Details
Stereochemistry | ACHIRAL |
Molecular Formula | C18H11Cl2N2O3.Na |
Molecular Weight | 397.187 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].[O-]C(=O)C1=C(\C=C\C(=O)NC2=CC=CC=C2)C3=C(N1)C=C(Cl)C=C3Cl
InChI
InChIKey=GRSDSTMFQHAESM-UHDJGPCESA-M
InChI=1S/C18H12Cl2N2O3.Na/c19-10-8-13(20)16-12(17(18(24)25)22-14(16)9-10)6-7-15(23)21-11-4-2-1-3-5-11;/h1-9,22H,(H,21,23)(H,24,25);/q;+1/p-1/b7-6+;
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/9083472Curator's Comment: Description was created using several sources including:
https://www.ncbi.nlm.nih.gov/pubmed/16340185; https://www.ncbi.nlm.nih.gov/pubmed/15831831
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9083472
Curator's Comment: Description was created using several sources including:
https://www.ncbi.nlm.nih.gov/pubmed/16340185; https://www.ncbi.nlm.nih.gov/pubmed/15831831
GV 150526A (gavestinel) is an investigational drug for a neuroprotective therapy of acute ischemic stroke within 6 hours of symptom onset. It is a potent and selective non-competitive antagonist at the glycine site of the N-methyl-D-aspartate receptor (NMDA) which reduces infarct volume in experimental stroke models. Gavestinel acts at the strychnine-insensitive glycine binding site of the NMDA receptor-channel complex with nanomolar affinity (pKi = 8.5), coupled with high glutamate receptor selectivity. Gavestinel displays higher than 1000-fold selectivity over NMDA, AMPA and kainate binding sites and is orally bioavailable and active in vivo. GV 150526A inhibited convulsions induced by NMDA in mice, when administered by both IV and po routes (ED50 = 0.06 and 6 mg/kg, respectively). The safety and efficacy of GV150526 were studied in two phase III randomized placebo-controlled clinical trials of acute ischemic stroke patients within 6 h from onset [The Glycine Antagonist in Neuroprotection (GAIN) International and GAIN Americas Trials] sponsored by GlaxoSmithKline. The results of these trials suggested that gavestinel was not of substantial benefit or harm to patients with primary intracerebral hemorrhage.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16340185 |
|||
Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9384243 |
8.5 null [pKi] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
135 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10805066 |
400 mg 2 times / day steady-state, intravenous dose: 400 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
GV 150526A plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
55.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10805066 |
400 mg 2 times / day steady-state, intravenous dose: 400 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
GV 150526A plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.6% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10805066 |
400 mg 2 times / day steady-state, intravenous dose: 400 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
GV 150526A plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
inconclusive [IC50 15.8489 uM] | ||||
likely | ||||
major | ||||
minor [IC50 10.6 uM] | ||||
minor | ||||
minor | ||||
no [IC50 15.8489 uM] | ||||
yes [IC50 <10 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Substituted indole-2-carboxylates as in vivo potent antagonists acting as the strychnine-insensitive glycine binding site. | 1997 Mar 14 |
|
Synthesis and pharmacological characterisation of a conformationally restrained series of indole-2-carboxylates as in vivo potent glycine antagonists. | 2001 Oct |
|
Gavestinel does not improve outcome after acute intracerebral hemorrhage: an analysis from the GAIN International and GAIN Americas studies. | 2005 May |
|
Effect of the Glycine Antagonist Gavestinel on cerebral infarcts in acute stroke patients, a randomized placebo-controlled trial: The GAIN MRI Substudy. | 2006 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11277826
Gavestinel loading dose of 800 mg plus 5 maintenance doses (200 mg every 12 hours) for 3 days.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9413843
The effect of selective antagonist GV 150526A at trychnine-insensitive glycine sites was studied by measuring how much glycine potentiated the [3H]dopamine and [3H]noradrenaline release induced by 100 uM N-methyl-D-aspartate (NMDA) from superfused striatal and hippocampal synaptosomes in a Mg2+-free buffer. GV 150526A inhibited the effect of NMDA alone and potently antagonized the effect of glycine, with Ki = 12.4 and 17.3 nM for [3H]dopamine and [3H]noradrenaline release.
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80W7787JVB
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C105319
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DTXSID20165327
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153436-38-5
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DBSALT002362
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16759177
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ACTIVE MOIETY
SUBSTANCE RECORD