Target Information
| Target General Information | Top | |||||
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| Target ID |
T27376
(Former ID: TTDI01909)
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| Target Name |
GABA(A) receptor delta (GABRD)
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| Synonyms |
Gammaaminobutyric acid receptor subunit delta; GABRD; GABA(A) receptor subunit delta
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| Gene Name |
GABRD
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Depression [ICD-11: 6A70-6A7Z] | |||||
| 2 | Insomnia [ICD-11: 7A00-7A0Z] | |||||
| 3 | Mental/behavioural/neurodevelopmental disorder [ICD-11: 6E20-6E8Z] | |||||
| 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.
Click to Show/Hide
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| BioChemical Class |
Ligand-gated ion channel
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| UniProt ID | ||||||
| Sequence |
MDAPARLLAPLLLLCAQQLRGTRAMNDIGDYVGSNLEISWLPNLDGLIAGYARNFRPGIG
GPPVNVALALEVASIDHISEANMEYTMTVFLHQSWRDSRLSYNHTNETLGLDSRFVDKLW LPDTFIVNAKSAWFHDVTVENKLIRLQPDGVILYSIRITSTVACDMDLAKYPMDEQECML DLESYGYSSEDIVYYWSESQEHIHGLDKLQLAQFTITSYRFTTELMNFKSAGQFPRLSLH FHLRRNRGVYIIQSYMPSVLLVAMSWVSFWISQAAVPARVSLGITTVLTMTTLMVSARSS LPRASAIKALDVYFWICYVFVFAALVEYAFAHFNADYRKKQKAKVKVSRPRAEMDVRNAI VLFSLSAAGVTQELAISRRQRRVPGNLMGSYRSVGVETGETKKEGAARSGGQGGIRARLR PIDADTIDIYARAVFPAAFAAVNVIYWAAYAM Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | Allopregnanolone | Drug Info | Approved | Postpartum depression | [2], [3] | |
| 2 | Gaboxadol | Drug Info | Approved | Insomnia | [4], [5] | |
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | Ganaxolone | Drug Info | Phase 3 | Complex partial seizure | [6] | |
| 2 | SAGE-217b | Drug Info | Phase 2 | Major depressive disorder | [2] | |
| Discontinued Drug(s) | [+] 4 Discontinued Drugs | + | ||||
| 1 | PF-4480682 | Drug Info | Discontinued in Phase 2 | Neuropathic pain | [7] | |
| 2 | PF-2393296 | Drug Info | Discontinued in Phase 1 | Neuropathic pain | [8] | |
| 3 | Co-60549 | Drug Info | Terminated | Anxiety disorder | [9] | |
| 4 | Org-20599 | Drug Info | Terminated | Anaesthesia | [10] | |
| Mode of Action | [+] 5 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | Allopregnanolone | Drug Info | [2] | |||
| Modulator | [+] 6 Modulator drugs | + | ||||
| 1 | Gaboxadol | Drug Info | [1] | |||
| 2 | Ganaxolone | Drug Info | [11] | |||
| 3 | PF-4480682 | Drug Info | [12] | |||
| 4 | Co-60549 | Drug Info | [14] | |||
| 5 | Org-20599 | Drug Info | [15] | |||
| 6 | RU-5135 | Drug Info | [16] | |||
| Immunostimulant | [+] 1 Immunostimulant drugs | + | ||||
| 1 | SAGE-217b | Drug Info | [2] | |||
| Agonist | [+] 1 Agonist drugs | + | ||||
| 1 | PF-2393296 | Drug Info | [13] | |||
| Blocker (channel blocker) | [+] 1 Blocker (channel blocker) drugs | + | ||||
| 1 | TBPS | Drug Info | [13] | |||
| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| 2 | Retrograde endocannabinoid signaling | |||||
| 3 | GABAergic synapse | |||||
| 4 | Morphine addiction | |||||
| 5 | Nicotine addiction | |||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Gaboxadol--a new awakening in sleep.Curr Opin Pharmacol.2006 Feb;6(1):30-6. | |||||
| REF 2 | Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357. | |||||
| REF 3 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 4 | 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. (Ligand id: 4322). | |||||
| REF 5 | Highway driving performance and cognitive functioning the morning after bedtime and middle-of-the-night use of gaboxadol, zopiclone and zolpidem. J Sleep Res. 2009 Dec;18(4):387-96. | |||||
| REF 6 | ClinicalTrials.gov (NCT01963208) Phase 3 Study of Adjunctive Ganaxolone in Adults With Drug-resistant Partial Onset Seizures and Open-label Extension. U.S. National Institutes of Health. | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025530) | |||||
| REF 8 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027949) | |||||
| REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007012) | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003651) | |||||
| REF 11 | 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. | |||||
| REF 12 | WO patent application no. 2014,1515,17, Methods of improving microvascular integrity. | |||||
| REF 13 | 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). | |||||
| REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007012) | |||||
| REF 15 | The anaesthetic action and modulation of GABAA receptor activity by the novel water-soluble aminosteroid Org 20599. Neuropharmacology. 1996;35(9-10):1209-22. | |||||
| REF 16 | Complex interactions between the steroid derivative RU 5135 and the GABAA-receptor complex. Eur J Pharmacol. 1992 Oct 1;227(2):147-51. | |||||
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