Trevena has announced the publication of new findings related to the mechanism of action of its Angiotensin II Type 1 Receptor (AT1R) biased ligands. The publication describes work led by R John Solaro, head of the Department of Physiology and Biophysics at the University of Illinois, Chicago, USA, performed in collaboration with Trevena scientists.
The studies evaluated the molecular mechanisms of action for TRV120023, a molecule closely related to Trevena’s clinical stage asset, TRV027, which is in phase 2 testing for the treatment of acute heart failure.
The article, entitled “The beta-arrestin-biased ligand TRV120023 inhibits angiotensin II-induced cardiac hypertrophy while preserving enhanced myofilament response to calcium”, was published online, ahead of print, in the American Journal of Physiology – Heart and Circulatory Physiology.
Solaro’s work showed that TRV120023 blocked cardiac hypertrophy in rats, while stimulating biochemical pathways linked to increased cardiac contractility. TRV120023 increased the sensitivity of cardiac myofilaments to calcium, suggesting that TRV120023 and molecules like it, such as TRV027, can increase cardiac contractile force (inotropy) through a mechanism distinct from classic inotropes, which are associated with cardiac arrhythmia and increased mortality. Solaro said: “These experiments suggest that Trevena’s biased ligands regulate the heart’s contractile machinery through a novel mechanism which may simultaneously block cardiac dysfunction while promoting cardiac contractility.”