RTICBM-262(RTICBM-262) - 药物靶点：CB1R_在研适应症：可卡因相关疾病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Compound 3(Research Triangle Institute)

靶点

CB1R

作用方式

调节剂

作用机制

CB1调节剂(大麻素受体CB1调节剂)

治疗领域

其他疾病

在研适应症

可卡因相关疾病

非在研适应症-

原研机构

Research Triangle Institute

在研机构

Research Triangle Institute

非在研机构-

权益机构-

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/序列

分子式C18H14Cl2N2O2

InChIKeySMNYRHJGQPPNBC-UHFFFAOYSA-N

CAS号3019958-44-9

关联

100 项与 RTICBM-262 相关的临床结果

登录后查看更多信息

100 项与 RTICBM-262 相关的转化医学

登录后查看更多信息

100 项与 RTICBM-262 相关的专利（医药）

登录后查看更多信息

1

项与 RTICBM-262 相关的文献（医药）

2025-04-24·Journal of Medicinal Chemistry

Development of Squaramides as Allosteric Modulators of the CB₁ Receptor: Synthesis, Computational Studies, Biological Characterization, and Effects against Cocaine-Induced Behavioral Sensitization and Reinstatement in Rats

Article

作者: Nguyen, Thuy ; Barrus, Daniel G. ; Decker, Ann M. ; Harris, Danni L. ; Zhang, Yanan ; Gamage, Thomas F. ; Song, Chi Hyuck ; Li, Jun-Xu ; Liu, Jianfeng

Cannabinoid receptor type 1 (CB₁) negative allosteric modulators have emerged as an alternate approach to CB₁ orthosteric antagonists/inverse agonists for cocaine addiction treatment. This study explores aryl-alkyl squaramides as CB₁ allosteric modulators, featuring RTICBM-262 (3) with good in vitro potencies in CB₁ calcium mobilization, [³⁵S]GTPγS binding, and cAMP assays. Molecular modeling studies suggest 3 bound in a similar pocket as Org27569, forming π-stacking with key residues H154^2.41 and W241^4.50, and the potential C98-C107 disulfide bond had limited impact on its binding or receptor activation. ADME and in vivo pharmacokinetic studies suggest that 3 had reasonable metabolic stability, brain penetration, and selectivity against a panel of ∼ 50 targets but poor solubility and high protein binding. At 5.6 mg/kg (i.p.), 3 significantly attenuated both cocaine-seeking behavior specific to cue-induced reinstatement and cocaine-induced behavioral sensitization without altering locomotor activity. These results support squaramides as promising candidates for further investigation for cocaine addiction treatment.

100 项与 RTICBM-262 相关的药物交易

登录后查看更多信息