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Review
. 2025 Mar 7;8(4):951-977.
doi: 10.1021/acsptsci.4c00711. eCollection 2025 Apr 11.

Recent Advances in the Development of Sigma Receptor (Radio)Ligands and Their Application in Tumors

Tao Wang  1   2   3 , Na Sun  1 , Yanxi Ma  1 , Song Zhang  1
Affiliations
Review

Recent Advances in the Development of Sigma Receptor (Radio)Ligands and Their Application in Tumors

Tao Wang et al. ACS Pharmacol Transl Sci. .

Abstract

Cancer ranks among the top triumvirate leading causes of human deaths worldwide. The pathological mechanisms are notably intricate, demonstrating proliferative and metastatic capabilities, which complicate therapeutic interventions. The sigma-1 receptor (σ1R) plays a crucial role in tumor survival and migration, while the sigma-2 receptor (σ2R) is intimately associated with tumor proliferation. This review encapsulated the investigation concerning σ1R and σ2R in neoplasms and rigorously summarized the ligands and radio-ligands development and their tumor applications, such as antitumor cell proliferation and PET/SPECT imaging in tumors. A comprehensive classification discussion was undertaken regarding the chemical structures and emphasized the possibility of dual/multitargeted ligands. Ultimately, we discussed the effects of chiral structures and the pharmacological characteristics of ligands on affinity and pharmacokinetic features in vivo, particularly concerning radiopharmaceuticals. This review functions as a beneficial resource, fostering ligand deployment and stimulating the generation of innovative ideas for developing innovative radiopharmaceuticals.

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Conflict of interest statement

The authors declare no competing financial interest.

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