Validation of ACTOne CB1 and CB2 Assays, Subsequent Characterization of SMM-189, and Development and Characterization of New CB2 Inverse Agonists

Author

Chaela Sickbert Presley, University of Tennessee Health Science Center

Date of Award

12-2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program

Pharmaceutical Sciences

Track

Pharmaceutics

Research Advisor

Bob M. Moore, II, Ph.D.

Committee

Matthew Ennis, Ph.D. Vivian Lovless, Pharm.D. Anton Reiner, Ph.D. Joseph Swanson, Ph.D.

Keywords

cannabinoids, CB1, CB2, inverse agonist, microglia, triaryl

Abstract

Cannabinoids have emerged on the national scene as a promising untapped therapeutic class. In pursuit of development of cannabinoids for pharmacologic use, I established and validated two high-throughput in vitro pharmacological screening systems, the ACTOne cannabinoid 1 and cannabinoid 2 assays, to aid in evaluating cannabinoid compounds for receptor affinity, pharmacologic potency and efficacy, and for selected compounds, antagonist activity. Our lead compound, SMM-189, was evaluated using the ACTOne assays and determined to be a CB2 inverse agonist. Further investigation revealed SMM-189 to exert anti-inflammatory effects on the brain’s immune cells, microglia, through polarization to a pro-wound healing state. Next generation analogs of SMM-189 were also evaluated in the ACTOne assays in the hopes of developing a molecule with improved biochemical characteristics.

ORCID

http://orcid.org/0000-0001-6767-3996

DOI

10.21007/etd.cghs.2016.0416

Comments

Dissertation is under permanent embargo.

Recommended Citation

Presley, Chaela Sickbert (http://orcid.org/0000-0001-6767-3996), "Validation of ACTOne CB1 and CB2 Assays, Subsequent Characterization of SMM-189, and Development and Characterization of New CB2 Inverse Agonists" (2016). Theses and Dissertations (ETD). Paper 418. http://dx.doi.org/10.21007/etd.cghs.2016.0416.
https://dc.uthsc.edu/dissertations/418