Delving into the Latest Updates on AD-258 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

σ1 receptor x σ2 receptor

Mechanism

σ1 receptor modulators(Sigma opioid receptor modulators), σ2 receptor modulators(Sigma-2 receptor modulators)

Therapeutic Areas

Nervous System Diseases

Active Indication

Pain

Inactive Indication-

Originator Organization

University of Illinois

Active Organization

University of Catania

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC22H25N3

InChIKeyKURULBHGVNUVDX-UHFFFAOYSA-N

CAS Registry-

Author: Costanzo, Giuliana ; Ruiz-Cantero, M Carmen ; Costa, Giosuè ; Alcaro, Stefano ; Cobos, Enrique J ; Amata, Emanuele ; Pasquinucci, Lorella ; Cosentino, Giuseppe ; Shah, Dhara ; González-Cano, Rafael ; Son, Kyung No ; Dichiara, Maria ; Lombino, Jessica ; Coricello, Adriana ; Lee, Sang Min ; Aakalu, Vinay Kumar ; Ambrosio, Francesca Alessandra ; Marrazzo, Agostino

The design and synthesis of a series of 2,7-diazaspiro[4.4]nonane derivatives as potent sigma receptor (SR) ligands, associated with analgesic activity, are the focus of this work. In this study, affinities at S1R and S2R were measured, and molecular modeling studies were performed to investigate the binding pose characteristics. The most promising compounds were subjected to in vitro toxicity testing and subsequently screened for in vivo analgesic properties. Compound 9d (AD258) exhibited negligible in vitro cellular toxicity and a high binding affinity to both SRs (K_iS1R = 3.5 nM, K_iS2R = 2.6 nM), but not for other pain-related targets, and exerted high potency in a model of capsaicin-induced allodynia, reaching the maximum antiallodynic effect at very low doses (0.6-1.25 mg/kg). Functional activity experiments showed that S1R antagonism is needed for the effects of 9d and that it did not induce motor impairment. In addition, 9d exhibited a favorable pharmacokinetic profile.

100 Deals associated with AD-258

Login to view more data