Target Information
Target General Information | Top | |||||
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Target ID |
T55285
(Former ID: TTDC00039)
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Target Name |
Glycine receptor (GlyR)
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Synonyms |
Glycine receptor
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Gene Name |
GLRA1; GLRA2; GLRA3; GLRA4; GLRB
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Tonus and reflex abnormality [ICD-11: MB47] | |||||
Function |
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
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BioChemical Class |
Neurotransmitter receptor
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UniProt ID | ||||||
Sequence |
MYSFNTLRLYLWETIVFFSLAASKEAEAARSAPKPMSPSDFLDKLMGRTSGYDARIRPNF
KGPPVNVSCNIFINSFGSIAETTMDYRVNIFLRQQWNDPRLAYNEYPDDSLDLDPSMLDS IWKPDLFFANEKGAHFHEITTDNKLLRISRNGNVLYSIRITLTLACPMDLKNFPMDVQTC IMQLESFGYTMNDLIFEWQEQGAVQVADGLTLPQFILKEEKDLRYCTKHYNTGKFTCIEA RFHLERQMGYYLIQMYIPSLLIVILSWISFWINMDAAPARVGLGITTVLTMTTQSSGSRA SLPKVSYVKAIDIWMAVCLLFVFSALLEYAAVNFVSRQHKELLRFRRKRRHHKSPMLNLF QEDEAGEGRFNFSAYGMGPACLQAKDGISVKGANNSNTTNPPPAPSKSPEEMRKLFIQRA KKIDKISRIGFPMAFLIFNMFYWIIYKIVRREDVHNQ Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | THIOCOLCHICOSIDE | Drug Info | Approved | Muscle spasm | [2] | |
Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
1 | MDL-27531 | Drug Info | Phase 1 | Epilepsy | [3] | |
2 | UK-240455 | Drug Info | Phase 1 | Nerve injury | [4] | |
3 | ZD-9379 | Drug Info | Phase 1 | Cerebrovascular ischaemia | [5], [6] | |
Discontinued Drug(s) | [+] 5 Discontinued Drugs | + | ||||
1 | Gavestinel | Drug Info | Discontinued in Phase 2 | Nerve injury | [7] | |
2 | GV-196771 | Drug Info | Discontinued in Phase 2 | Migraine | [8], [9] | |
3 | GW 468816 | Drug Info | Discontinued in Phase 2 | Tobacco dependence | [10] | |
4 | GINKOLIDE B | Drug Info | Terminated | Sepsis | [11], [12] | |
5 | M-241247 | Drug Info | Terminated | Cerebrovascular ischaemia | [13] | |
Mode of Action | [+] 4 Modes of Action | + | ||||
Inhibitor | [+] 13 Inhibitor drugs | + | ||||
1 | THIOCOLCHICOSIDE | Drug Info | [1] | |||
2 | GINKOLIDE B | Drug Info | [19] | |||
3 | (12E,20Z,18S)-8-hydroxyvariabilin | Drug Info | [21] | |||
4 | 10-methoxy-ginkgolide C | Drug Info | [19] | |||
5 | 3-demethoxy-3-D-lyxopyranosylaminothiocolchicine | Drug Info | [1] | |||
6 | 3-demethoxy-3-D-mannopyranosylaminothiocolchicine | Drug Info | [1] | |||
7 | 3-demethoxy-3-D-xylopyranosylaminothiocolchicine | Drug Info | [1] | |||
8 | 3-demethoxy-3-L-fucopyranosylaminothiocolchicine | Drug Info | [1] | |||
9 | 3-demethoxy-3D-glucopyranosylaminothiocolchicine | Drug Info | [1] | |||
10 | GINKGOLIDE A | Drug Info | [19] | |||
11 | Ginkgolide C | Drug Info | [19] | |||
12 | Ginkgolide J | Drug Info | [19] | |||
13 | Ginkgolide M | Drug Info | [19] | |||
Modulator | [+] 6 Modulator drugs | + | ||||
1 | MDL-27531 | Drug Info | [3] | |||
2 | UK-240455 | Drug Info | [4], [14] | |||
3 | ZD-9379 | Drug Info | [5], [6] | |||
4 | Gavestinel | Drug Info | [15], [16] | |||
5 | GV-196771 | Drug Info | [17] | |||
6 | GW 468816 | Drug Info | [18] | |||
Antagonist | [+] 5 Antagonist drugs | + | ||||
1 | M-241247 | Drug Info | [20] | |||
2 | bilobalide | Drug Info | [24] | |||
3 | ginkgolide X | Drug Info | [24] | |||
4 | PMBA | Drug Info | [26] | |||
5 | [3H]strychnine | Drug Info | [1], [26] | |||
Agonist | [+] 1 Agonist drugs | + | ||||
1 | taurine | Drug Info | [27] |
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 |
Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
1 | Neuroactive ligand-receptor interaction | |||||
Reactome | [+] 1 Reactome Pathways | + | ||||
1 | Ligand-gated ion channel transport | |||||
WikiPathways | [+] 1 WikiPathways | + | ||||
1 | Iron uptake and transport |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | 3-demethoxy-3-glycosylaminothiocolchicines: Synthesis of a new class of putative muscle relaxant compounds. J Med Chem. 2006 Sep 7;49(18):5571-7. | |||||
REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 3 | MDL 27,531 reduces spontaneous hindlimb contractions in rats with chronic transections of the spinal cord. Neurosci Lett. 1992 Nov 23;147(1):101-5. | |||||
REF 4 | UK-315716/UK-240455. Pfizer. Curr Opin Investig Drugs. 2001 Dec;2(12):1737-9. | |||||
REF 5 | Neuroprotective potential of ionotropic glutamate receptor antagonists. Neurotox Res. 2002 Mar;4(2):119-26. | |||||
REF 6 | A glycine site antagonist, ZD9379, reduces number of spreading depressions and infarct size in rats with permanent middle cerebral artery occlusion. Stroke. 1998 Jan;29(1):190-5. | |||||
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 800007924) | |||||
REF 8 | 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: 4208). | |||||
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 800008901) | |||||
REF 10 | Executive summary: nicotine addiction. Drugs Today (Barc). 2005 Jun;41(6):419-25. | |||||
REF 11 | 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: 1862). | |||||
REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000117) | |||||
REF 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003415) | |||||
REF 14 | Pharmacokinetics and disposition of a novel NMDA glycine site antagonist (UK-240,455) in rats, dogs and man. Xenobiotica. 2003 May;33(5):541-60. | |||||
REF 15 | Glycine antagonist (gavestinel) in neuroprotection (GAIN International) in patients with acute stroke: a randomised controlled trial.GAIN International Investigators.Lancet.2000 Jun 3;355(9219):1949-54. | |||||
REF 16 | Effect of the Glycine Antagonist Gavestinel on cerebral infarcts in acute stroke patients, a randomized placebo-controlled trial: The GAIN MRI Substudy.Cerebrovasc Dis.2006;21(1-2):106-11. | |||||
REF 17 | First time in human for GV196771: interspecies scaling applied on dose selection. J Clin Pharmacol. 1999 Jun;39(6):560-6. | |||||
REF 18 | A double-blind, placebo-controlled trial of the NMDA glycine site antagonist, GW468816, for prevention of relapse to smoking in females.J Clin Psychopharmacol.2011 Oct;31(5):597-602. | |||||
REF 19 | Probing the pharmacophore of ginkgolides as glycine receptor antagonists. J Med Chem. 2007 Apr 5;50(7):1610-7. | |||||
REF 20 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003415) | |||||
REF 21 | Ircinialactams: subunit-selective glycine receptor modulators from Australian sponges of the family Irciniidae. Bioorg Med Chem. 2010 Apr 15;18(8):2912-9. | |||||
REF 22 | Selective actions of a detergent on ligand-gated ion channels expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1998 Jan;284(1):32-6. | |||||
REF 23 | Subunit-specific action of an anticonvulsant thiobutyrolactone on recombinant glycine receptors involves a residue in the M2 membrane-spanning region. Mol Pharmacol. 2000 Jul;58(1):11-7. | |||||
REF 24 | 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: 427). | |||||
REF 25 | Subunit-specific potentiation of recombinant glycine receptors by NV-31, a bilobalide-derived compound. Neurosci Lett. 2008 Apr 18;435(2):147-51. | |||||
REF 26 | 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: 425). | |||||
REF 27 | Identification of intracellular and extracellular domains mediating signal transduction in the inhibitory glycine receptor chloride channel. EMBO J. 1997 Jan 2;16(1):110-20. |
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