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Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
REVIEW

Recent Advances in the Development of Sigma-1 Receptor Ligands

Madhura Manohar A , Samuel D. Banister A , Corinne Beinat A , James O'Brien-Brown A and Michael Kassiou A B C
+ Author Affiliations
- Author Affiliations

A School of Chemistry, The University of Sydney, NSW 2006, Australia.

B Faculty of Health Science, The University of Sydney, NSW 2006, Australia.

C Corresponding author. Email: michael.kassiou@sydney.edu.au




Madhura Manohar is a Ph.D. candidate at the University of Sydney, working with Professor Michael Kassiou on the development of novel sigma-1 receptor ligands. She completed her undergraduate studies at the University of Western Sydney, obtaining her B.Sc. (advanced) in 2008 and M.Sc. in 2010. Her research interests include broad areas of synthetic and medicinal chemistry, in particular drug design pertaining to anti-cancer and central nervous system therapeutics.



Samuel D. Banister is a Postdoctoral Fellow in the Molecular Imaging Program at Stanford (MIPS) within the Stanford University School of Medicine. He completed his undergraduate studies at the University of Sydney, obtaining a B.Sc. (Hons) in 2006. Following the conferral of a Ph.D. in Medicinal Chemistry from the University of Sydney in 2011, he worked as a Postdoctoral Research Associate with Professor Michael Kassiou for several years before taking up his current position. His research interests include the synthesis and pharmacological evaluation of small molecules with therapeutic activity in disorders of the central nervous system, as well as the development of novel strategies for cancer imaging, with a particular focus on glioblastoma multiforme and tumour hypoxia.



Corinne Beinat is a Postdoctoral Research Associate in the School of Chemistry at the University of Sydney. She completed her undergraduate studies at the University of Sydney and obtained a B.Sc. (Hons) in 2010. She then obtained her Ph.D. from the University of Sydney in 2014. Her research interests include the synthesis of biologically active molecules with specific emphasis on application to diseases of the central nervous system.



James O'Brien-Brown is an Honours student at the University of Sydney, he is currently developing central nervous system-active compounds with Professor Michael Kassiou. His research interests include synthetic organic and medicinal chemistry, particularly the discovery of centrally active drugs for the treatment of neurodegenerative diseases.



Michael Kassiou is Professor of Medicinal Chemistry at the University of Sydney. He received his Ph.D. in Chemistry from the University of New South Wales in 1992. He has been a Postdoctoral Fellow at Johns Hopkins University and a Fogarty Fellow at the National Institute of Drug Abuse, National Institutes of Health in the USA. His research interests include medicinal chemistry, heterocyclic chemistry, drug discovery, and structure-activity relationships of molecules with activity in the central nervous system. He serves on several journal editorial boards focussing on medicinal chemistry, pharmaceutical design and drug discovery.

Australian Journal of Chemistry 68(4) 600-609 https://doi.org/10.1071/CH14590
Submitted: 26 September 2014  Accepted: 17 October 2014   Published: 6 February 2015

Abstract

The existence of two distinct sigma (σ) receptor subtypes was established in the early 1990s. Sigma-1 and sigma-2 receptors (S1Rs and S2Rs, respectively) were shown to possess distinct molecular size, anatomical distribution, and ligand discrimination. S2R is overexpressed in numerous human cancers, and has therapeutic potential for the imaging and treatment of certain tumours. In contrast, S1R is more broadly involved in a wide variety of central nervous system (CNS) diseases including motor disorders, memory deficits, depression, schizophrenia, anxiety, pain, drug addiction, and many more. Since the human S1R was cloned in 1996, numerous high affinity ligands with excellent selectivity for S1R have been developed. This review focuses on recent developments in the generation of structurally diverse S1R-selective ligands and novel therapeutic candidates targeting S1Rs.


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