AD-258(AD-258) - 药物靶点：σ1 receptor x σ2 receptor_在研适应症：疼痛_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

σ1 receptor x σ2 receptor

作用机制

σ1 receptor调节剂(σ-阿片受体调节剂)、σ2 receptor调节剂(Sigma-2受体调节剂)

治疗领域

神经系统疾病

在研适应症

疼痛

非在研适应症-

原研机构

University of Illinois

在研机构

University of Catania

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C22H25N3

InChIKeyKURULBHGVNUVDX-UHFFFAOYSA-N

CAS号-

关联

100 项与 AD-258 相关的临床结果

登录后查看更多信息

100 项与 AD-258 相关的转化医学

登录后查看更多信息

100 项与 AD-258 相关的专利（医药）

登录后查看更多信息

1

项与 AD-258 相关的文献（医药）

2023-08-24·Journal of medicinal chemistry1区 · 医学

Discovery of AD258 as a Sigma Receptor Ligand with Potent Antiallodynic Activity.

1区 · 医学

Article

作者: 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 项与 AD-258 相关的药物交易

登录后查看更多信息