Structure-guided drug discovery for novel modulators of cannabinoid receptors

Cannabinoid receptor subtypes 1 and 2 (CB1 and CB2) are G protein coupled receptors (GPCRs) and potential therapeutic targets for three of the most common and debilitating service-related conditions: chronic pain, post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI).

The purpose of this research is to develop subtype-selective modulators for CB1 and CB2 that can be used for the treatment of chronic pain, PTSD and TBI.

The success of this project will provide new tool compounds for the identification of distinct CB signaling pathways and potential therapies for medical conditions.

The project will be initiated by screening compounds from DNA encoding chemical library containing billions of small molecules, followed by functional characterization,structural determination of complex by cryo-electron microscopy and structure-based chemical optimization.

The lead PIs for the project are Brian Kobilka (Stanford University) and collaborating investigator Alex Makriyannis (Northeastern University), and I will be the major executor.

This project is planned to finish within three years, aiming at identifying three promising compounds for each receptor (CB1 and CB2).