Title:The G Protein Signal-Biased Compound TRV130; Structures, Its Site of Action and Clinical Studies
Volume: 20
Issue: 31
Author(s): Kanako Miyano, Sei Manabe, Akane Komatsu, Yuriko Fujii, Yusuke Mizobuchi, Eiko Uezono, Kaori Ohshima, Miki Nonaka, Yui Kuroda, Minoru Narita and Yasuhito Uezono*
Affiliation:
- Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo,Japan
Keywords:
μ Opioid receptors, TRV130, Oliceridine, Biased ligands, Adverse β-arrestin effects, Agonists.
Abstract: Opioid agonists elicit their analgesic action mainly via μ opioid receptors; however, their use
is limited because of adverse events including constipation and respiratory depression. It has been
shown that analgesic action is transduced by the G protein-mediated pathway whereas adverse events
are by the β-arrestin-mediated pathway through μ opioid receptor signaling. The first new-generation
opioid TRV130, which preferentially activates G protein- but not β-arrestin-mediated signal, was constructed
and developed to reduce adverse events. TRV130 and other G protein-biased compounds tend
to elicit desirable analgesic action with less adverse effects. In clinical trials, the intravenous TRV130
(oliceridine) was evaluated in Phase I, II and III clinical studies. Here we review the discovery and synthesis
of TRV130, its main action as a novel analgesic having less adverse events, its up-to-date status in
clinical trials, and additional concerns about TRV130 as demonstrated in the literature.
