Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTEX6LM)

• DTT Name: GABA(A) receptor gamma-3 (GABRG3)
• Synonyms: GABRG3
• Gene Name: GABRG3
• DTT Type: Successful target; [1]
• Related Disease:
  Anxiety disorder [ICD-11: 6B00-6B0Z]
  Corneal disease [ICD-11: 9A76-9A78]
  Depression [ICD-11: 6A70-6A7Z]
  Epilepsy/seizure [ICD-11: 8A61-8A6Z]
  Insomnia [ICD-11: 7A00-7A0Z]
  Intentional self-harm [ICD-11: PC91]
  Labour/delivery anaesthesia complication [ICD-11: JB0C]
  Mental/behavioural/neurodevelopmental disorder [ICD-11: 6E20-6E8Z]
  Mood/affect symptom [ICD-11: MB24]
• BioChemical Class: Ligand-gated ion channel
• UniProt ID: GBRG3_HUMAN
• TTD ID: T28722
• Sequence:
  MAPKLLLLLCLFSGLHARSRKVEEDEYEDSSSNQKWVLAPKSQDTDVTLILNKLLREYDK
  KLRPDIGIKPTVIDVDIYVNSIGPVSSINMEYQIDIFFAQTWTDSRLRFNSTMKILTLNS
  NMVGLIWIPDTIFRNSKTAEAHWITTPNQLLRIWNDGKILYTLRLTINAECQLQLHNFPM
  DEHSCPLIFSSYGYPKEEMIYRWRKNSVEAADQKSWRLYQFDFMGLRNTTEIVTTSAGDY
  VVMTIYFELSRRMGYFTIQTYIPCILTVVLSWVSFWIKKDATPARTALGITTVLTMTTLS
  TIARKSLPRVSYVTAMDLFVTVCFLFVFAALMEYATLNYYSSCRKPTTTKKTTSLLHPDS
  SRWIPERISLQAPSNYSLLDMRPPPTAMITLNNSVYWQEFEDTCVYECLDGKDCQSFFCC
  YEECKSGSWRKGRIHIDILELDSYSRVFFPTSFLLFNLVYWVGYLYL
• Function: Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functionsas receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand- gated chloride channel.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Retrograde endocannabinoid signaling (hsa04723)
  GABAergic synapse (hsa04727)
  Morphine addiction (hsa05032)
  Nicotine addiction (hsa05033)
• Reactome Pathway:
  GABA A receptor activation (R-HSA-977441)
  Ligand-gated ion channel transport (R-HSA-975298)

Molecular Interaction Atlas (MIA) of This DTT

12 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Allopregnanolone	DMNLHAC	Depression	6A70-6A7Z	Approved	[2], [3]
Bentazepam	DMRVBWU	Anxiety disorder	6B00-6B0Z	Approved	[1], [4]
Clobazam - Lundbeck	DMW1OQ0	Anxiety disorder	6B00-6B0Z	Approved	[5]
Etomidate	DMZI3WO	Anaesthesia	9A78.6	Approved	[5]
Flumazenil	DMPCG2L	Benzodiazepine overdose	PC91	Approved	[6]
Mebutamate	DM0KYI4	Anxiety disorder	6B00-6B0Z	Approved	[5]
Metharbital	DM5A38V	Epilepsy	8A60-8A68	Approved	[5]
Remimazolam	DMLVSYX	Procedural sedation	JB0C.3	Approved	[7]
Stiripentol	DMMSDOY	Dravet syndrome	8A61.11	Approved	[8], [4]
Talbutal	DM214Q8	Irritability	MB24	Approved	[5]
Thiamylal	DMHDF7B	Anaesthesia	9A78.6	Approved	[5]
Zolpidem	DMWOSKJ	Insomnia	7A00-7A0Z	Approved	[6]

12 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Arbaclofen placarbil	DMO628K	Fragile X syndrome	LD55	Phase 3	[2]
Clomethiazole	DMSPN58	Stroke	8B20	Phase 3	[9]
Ganaxolone	DMXJMKF	Complex partial seizure	8A68.0	Phase 3	[2], [3], [10]
SAGE-217	DMGR98T	Postpartum depression	6E20.0	Phase 3	[2], [3]
Pagoclone	DMHWY2G	Anxiety disorder	6B00-6B0Z	Phase 2/3	[11]
Etazolate	DMOCID7	Neurodegenerative disorder	8A20-8A23	Phase 2	[12]
EVT-201	DMQGBM1	Insomnia	7A00-7A0Z	Phase 2	[6]
SARIPIDEM	DM5R89X	Anxiety disorder	6B00-6B0Z	Phase 2	[13]
T-2007	DMF9Z2T	Epilepsy	8A60-8A68	Phase 2	[6]
AZD-3043	DMXFYN0	Anaesthesia	9A78.6	Phase 1	[14]
NSD-788	DM5QHID	Anxiety disorder	6B00-6B0Z	Phase 1	[6]
Org-25435	DMBG534	Epilepsy	8A60-8A68	Phase 1	[15]

21 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Suriclone	DMC14HL	Anxiety disorder	6B00-6B0Z	Discontinued in Preregistration	[16]
Ocinaplon	DMQN3JX	Generalized anxiety disorder	6B00	Discontinued in Phase 3	[17]
Pazinaclone	DM1FST8	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 3	[18]
Y-23684	DM3EZ68	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 3	[19]
LORECLEZOLE	DMCZI62	Epileptic seizures	8A61-8A6Z	Discontinued in Phase 2	[20]
NGD 91-3	DMDAUCR	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 2	[21]
RESEQUINIL	DM3EAYN	Epilepsy	8A60-8A68	Discontinued in Phase 2	[22]
RO-48-6791	DMH912O	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 2	[23]
SL-65.1498	DMS8AHE	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 2	[24]
Suritozole	DMDZ7AY	Major depressive disorder	6A70.3	Discontinued in Phase 2	[25]
CCD-3693	DMMEC1W	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 1	[26]
CTP-354	DMXY43L	Pain	MG30-MG3Z	Discontinued in Phase 1	[27]
Org-21465	DMMYI9U	Anaesthesia	9A78.6	Discontinued in Phase 1	[28]
RO-48-8684	DMOX8AD	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 1	[29]
Co-152791	DMU5TZD	Epilepsy	8A60-8A68	Terminated	[31]
Girisopam	DMSVMF2	Anxiety disorder	6B00-6B0Z	Terminated	[32]
NSD-721	DMF2XMA	Anxiety disorder	6B00-6B0Z	Terminated	[6]
Ro-19-8022	DMFRCM2	Anxiety disorder	6B00-6B0Z	Terminated	[33]
RU-33965	DMSWFMQ	Alzheimer disease	8A20	Terminated	[34], [35], [36]
ZK-91296	DMJYIVA	Alzheimer disease	8A20	Terminated	[37]
ZK-93426	DMMDQ5T	Alzheimer disease	8A20	Terminated	[38]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RWJ-51204	DMMVS07	Anxiety disorder	6B00-6B0Z	Preclinical	[30]

25 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AA-29504	DMI59T7	Major depressive disorder	6A70.3	Investigative	[6]
alpha3IA	DM257WX	Discovery agent	N.A.	Investigative	[6]
alpha5IA	DMTU5QR	Discovery agent	N.A.	Investigative	[6]
C-21191	DMCAO3V	Anxiety disorder	6B00-6B0Z	Investigative	[6]
CP-409092	DMROYD7	Discovery agent	N.A.	Investigative	[39]
DMCM	DMK3WY4	Discovery agent	N.A.	Investigative	[6]
DOV-51892	DMQIK9S	Panic disorder	6B01	Investigative	[6]
GIDAZEPAM	DMASR6T	Anxiety disorder	6B00-6B0Z	Investigative	[40]
HZ-166	DMLU6VM	Neuropathic pain	8E43.0	Investigative	[6]
Isonipecotic acid	DMO1ZHE	Discovery agent	N.A.	Investigative	[6]
JM-1232(-)	DMWMRO2	Anaesthesia	9A78.6	Investigative	[6]
NGD 96-3	DMWD7I3	Insomnia	7A00-7A0Z	Investigative	[6]
piperidine-4-sulphonic acid	DMMIZWE	Discovery agent	N.A.	Investigative	[6]
PNU 101017	DMKBCS2	Discovery agent	N.A.	Investigative	[41]
Ro-15-3505	DM4NW3U	Discovery agent	N.A.	Investigative	[42]
TBPS	DMFC3XP	Discovery agent	N.A.	Investigative	[6]
tetrahydrodeoxycorticosterone	DMF8M0W	Discovery agent	N.A.	Investigative	[6]
TP003	DMRHDGN	Discovery agent	N.A.	Investigative	[6]
UC-1011	DMCRFT5	Alzheimer disease	8A20	Investigative	[6]
UC-2024	DMJVT4K	Premenstrual syndrome	GA34.40	Investigative	[6]
UC-2029	DMGSOZ7	Premenstrual syndrome	GA34.40	Investigative	[6]
[18F]fluoroethylflumazenil	DMPWART	Discovery agent	N.A.	Investigative	[6]
[35S]TBPS	DMSD51L	Discovery agent	N.A.	Investigative	[6]
[3H]CGS8216	DMLP68J	Inflammation	1A00-CA43.1	Investigative	[6]
[3H]Ro154513	DMMBWKL	Discovery agent	N.A.	Investigative	[6]

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