# Structure and Function of CB2 Receptor

> **NIH NIH R01** · NORTHEASTERN UNIVERSITY · 2021 · $763,601

## Abstract

PROJECT SUMMARY
The central focus of this Multi-PI R01 research proposal is the structure-function characterization of the human
cannabinoid receptor 2 (CB2), a key protein component of the endocannabinoid system. We aim to develop
a fundamental understanding of the structural basis of CB2 function, with the ultimate translational goal of
establishing a robust structure-based drug design (SBDD) program. The ECS is a complex network of lipid
ligands, receptors, and metabolic enzymes involved in a wide range of important physiological processes.
There have been important implications that targeting CB2 may be useful as a means for treating
inflammation, pain, neurological disorders and addiction. As with other G protein-coupled receptors
(GPCRs), CB2 can exhibit preferential signaling events in response to different ligands. This functional
selectivity offers the opportunity to refine therapeutic approaches, to improve beneficial properties, and
reduce side effect liability. The study will provide the structural basis for the design and development of
pharmacologically distinct CB2-selective compounds as useful biological probes and/or leads for the
future development of therapeutics. To enhance our effort in obtaining high quality crystal structures, we shall
use carefully designed ligands with high affinities and selectivities for CB2, and which are also capable of
tight attachment at or near the receptor’s binding domain(s) coupled with their abilities to form crystallizable
ligand-receptor complexes. The study has three specific aims: (1) Design and synthesize novel irreversible
ligands representing key classes of CB2 selective compounds with distinct functional profiles. (2) Extensive
characterization of the newly synthesized ligands in order to identify compounds with pharmacologically
diverse profiles, including the partial agonists, inverse agonists, neutral antagonists and allosteric
modulators. The crystallization candidates and their chemical derivatives will also be characterized for their
reversible binding nature using functional assays. (3) Develop a clear understanding of CB2 ligand binding
sites by determining the 3-D structures of the several receptor-ligand complexes. Towards these goals,
several crystal structures will be solved to better understand molecular recognition, signaling, and to assist in
the design of novel compounds that could then serve as prototypes for later generation leads and drug
candidates.

## Key facts

- **NIH application ID:** 10245042
- **Project number:** 5R01DA045020-05
- **Recipient organization:** NORTHEASTERN UNIVERSITY
- **Principal Investigator:** Laura M. Bohn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $763,601
- **Award type:** 5
- **Project period:** 2017-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10245042

## Citation

> US National Institutes of Health, RePORTER application 10245042, Structure and Function of CB2 Receptor (5R01DA045020-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10245042. Licensed CC0.

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