Delving into the Latest Updates on RTICBM-262 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Compound 3(Research Triangle Institute)

Target

CB1R

Action

modulators

Mechanism

CB1 modulators(Cannabinoid CB1 receptor modulators)

Therapeutic Areas

Other Diseases

Active Indication

Cocaine-Related Disorders

Inactive Indication-

Originator Organization

Research Triangle Institute

Active Organization

Research Triangle Institute

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC18H14Cl2N2O2

InChIKeySMNYRHJGQPPNBC-UHFFFAOYSA-N

CAS Registry3019958-44-9

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 Deals associated with RTICBM-262

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