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Synonyms: TRV 120027 | TRV-027 | TRV-120027 | TRV120027
Compound class: Peptide or derivative
Comment: TRV027 (TRV120027) is a synthetic analogue of endogenous angiotensin II peptide . It acts as a β-arrestin biased ligand of the angiotensin II type 1 receptor (AT1R). TRV027 inhibits angiotensin II-mediated vasoconstriction, increases cardiomyocyte contractility and induces an anti-apoptotic effect, all of which when combined, provide a cardioprotective result.
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
|No information available.|
|Summary of Clinical Use|
|In vivo, the compound's action is cardioprotective [1-2], and was progressed to Phase 2 clinical trial (NCT01966601) in patients suffering from acute decompensated heart failure . First-in-human results from dosing in healthy volunteers were reported in 2012 . In 2017 it was reported that TRV027 therapy in patients with acute heart failure (AHF) did not improve clinical status through 30-day follow-up compared with placebo .
COVID-19: As the SARS-CoV-2 virus binds to ACE2 in the lungs, and effectively downregulates its normal function, levels of angiotensin II (ATII) increase. This drives overactivation of the AT1 receptor, and this likely contributes towards downstream acute lung injury. As a functional AT1 receptor antagonist, TRV027 has potential to reverse the effects of elevated ATII. A clinical trial of TRV027 (NCT04419610; Imperial College London) will be carried out to establish if antagonising the renin-angiotensin system has efficacy to combat acute lung injury and ARDS in COVID-19 patients. If successful this would offer an additional option to anti-virals and anti-inflammatory therapies to address the umet clinical need for treatments for this multi-system, multi-organ disease.
|Clinical Trial ID||Title||Type||Source||Comment||References|
|NCT01514578||Single Ascending Dose Study of Intravenous TRV130A in Healthy Adult Males||Phase 1 Interventional||Trevena Inc.||4|
|NCT04419610||RAS and Coagulopathy in COVID19||Early Phase 1 Interventional||Imperial College London||4|
|NCT00004030||VX-853 in Treating Patients With Solid Tumors Who Are Receiving Liposomal Doxorubicin||Phase 1/Phase 2 Interventional||Georgetown University||3|