Next Article in Journal
Novel Bacterial Production of Two Different Bioactive Forms of Human Stem-Cell Factor
Next Article in Special Issue
Neuroprotective Effects of Sigma 1 Receptor Ligands on Motoneuron Death after Spinal Root Injury in Mice
Previous Article in Journal
Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives
Previous Article in Special Issue
Propellanes as Rigid Scaffolds for the Stereodefined Attachment of σ-Pharmacophoric Structural Elements to Achieve σ Affinity
Review

Multi-Target Directed Ligands (MTDLs) Binding the σ1 Receptor as Promising Therapeutics: State of the Art and Perspectives

Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari ALDO MORO, Via Orabona 4, 70125 Bari, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Botond Penke
Int. J. Mol. Sci. 2021, 22(12), 6359; https://doi.org/10.3390/ijms22126359
Received: 13 May 2021 / Revised: 31 May 2021 / Accepted: 10 June 2021 / Published: 14 June 2021
The sigma-1 (σ1) receptor is a ‘pluripotent chaperone’ protein mainly expressed at the mitochondria–endoplasmic reticulum membrane interfaces where it interacts with several client proteins. This feature renders the σ1 receptor an ideal target for the development of multifunctional ligands, whose benefits are now recognized because several pathologies are multifactorial. Indeed, the current therapeutic regimens are based on the administration of different classes of drugs in order to counteract the diverse unbalanced physiological pathways associated with the pathology. Thus, the multi-targeted directed ligand (MTDL) approach, with one molecule that exerts poly-pharmacological actions, may be a winning strategy that overcomes the pharmacokinetic issues linked to the administration of diverse drugs. This review aims to point out the progress in the development of MTDLs directed toward σ1 receptors for the treatment of central nervous system (CNS) and cancer diseases, with a focus on the perspectives that are proper for this strategy. The evidence that some drugs in clinical use unintentionally bind the σ1 protein (as off-target) provides a proof of concept of the potential of this strategy, and it strongly supports the promise that the σ1 receptor holds as a target to be hit in the context of MTDLs for the therapy of multifactorial pathologies. View Full-Text
Keywords: sigma receptors; sigma-1 receptor; multi-target directed ligands (MTDLs); sigma-1 ligands; polypharmacology sigma receptors; sigma-1 receptor; multi-target directed ligands (MTDLs); sigma-1 ligands; polypharmacology
Show Figures

Figure 1

MDPI and ACS Style

Abatematteo, F.S.; Niso, M.; Contino, M.; Leopoldo, M.; Abate, C. Multi-Target Directed Ligands (MTDLs) Binding the σ1 Receptor as Promising Therapeutics: State of the Art and Perspectives. Int. J. Mol. Sci. 2021, 22, 6359. https://doi.org/10.3390/ijms22126359

AMA Style

Abatematteo FS, Niso M, Contino M, Leopoldo M, Abate C. Multi-Target Directed Ligands (MTDLs) Binding the σ1 Receptor as Promising Therapeutics: State of the Art and Perspectives. International Journal of Molecular Sciences. 2021; 22(12):6359. https://doi.org/10.3390/ijms22126359

Chicago/Turabian Style

Abatematteo, Francesca S., Mauro Niso, Marialessandra Contino, Marcello Leopoldo, and Carmen Abate. 2021. "Multi-Target Directed Ligands (MTDLs) Binding the σ1 Receptor as Promising Therapeutics: State of the Art and Perspectives" International Journal of Molecular Sciences 22, no. 12: 6359. https://doi.org/10.3390/ijms22126359

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop