Rational design of cannabinoid type-1 receptor allosteric modulators: Org27569 and PSNCBAM-1 hybrids.

ABSTRACT: Allosteric modulation offers an alternate approach to target the cannabinoid type-1 receptor (CB₁) for therapeutic benefits. Examination of the two widely studied prototypic CB₁ negative allosteric modulators (NAMs) Org27569 and PSNCBAM-1 revealed structural resemblance and similar structure-activity relationships (SARs). In silico docking and dynamics simulation studies using the crystal structure of CB₁ co-bound with CP55,940 and Org27569 suggested that Org27569 and PSNCBAM-1 occupied the same binding pocket and several common interactions were present in both series with the CB₁ receptor. A new scaffold was therefore designed by merging the key structural features from the two series and the hybrids retained these binding features in the in si

SUBMITTER: Nguyen T 

PROVIDER: S-EPMC8506265 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature