Delving into the Latest Updates on PB28 with Synapse

Overview

Basic Info

Drug Type

Chemical drugs

Synonyms-

Target

σ2 receptor

Mechanism

σ2 receptor agonists(Sigma-2 receptor agonists)

Therapeutic Areas-

Active Indication-

Inactive Indication-

Originator Organization

University of Bari

Active Organization

University of Bari

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

The sigma-1 receptor (σ1-R) and sigma-2 receptor (σ2-R) are potential drug targets for treatment of cancer, pain, depression, retinal degeneration and other neuronal diseases. Previous reports show that sigma-1 receptor modulates the activities of multiple channels. We are interested in possible sigma receptor modulation of Kv2.1, a K⁺ channel abundant in retinal photoreceptors. We tested the effect of established sigma receptor ligands on Kv2.1 channels which were stably expressed in HEK293 cells. Surprisingly, σ1-R antagonists inhibited Kv2.1 currents in both wild type and σ1-R knockout HEK293 cells that we engineered using the CRISPR/Cas9 technology. Moreover, PB28, a σ1-R antagonist and also σ2-R agonist, inhibited Kv2.1 in σ1-R knockout cells, but this action was not blocked by the σ2-R antagonists that did not have an effect on Kv2.1. We also observed inhibition of electroretinogram by PB28 in wild type as well as σ1-R knockout mice. Thus, the results in this study indicate that the Kv2.1-inhibiting function of the sigma ligands is not sigma receptor dependent, suggesting a direct effect of these ligands on the Kv2.1 channel.

100 Deals associated with PB28

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