TY - JOUR
T1 - Small Molecules Selectively Targeting Sigma-1 Receptor for the Treatment of Neurological Diseases
AU - Ye, Na
AU - Qin, Wangzhi
AU - Tian, Sheng
AU - Xu, Qingfeng
AU - Wold, Eric A.
AU - Zhou, Jia
AU - Zhen, Xue Chu
N1 - Publisher Copyright:
©
PY - 2020/12/24
Y1 - 2020/12/24
N2 - The sigma-1 (σ1) receptor, an enigmatic protein originally classified as an opioid receptor subtype, is now understood to possess unique structural and functional features of its own and play critical roles to widely impact signaling transduction by interacting with receptors, ion channels, lipids, and kinases. The σ1 receptor is implicated in modulating learning, memory, emotion, sensory systems, neuronal development, and cognition and accordingly is now an actively pursued drug target for various neurological and neuropsychiatric disorders. Evaluation of the five selective σ1 receptor drug candidates (pridopidine, ANAVEX2-73, SA4503, S1RA, and T-817MA) that have entered clinical trials has shown that reaching clinical approval remains an evasive and important goal. This review provides up-to-date information on the selective targeting of σ1 receptors, including their history, function, reported crystal structures, and roles in neurological diseases, as well as a useful collation of new chemical entities as σ1 selective orthosteric ligands or allosteric modulators.
AB - The sigma-1 (σ1) receptor, an enigmatic protein originally classified as an opioid receptor subtype, is now understood to possess unique structural and functional features of its own and play critical roles to widely impact signaling transduction by interacting with receptors, ion channels, lipids, and kinases. The σ1 receptor is implicated in modulating learning, memory, emotion, sensory systems, neuronal development, and cognition and accordingly is now an actively pursued drug target for various neurological and neuropsychiatric disorders. Evaluation of the five selective σ1 receptor drug candidates (pridopidine, ANAVEX2-73, SA4503, S1RA, and T-817MA) that have entered clinical trials has shown that reaching clinical approval remains an evasive and important goal. This review provides up-to-date information on the selective targeting of σ1 receptors, including their history, function, reported crystal structures, and roles in neurological diseases, as well as a useful collation of new chemical entities as σ1 selective orthosteric ligands or allosteric modulators.
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U2 - 10.1021/acs.jmedchem.0c01192
DO - 10.1021/acs.jmedchem.0c01192
M3 - Review article
C2 - 33111525
AN - SCOPUS:85095804248
SN - 0022-2623
VL - 63
SP - 15187
EP - 15217
JO - Journal of medicinal chemistry
JF - Journal of medicinal chemistry
IS - 24
ER -