PRE-084 Hydrochloride

PRE-084 is a high affinity sigma receptor 1 (σ1) agonist. It shows Ki values of 2.2 and 13,091 nM for σ1 and σ2 receptors, respectively and an IC₅₀ of 44 nM in the sigma receptor assay. It does not show significant activity for PCP and other receptors (IC₅₀ > 10,000 nM). PRE-084 has beneficial effects in a cellular model of Huntington's disease. It (0.3 μM) decreases the deleterious effects of N-terminal mutant huntington proteins in neuronal PC6.3 cells by activating NF-κB pathway and decreasing oxidative stress. Modulators of sigma receptor 1 may be beneficial against SARS-CoV-2 based on interaction of sigma receptors with SARS-CoV-2 protein Nsp6.