The G Protein Signal-Biased Compound TRV130; Structures, Its Site of Action and Clinical Studies

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.

Cite this article as:

Miyano Kanako , Manabe Sei , Komatsu Akane , Fujii Yuriko , Mizobuchi Yusuke , Uezono Eiko , Ohshima Kaori , Nonaka Miki , Kuroda Yui , Narita Minoru and Uezono Yasuhito *, The G Protein Signal-Biased Compound TRV130; Structures, Its Site of Action and Clinical Studies, Current Topics in Medicinal Chemistry 2020; 20 (31) . https://dx.doi.org/10.2174/1568026620999201027224229