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High-affinity sigma-1 (σ1) receptor ligands based on the σ1 antagonist PB212. Future Med Chem 2019 Oct;11(19):2547-2562



Pubmed ID




Scopus ID

2-s2.0-85073634435 (requires institutional sign-in at Scopus site)   6 Citations


Aim: The σ1 receptor is a druggable target involved in many physiological processes and diseases. To clarify its physiology and derive therapeutic benefit, nine analogs based on the σ1 antagonist PB212 were synthesized replacing the 4-methylpiperidine with basic moieties of varying size and degree of conformational freedom. Results & methodology: 3-Phenylpyrrolidine, 4-phenylpiperidine or granatane derivatives displayed the highest affinity (Ki.#x00A0;= 0.12, 0.31 or 1.03 nM). Calcium flux assays in MCF7σ1 cells indicated that the highest σ1 receptor affinity are σ1 antagonists. Molecular models provided a structural basis for understanding the σ1 affinity and functional activity of the analogs and incorporated Glennon's σ1 pharmacophore model. Conclusion: Herein, we identify new compounds exploitable as therapeutic drug leads or as tools to study σ1 receptor physiology.

Author List

Niso M, Mosier PD, Marottoli R, Ferorelli S, Cassano G, Gasparre G, Leopoldo M, Berardi F, Abate C


Philip Mosier PhD Assistant Professor in the School of Pharmacy Administration department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Models, Molecular
Molecular Structure
Optical Imaging
Receptors, sigma
Tumor Cells, Cultured