Target Information

Target General Infomation
Target ID
T46360
Former ID
TTDS00129
Target Name
Sigma(1)-type opioid receptor
Gene Name
SIGMAR1
Synonyms
OPRS1 protein; Opioid receptor, sigma 1, isoform 1; SR31747 binding protein 1; SIGMAR1
Target Type
Successful
Disease Anxiety disorder [ICD9: 300, 311; ICD10: F32, F40-F42]
Aging skin [ICD10: L00-L99]
Alzheimer disease [ICD9: 331; ICD10: G30]
Breast cancer [ICD9: 174, 175; ICD10: C50]
Bulimia nervosa; Severe mood disorders [ICD9: 296, 307.51; ICD10: F30-F39, F50.2]
Brain injury [ICD10: S09.90]
Central nervous system disease [ICD10: G00-G99]
Cough; Pain [ICD9: 338, 786.2,780; ICD10: R05, R52, G89]
Drug abuse [ICD9: 303-304; ICD10: F10-F19]
Dry cough [ICD10: R05]
Excessive daytime sleepiness [ICD9: 291.82, 292.85, 307.43-307.44, 327.1, 780.53-780.54; ICD10: F51.1, G47.1]
Female sexual dysfunction [ICD9: 302.7; ICD10: F52]
Immuno-modulator [ICD9: 135, 691.8, 692.9, 710-719, 714; ICD10: D86, L20, L20-L30, M00-M25, M05-M06]
Melanoma; Prostate cancer; Pancreatic cancer [ICD9: 140-229, 157, 172, 185; ICD10: C25, C43, C61]
Mood disorder [ICD10: F30-F39]
Major depressive disorder [ICD9: 296.2, 296.3, 710.0; ICD10: F32, F33, M32]
Psychotic disorders [ICD9: 290-299; ICD10: F20-F29]
Peptic ulcer [ICD9: 531-534; ICD10: K25-K27]
Pollakiuria [ICD10: R35]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
Schizophrenia [ICD9: 295; ICD10: F20]
BioChemical Class
Transmembrane protein
Target Validation
T46360
UniProt ID
Q99720
Sequence
MQWAVGRRWAWAALLLAVAAVLTQVVWLWLGTQSFVFQREEIAQLARQYAGLDHELAFSR
LIVELRRLHPGHVLPDEELQWVFVNAGGWMGAMCLLHASLSEYVLLFGTALGSRGHSGRY
WAEISDTIISGTFHQWREGTTKSEVFYPGETVVHGPGEATAVEWGPNTWMVEYGRGVIPS
TLAFALADTVFSTQDFLTLFYTLRSYARGLRLELTTYLFGQDP
Drugs and Mode of Action
Drug(s) Dextromethorphan Drug Info Approved Cough; Pain [1], [2]
Dextromethorphan Polistirex Drug Info Approved Dry cough [3]
ADX N05 Drug Info Phase 3 Mood disorder [4]
CM-2395 Drug Info Phase 3 Schizophrenia [5]
ADX N05 Drug Info Phase 2 Excessive daytime sleepiness [4]
ANAVEX 2-73 Drug Info Phase 2 Breast cancer [6], [7]
Igmesine Drug Info Phase 2 Major depressive disorder [8]
OPC-14523 Drug Info Phase 2 Bulimia nervosa; Severe mood disorders [9]
ANAVEX 2-73 Drug Info Phase 1 Alzheimer disease [10]
AVP-786 Drug Info Phase 1 Pain [11], [12]
OPC-14523 Drug Info Phase 1 Female sexual dysfunction [9]
SA-5845 Drug Info Phase 1 Central nervous system disease [11], [13], [12]
SSR-125047 Drug Info Phase 1 Schizophrenia [14]
SSR-125329A Drug Info Phase 1 Immuno-modulator [15]
ANAVEX 1-41 Drug Info Preclinical Alzheimer disease [10]
ANAVEX 1007 Drug Info Preclinical Melanoma; Prostate cancer; Pancreatic cancer [10]
Cutamesine Drug Info Preclinical Major depressive disorder [16]
SA-5845 Drug Info Preclinical Psychotic disorders [17]
BMS-181100 Drug Info Discontinued in Phase 3 Psychotic disorders [18], [19]
KB-5492 Drug Info Discontinued in Phase 2 Peptic ulcer [20]
OxycoDex Drug Info Discontinued in Phase 2 Pain [21]
Panamesine Drug Info Discontinued in Phase 2 Psychotic disorders [22]
DUP-734 Drug Info Discontinued in Phase 1 Psychotic disorders [23]
Gevotroline Drug Info Discontinued in Phase 1 Psychotic disorders [24]
AH-9700 Drug Info Terminated Pollakiuria [25]
CNS-1307 Drug Info Terminated Schizophrenia [26]
E-5842 Drug Info Terminated Schizophrenia [14]
E-6276 Drug Info Terminated Schizophrenia [14]
FH-510 Drug Info Terminated Psychotic disorders [27]
HydrocoDex Drug Info Terminated Pain [11], [12]
LU-29252 Drug Info Terminated Anxiety disorder [28]
MS-377 Drug Info Terminated Schizophrenia [14]
NE-033 Drug Info Terminated Psychotic disorders [29]
NE-100 Drug Info Terminated Schizophrenia [14], [30]
NPC-16377 Drug Info Terminated Psychotic disorders [31]
PRE-084 Drug Info Terminated Aging skin [32], [33]
Rimcazole Drug Info Terminated Schizophrenia [14]
SR-31742A Drug Info Terminated Schizophrenia [14]
Agonist (+)-SK&F10047 Drug Info [34]
(RS)-PPCC Drug Info [35]
1,3-ditolylguanidine Drug Info [36]
ANAVEX 1-41 Drug Info [10]
ANAVEX 1007 Drug Info [10]
ANAVEX 2-73 Drug Info [10]
C-10068 Drug Info [11], [12]
CM-2395 Drug Info [37]
Cutamesine Drug Info [11], [12], [38]
Dextromethorphan Drug Info [39]
Dimemorfan Drug Info [40]
Igmesine Drug Info [41], [42], [43]
MC-113 Drug Info [11], [12]
MC-116 Drug Info [11], [12]
[3H]pentazocine Drug Info [34]
Modulator ADX N05 Drug Info [44]
AH-9700 Drug Info [45]
AVP-786 Drug Info [11], [12]
BMS-181100 Drug Info
CNS-1169 Drug Info [11], [12]
CNS-1307 Drug Info [11], [12]
Dextromethorphan Polistirex Drug Info [46]
DUP-734 Drug Info
FH-510 Drug Info [11], [12], [47]
Gevotroline Drug Info
HydrocoDex Drug Info [11], [12]
LU-29252 Drug Info [48], [11], [12]
NE-033 Drug Info [11], [12], [49]
NPC-16377 Drug Info [11], [12], [50]
OPC-14523 Drug Info [51]
OxycoDex Drug Info [11], [12]
PRE-084 Drug Info [11], [52], [12]
Antagonist BD-1047 Drug Info [53]
CM-156 Drug Info [11], [12]
KB-5492 Drug Info [11], [12], [54]
MS-377 Drug Info [14]
NE-100 Drug Info [14]
Rimcazole Drug Info [14]
Inhibitor Dimethyltryptamine Drug Info [55]
DITOLYLGUANIDINE Drug Info [56]
Binder E-5842 Drug Info [14]
E-6276 Drug Info [14]
Panamesine Drug Info [57], [11], [12]
SA-5845 Drug Info [11], [13], [12]
SR-31742A Drug Info [14]
SSR-125047 Drug Info [14]
SSR-125329A Drug Info [15], [11], [12]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
WikiPathways miR-targeted genes in squamous cell - TarBase
miR-targeted genes in lymphocytes - TarBase
References
REF 1Molecular insights and therapeutic targets in amyotrophic lateral sclerosis. CNS Neurol Disord Drug Targets. 2008 Feb;7(1):11-9.
REF 2(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6953).
REF 3Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 4Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030225)
REF 5Pharmaceutical Research Companies Are Developing More Than 300 Medicines to Treat Mental Illnesses. Pharmaceutical Research and Manufacturers of America report.2010.
REF 6Anti-amnesic and neuroprotective potentials of the mixed muscarinic receptor/sigma 1 (?1) ligand ANAVEX2-73, a novel aminotetrahydrofuran derivative. J Psychopharmacol. 2011 Aug;25(8):1101-17.
REF 7Blockade of Tau hyperphosphorylation and Abeta?????? generation by the aminotetrahydrofuran derivative ANAVEX2-73, a mixed muscarinic and ???receptor agonist, in a nontransgenic mouse model of Alzheimer's disease. Neuropsychopharmacology. 2013 Aug;38(9):1706-23.
REF 8Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001429)
REF 9Designing drugs for the treatment of female sexual dysfunction. Drug Discov Today. 2007 Sep;12(17-18):757-66. Epub 2007 Aug 27.
REF 102011 Pipeline of Anavex.
REF 11Dextromethorphan antagonizes the acute depletion of brain serotonin by p-chloroamphetamine and H75/12 in rats. Brain Res. 1992 Oct 30;594(2):323-6.
REF 12Antitussives and substance abuse. Subst Abuse Rehabil. 2013 Nov 6;4:75-82.
REF 13Tumor imaging with 2 sigma-receptor ligands, 18F-FE-SA5845 and 11C-SA4503: a feasibility study. J Nucl Med. 2004 Nov;45(11):1939-45.
REF 14The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. Epub 2007 Jul 31.
REF 15SSR125329A, a high affinity sigma receptor ligand with potent anti-inflammatory properties. Eur J Pharmacol. 2002 Dec 5;456(1-3):123-31.
REF 16Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007486)
REF 17Preclinical evaluation of [11C]SA4503: radiation dosimetry, in vivo selectivity and PET imaging of sigma1 receptors in the cat brain. Ann Nucl Med. 2000 Aug;14(4):285-92.
REF 18(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8).
REF 19Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000679)
REF 20Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001141)
REF 21Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017613)
REF 22Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001428)
REF 23Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001777)
REF 24Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001398)
REF 25Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010610)
REF 26Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003010)
REF 27Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002069)
REF 28Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003571)
REF 29Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004064)
REF 30(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6679).
REF 31Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001997)
REF 32Self-administration of cocaine induces dopamine-independent self-administration of sigma agonists. Neuropsychopharmacology. 2013 Mar;38(4):605-15.
REF 33(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6678).
REF 34(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2552).
REF 35Novel sigma receptor ligands: synthesis and biological profile. J Med Chem. 2007 Mar 8;50(5):951-61. Epub 2007 Feb 13.
REF 36Sigma1 and sigma2 receptor binding affinity and selectivity of SA4503 and fluoroethyl SA4503. Synapse. 2006 May;59(6):350-8.
REF 37Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
REF 38Effect of SA4503, a novel sigma1 receptor agonist, against glutamate neurotoxicity in cultured rat retinal neurons. Eur J Pharmacol. 1998 Jan 19;342(1):105-11.
REF 39Dextromethorphan/quinidine: AVP 923, dextromethorphan/cytochrome P450-2D6 inhibitor, quinidine/dextromethorphan. Drugs R D. 2005;6(3):174-7.
REF 40Dimemorfan protects rats against ischemic stroke through activation of sigma-1 receptor-mediated mechanisms by decreasing glutamate accumulation. J Neurochem. 2008 Jan;104(2):558-72.
REF 41Strain differences in sigma(1) receptor-mediated behaviours are related to neurosteroid levels. Eur J Neurosci. 2002 May;15(9):1523-34.
REF 42Sigma-1 receptor ligands: potential in the treatment of neuropsychiatric disorders. CNS Drugs. 2004;18(5):269-84.
REF 43Antiamnesic and neuroprotective effects of donepezil against learning impairments induced in mice by exposure to carbon monoxide gas. J Pharmacol Exp Ther. 2006 Jun;317(3):1307-19. Epub 2006 Mar 21.
REF 44Clinical pipeline report, company report or official report of SK BioPhamaceuticals.
REF 45Pharmacological actions of AH-9700 on micturition reflex in anesthetized rats. Eur J Pharmacol. 2001 Jan 26;412(2):171-9.
REF 46Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
REF 47FH-510, a potent and selective ligand for rat brain sigma recognition sites. Eur J Pharmacol. 1993 Jul 6;238(1):89-92.
REF 48Involvement of sigma receptors in the modulation of the glutamatergic/NMDA neurotransmission in the dopaminergic systems. Eur J Pharmacol. 1999 Mar 5;368(2-3):183-96.
REF 49Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004064)
REF 50Effects of the selective sigma receptor ligand, 6-[6-(4-hydroxypiperidinyl)hexyloxy]-3-methylflavone (NPC 16377), on behavioral and toxic effects of cocaine. J Pharmacol Exp Ther. 1993 Aug;266(2):473-82.
REF 51Antidepressant-like responses to the combined sigma and 5-HT1A receptor agonist OPC-14523. Neuropharmacology. 2001 Dec;41(8):976-88.
REF 52Antidepressant-like effect of PRE-084, a selective sigma1 receptor agonist, in Albino Swiss and C57BL/6J mice. Pharmacol Rep. 2009 Nov-Dec;61(6):1179-83.
REF 53Characterization of two novel sigma receptor ligands: antidystonic effects in rats suggest sigma receptor antagonism. Eur J Pharmacol. 1995 Jul 14;280(3):301-10.
REF 54Sigma receptor-mediated effects of a new antiulcer agent, KB-5492, on experimental gastric mucosal lesions and gastric alkaline secretion in rats. J Pharmacol Exp Ther. 1994 May;269(2):799-805.
REF 55Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects. Arch Gen Psychiatry. 1994 Feb;51(2):85-97.
REF 56J Med Chem. 1994 Jun 10;37(12):1737-9.Synthesis and characterization of [125I]-N-(N-benzylpiperidin-4-yl)-4- iodobenzamide, a new sigma receptor radiopharmaceutical: high-affinity binding to MCF-7 breast tumor cells.
REF 57Efficacy and safety of the sigma receptor ligand EMD 57445 (panamesine) in patients with schizophrenia: an open clinical trial. Pharmacopsychiatry. 1999 Mar;32(2):68-72.

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