Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTGXH6N)

• DTT Name: GABA(A) receptor delta (GABRD)
• Synonyms: Gammaaminobutyric acid receptor subunit delta; GABRD; GABA(A) receptor subunit delta
• Gene Name: GABRD
• DTT Type: Successful target; [1]
• BioChemical Class: Ligand-gated ion channel
• UniProt ID: GBRD_HUMAN
• TTD ID: T27376
• Sequence:
  MDAPARLLAPLLLLCAQQLRGTRAMNDIGDYVGSNLEISWLPNLDGLIAGYARNFRPGIG
  GPPVNVALALEVASIDHISEANMEYTMTVFLHQSWRDSRLSYNHTNETLGLDSRFVDKLW
  LPDTFIVNAKSAWFHDVTVENKLIRLQPDGVILYSIRITSTVACDMDLAKYPMDEQECML
  DLESYGYSSEDIVYYWSESQEHIHGLDKLQLAQFTITSYRFTTELMNFKSAGQFPRLSLH
  FHLRRNRGVYIIQSYMPSVLLVAMSWVSFWISQAAVPARVSLGITTVLTMTTLMVSARSS
  LPRASAIKALDVYFWICYVFVFAALVEYAFAHFNADYRKKQKAKVKVSRPRAEMDVRNAI
  VLFSLSAAGVTQELAISRRQRRVPGNLMGSYRSVGVETGETKKEGAARSGGQGGIRARLR
  PIDADTIDIYARAVFPAAFAAVNVIYWAAYAM
• Function: GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Retrograde endocannabinoid signaling (hsa04723)
  GABAergic synapse (hsa04727)
  Morphine addiction (hsa05032)
  Nicotine addiction (hsa05033)

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Allopregnanolone	DMNLHAC	Depression	6A70-6A7Z	approved	[2]
Gaboxadol	DMI53FU	Insomnia	7A00-7A0Z	Approved	[1]
Ganaxolone	DMXJMKF	Epileptic seizures	8A61-8A6Z	Approved	[3]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SAGE-217b	DMRFK0B	Major depressive disorder	6A70.3	Phase 2	[2]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-4480682	DMWYJHC	Neuropathic pain	8E43.0	Discontinued in Phase 2	[4]
PF-2393296	DM5R2MG	Neuropathic pain	8E43.0	Discontinued in Phase 1	[5]
Co-60549	DMGIZHX	Anxiety disorder	6B00-6B0Z	Terminated	[6]
Org-20599	DMQU8AR	Anaesthesia	9A78.6	Terminated	[7]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RU-5135	DMCASRD	Discovery agent	N.A.	Investigative	[8]
TBPS	DMFC3XP	Discovery agent	N.A.	Investigative	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Major depressive disorder	6A20	Pre-frontal cortex	7.17E-01	-0.14	-0.19

References

• [1] Gaboxadol--a new awakening in sleep.Curr Opin Pharmacol.2006 Feb;6(1):30-6.
• [2] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [3] Ganaxolone, a selective, high-affinity steroid modulator of the gamma-aminobutyric acid-A receptor, exacerbates seizures in animal models of absence. Ann Neurol. 1998 Oct;44(4):688-91.
• [4] WO patent application no. 2014,1515,17, Methods of improving microvascular integrity.
• [5] URL: 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: 416).
• [6] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007012)
• [7] The anaesthetic action and modulation of GABAA receptor activity by the novel water-soluble aminosteroid Org 20599. Neuropharmacology. 1996;35(9-10):1209-22.
• [8] Complex interactions between the steroid derivative RU 5135 and the GABAA-receptor complex. Eur J Pharmacol. 1992 Oct 1;227(2):147-51.