gastroenterology | Modulation of hepatic fibrosis by c-Jun-N-terminal kinase inhibition. | Details |
| A27065 | 19230890 | Atherosclerosis | Losartan reduces liver expression of plasminogen activator inhibitor-1 (PAI-1) in a high fat-induced rat nonalcoholic fatty liver disease model. | Details |