Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators

Paula Morales; Chanté Muller; Nadine Jagerovic; Patricia H Reggio

doi:10.3389/fmolb.2022.841190

Targeting CB2 and TRPV1: Computational Approaches for the Identification of Dual Modulators

Front Mol Biosci. 2022 Feb 25:9:841190. doi: 10.3389/fmolb.2022.841190. eCollection 2022.

Authors

Paula Morales¹, Chanté Muller², Nadine Jagerovic¹, Patricia H Reggio²

Affiliations

¹ Medicinal Chemistry Institute, Spanish National Research Council, Madrid, Spain.
² Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, United States.

Abstract

Both metabotropic (CBRs) and ionotropic cannabinoid receptors (ICRs) have implications in a range of neurological disorders. The metabotropic canonical CBRs CB1 and CB2 are highly implicated in these pathological events. However, selective targeting at CB2 versus CB1 offers optimized pharmacology due to the absence of psychoactive outcomes. The ICR transient receptor potential vanilloid type 1 (TRPV1) has also been reported to play a role in CNS disorders. Thus, activation of both targets, CB2 and TRPV1, offers a promising polypharmacological strategy for the treatment of neurological events including analgesia and neuroprotection. This brief research report aims to identify chemotypes with a potential dual CB2/TRPV1 profile. For this purpose, we have rationalized key structural features for activation and performed virtual screening at both targets using curated chemical libraries.

Keywords: CB2; TRPV1; cannabinoids; dual ligands; ionotropic receptors; multitargeting.

Grants and funding

F31 DA053022/DA/NIDA NIH HHS/United States