Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT5TPI6)

• DTT Name: Opioid receptor sigma 1 (OPRS1)
• Synonyms: hSigmaR1; Sigma1R; Sigma1-receptor; Sigma non-opioid intracellular receptor 1; Sigma 1-type opioid receptor; SRBP; SR31747-binding protein; SR31747 binding protein 1; SR-BP; SIG-1R; Opioid receptor, sigma 1, isoform 1; OPRS1 protein; Aging-associated gene 8 protein; AAG8
• Gene Name: SIGMAR1
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: SGMR1_HUMAN
• TTD ID: T46360
• Sequence:
  MQWAVGRRWAWAALLLAVAAVLTQVVWLWLGTQSFVFQREEIAQLARQYAGLDHELAFSR
  LIVELRRLHPGHVLPDEELQWVFVNAGGWMGAMCLLHASLSEYVLLFGTALGSRGHSGRY
  WAEISDTIISGTFHQWREGTTKSEVFYPGETVVHGPGEATAVEWGPNTWMVEYGRGVIPS
  TLAFALADTVFSTQDFLTLFYTLRSYARGLRLELTTYLFGQDP
• Function: Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration. Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria. Plays a role in protecting cells against oxidative stress-induced cell death via its interaction with RNF112. Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane.
• KEGG Pathway:
  Amyotrophic lateral sclerosis (hsa05014)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway: Potential therapeutics for SARS (R-HSA-9679191)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dextromethorphan	DMUDJZM	Allergic rhinitis	CA08.0	Approved	[1]
Dextromethorphan Polistirex	DMEHCY5	Dry cough	MD12	Approved	[2]

10 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ADX N05	DMLBYRA	Mood disorder	6A60-6E23	Phase 3	[3]
AVP-786	DMV1SOR	Alzheimer disease	8A20	Phase 3	[4]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[5]
Igmesine	DMH97XA	Major depressive disorder	6A70.3	Phase 2	[6]
OPC-14523	DMB1WF3	Bulimia nervosa	6B81	Phase 2	[7]
ANAVEX 2-73	DM67OU4	Alzheimer disease	8A20	Phase 1	[8]
ANAVEX 3-71	DM31634	Frontotemporal dementia	6D83	Phase 1	[9]
SA-5845	DM6XZRL	Central nervous system disease	8A04-8D87	Phase 1	[10]
SSR-125047	DMSUFW6	Schizophrenia	6A20	Phase 1	[11]
SSR-125329A	DMG6NI8	Immune System disease	4A01-4B41	Phase 1	[12]

27 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,2,4-triazole derivative 3	DMU9XMV	N. A.	N. A.	Patented	[13]
1,2,4-triazole derivative 4	DMHBJFN	N. A.	N. A.	Patented	[13]
Aryl alkanolamine derivative 1	DM417XY	N. A.	N. A.	Patented	[13]
Aryl alkanolamine derivative 2	DMUP0WH	N. A.	N. A.	Patented	[13]
Benzamide derivative 10	DM9PKU2	N. A.	N. A.	Patented	[14]
Benzamide derivative 11	DM4V3Y5	N. A.	N. A.	Patented	[14]
Benzamide derivative 7	DM7UEJT	N. A.	N. A.	Patented	[14]
Benzamide derivative 8	DMAIJHC	N. A.	N. A.	Patented	[14]
Benzamide derivative 9	DMVFSJZ	N. A.	N. A.	Patented	[14]
Isoindoline derivative 1	DMD19QC	N. A.	N. A.	Patented	[14]
Isoindoline derivative 2	DMTE0S3	N. A.	N. A.	Patented	[14]
Isoindoline derivative 3	DM2MYL9	N. A.	N. A.	Patented	[14]
Isoindoline derivative 4	DMP1NKI	N. A.	N. A.	Patented	[14]
Isoindoline derivative 5	DMIUTQW	N. A.	N. A.	Patented	[14]
Phenylpropylamine derivative 1	DMVCKZT	N. A.	N. A.	Patented	[13]
Phenylpropylamine derivative 2	DMTDIA6	N. A.	N. A.	Patented	[13]
Phenylpropylamine derivative 3	DMH3FUR	N. A.	N. A.	Patented	[13]
Phenylpropylamine derivative 4	DM0R653	N. A.	N. A.	Patented	[13]
Phenylpropylamine derivative 5	DMU0S2W	N. A.	N. A.	Patented	[13]
Piperazine derivative 7	DM9Y4ZV	N. A.	N. A.	Patented	[13]
Piperidine derivative 4	DM6C5DR	N. A.	N. A.	Patented	[13]
Piperidine derivative 5	DMQ0VK4	N. A.	N. A.	Patented	[13]
Piperidine derivative 6	DM0GCTY	N. A.	N. A.	Patented	[13]
PMID28051882-Compound-XIV	DM1RN89	N. A.	N. A.	Patented	[13]
PMID30185082-Compound-57	DMNDF1Z	N. A.	N. A.	Patented	[14]
PMID30185082-Compound-64	DMKD470	N. A.	N. A.	Patented	[14]
Pyrazole derivative 86	DMW3PJV	N. A.	N. A.	Patented	[13]

20 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BMS-181100	DM0HR5W	Psychotic disorder	6A20-6A25	Discontinued in Phase 3	[15]
KB-5492	DM7IP8U	Peptic ulcer	DA61	Discontinued in Phase 2	[16]
OxycoDex	DMHFOIX	Pain	MG30-MG3Z	Discontinued in Phase 2	[4]
Panamesine	DM6TPCJ	Psychotic disorder	6A20-6A25	Discontinued in Phase 2	[17]
DUP-734	DMI5EPB	Psychotic disorder	6A20-6A25	Discontinued in Phase 1	[18]
Gevotroline	DM520D8	Psychotic disorder	6A20-6A25	Discontinued in Phase 1	[19]
AH-9700	DMXY5AV	Pollakiuria	MF50.1	Terminated	[21]
CNS-1307	DM03LZB	Schizophrenia	6A20	Terminated	[4]
E-5842	DMV0QI1	Schizophrenia	6A20	Terminated	[11]
E-6276	DMTEY8W	Schizophrenia	6A20	Terminated	[11]
FH-510	DMJ35RC	Psychotic disorder	6A20-6A25	Terminated	[22]
HydrocoDex	DM4HA9C	Pain	MG30-MG3Z	Terminated	[4]
LU-29252	DMDHLUC	Anxiety disorder	6B00-6B0Z	Terminated	[23]
MS-377	DMXERCA	Schizophrenia	6A20	Terminated	[11]
NE-033	DMEH50J	Psychotic disorder	6A20-6A25	Terminated	[24]
NE-100	DMP4J7T	Schizophrenia	6A20	Terminated	[11]
NPC-16377	DM35RTJ	Psychotic disorder	6A20-6A25	Terminated	[25]
PRE-084	DMDIYFH	Aging skin	EE40	Terminated	[26]
Rimcazole	DMKDS1C	Schizophrenia	6A20	Terminated	[11]
SR-31742A	DM7ZOLE	Schizophrenia	6A20	Terminated	[11]

3 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ANAVEX 1-41	DM1MQON	Alzheimer disease	8A20	Preclinical	[8]
ANAVEX 1007	DM2U16Z	Melanoma	2C30	Preclinical	[8]
Cutamesine	DMB1ET0	Major depressive disorder	6A70.3	Preclinical	[20]

12 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+)-SK&F10047	DM1QPA4	Discovery agent	N.A.	Investigative	[27]
(RS)-PPCC	DMA8DEG	Discovery agent	N.A.	Investigative	[28]
1,3-ditolylguanidine	DM04KS1	Discovery agent	N.A.	Investigative	[29]
2-(1H-indol-3-yl)-N,N-dimethylethanamine	DMR9Q4Y	Discovery agent	N.A.	Investigative	[30]
BD-1047	DMFIDA0	Discovery agent	N.A.	Investigative	[31]
C-10068	DMNV1ST	Brain injury	NA07.Z	Investigative	[4]
CM-156	DM7TX3D	Drug abuse	6C4G.1Z	Investigative	[4]
CNS-1169	DMTEGNB	Schizophrenia	6A20	Investigative	[4]
Dimemorfan	DM2Q3CL	Discovery agent	N.A.	Investigative	[32]
MC-113	DMPTNUQ	Central nervous system disease	8A04-8D87	Investigative	[4]
MC-116	DMQC9UB	Central nervous system disease	8A04-8D87	Investigative	[4]
[3H]pentazocine	DMF4TWE	Discovery agent	N.A.	Investigative	[27]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alzheimer's disease	8A00.0	Entorhinal cortex	2.77E-06	-0.12	-0.62
Major depressive disorder	6A20	Pre-frontal cortex	4.34E-01	0.03	0.26
Prostate cancer	2C82	Prostate	9.08E-03	0.31	0.6
Melanoma	2C82	Skin	7.53E-01	-3.56E-03	-0.01
Schizophrenia	6A20	Pre-frontal cortex	7.77E-01	-0.02	-0.07
Schizophrenia	6A20	Superior temporal cortex	1.88E-01	-0.01	-0.17
Breast cancer	2C82	Breast tissue	1.60E-20	0.27	0.63

References

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