Target Information

Target General Information

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Target ID

T55285 (Former ID: TTDC00039)

Target Name

Glycine receptor (GlyR)

Synonyms

Glycine receptor

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Gene Name

GLRA1; GLRA2; GLRA3; GLRA4; GLRB

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

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

UniProt ID

GLRA1_HUMAN ; GLRA2_HUMAN ; GLRA3_HUMAN ; GLRA4_HUMAN ; GLRB_HUMAN

Sequence

MYSFNTLRLYLWETIVFFSLAASKEAEAARSAPKPMSPSDFLDKLMGRTSGYDARIRPNF
KGPPVNVSCNIFINSFGSIAETTMDYRVNIFLRQQWNDPRLAYNEYPDDSLDLDPSMLDS
IWKPDLFFANEKGAHFHEITTDNKLLRISRNGNVLYSIRITLTLACPMDLKNFPMDVQTC
IMQLESFGYTMNDLIFEWQEQGAVQVADGLTLPQFILKEEKDLRYCTKHYNTGKFTCIEA
RFHLERQMGYYLIQMYIPSLLIVILSWISFWINMDAAPARVGLGITTVLTMTTQSSGSRA
SLPKVSYVKAIDIWMAVCLLFVFSALLEYAAVNFVSRQHKELLRFRRKRRHHKSPMLNLF
QEDEAGEGRFNFSAYGMGPACLQAKDGISVKGANNSNTTNPPPAPSKSPEEMRKLFIQRA
KKIDKISRIGFPMAFLIFNMFYWIIYKIVRREDVHNQ

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Drugs and Modes of Action

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Approved Drug(s)

[+] 1 Approved Drugs

THIOCOLCHICOSIDE

Drug Info

Approved

Muscle spasm

[2]

Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

MDL-27531

Drug Info

Phase 1

Epilepsy

[3]

UK-240455

Drug Info

Phase 1

Nerve injury

[4]

ZD-9379

Drug Info

Phase 1

Cerebrovascular ischaemia

[5], [6]

Discontinued Drug(s)

[+] 5 Discontinued Drugs

Gavestinel

Drug Info

Discontinued in Phase 2

Nerve injury

[7]

GV-196771

Drug Info

Discontinued in Phase 2

Migraine

[8], [9]

GW 468816

Drug Info

Discontinued in Phase 2

Tobacco dependence

[10]

GINKOLIDE B

Drug Info

Terminated

Sepsis

[11], [12]

M-241247

Drug Info

Terminated

Cerebrovascular ischaemia

[13]

Mode of Action

[+] 4 Modes of Action

Inhibitor

[+] 15 Inhibitor drugs

THIOCOLCHICOSIDE

Drug Info

[1]

GINKOLIDE B

Drug Info

[19]

(12E,20Z,18S)-8-hydroxyvariabilin

Drug Info

[21]

10-methoxy-ginkgolide C

Drug Info

[19]

3,14-DIDEHYDROGINKGOLIDE A

Drug Info

[19]

3-demethoxy-3-D-lyxopyranosylaminothiocolchicine

Drug Info

[1]

3-demethoxy-3-D-mannopyranosylaminothiocolchicine

Drug Info

[1]

3-demethoxy-3-D-xylopyranosylaminothiocolchicine

Drug Info

[1]

3-demethoxy-3-L-fucopyranosylaminothiocolchicine

Drug Info

[1]

3-demethoxy-3D-glucopyranosylaminothiocolchicine

Drug Info

[1]

GINKGOLIDE A

Drug Info

[19]

Ginkgolide C

Drug Info

[19]

Ginkgolide J

Drug Info

[19]

Ginkgolide M

Drug Info

[19]

PICROTIN

Drug Info

[27]

Modulator

[+] 6 Modulator drugs

MDL-27531

Drug Info

[3]

UK-240455

Drug Info

[4], [14]

ZD-9379

Drug Info

[5], [6]

Gavestinel

Drug Info

[15], [16]

GV-196771

Drug Info

[17]

GW 468816

Drug Info

[18]

Antagonist

[+] 5 Antagonist drugs

M-241247

Drug Info

[20]

bilobalide

Drug Info

[24]

ginkgolide X

Drug Info

[24]

PMBA

Drug Info

[28]

[3H]strychnine

Drug Info

[1], [28]

Agonist

[+] 1 Agonist drugs

taurine

Drug Info

[29]

Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"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

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Neuroactive ligand-receptor interaction

Reactome

[+] 1 Reactome Pathways

Ligand-gated ion channel transport

WikiPathways

[+] 1 WikiPathways

Iron uptake and transport

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

Top

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

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

REF 25

Developmental regulation of beta-carboline-induced inhibition of glycine-evoked responses depends on glycine receptor beta subunit expression. Mol Pharmacol. 2005 May;67(5):1783-96.

REF 26

Subunit-specific potentiation of recombinant glycine receptors by NV-31, a bilobalide-derived compound. Neurosci Lett. 2008 Apr 18;435(2):147-51.

REF 27

Mechanisms for picrotoxinin and picrotin blocks of alpha2 homomeric glycine receptors. J Biol Chem. 2007 Jun 1;282(22):16016-35.

REF 28

REF 29

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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