Identification

Name
Gavestinel
Accession Number
DB06741
Type
Small Molecule
Groups
Investigational
Description

Highly potent and selective non-competitive antagonist acting at the strychnine-insensitive glycine binding site of the NMDA receptor-channel complex (Kd = 0.8 nM). Gavestinel displays > 1000-fold selectivity over NMDA, AMPA and kainate binding sites and is orally bioavailable and active in vivo.

Structure
Thumb
Synonyms
Not Available
External IDs
GV 150526X / GV-150,526A / GV-150526X
Product Ingredients
IngredientUNIICASInChI Key
Gv 150526a80W7787JVB153436-38-5GRSDSTMFQHAESM-UHDJGPCESA-M
Categories
UNII
318X4QY113
CAS number
153436-22-7
Weight
Average: 375.21
Monoisotopic: 374.0224977
Chemical Formula
C18H12Cl2N2O3
InChI Key
WZBNEZWCNKUOSM-VOTSOKGWSA-N
InChI
InChI=1S/C18H12Cl2N2O3/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)/b7-6+
IUPAC Name
4,6-dichloro-3-[(1E)-2-(phenylcarbamoyl)eth-1-en-1-yl]-1H-indole-2-carboxylic acid
SMILES
OC(=O)C1=C(\C=C\C(=O)NC2=CC=CC=C2)C2=C(Cl)C=C(Cl)C=C2N1

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UGlutamate (NMDA) receptor
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe metabolism of Gavestinel can be decreased when combined with Abiraterone.Approved
AmiodaroneThe metabolism of Gavestinel can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe metabolism of Gavestinel can be increased when combined with Aprepitant.Approved, Investigational
CapecitabineThe metabolism of Gavestinel can be decreased when combined with Capecitabine.Approved, Investigational
CarbamazepineThe metabolism of Gavestinel can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Gavestinel can be increased when it is combined with Ceritinib.Approved
CholecalciferolThe metabolism of Gavestinel can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
ClotrimazoleThe metabolism of Gavestinel can be decreased when combined with Clotrimazole.Approved, Vet Approved
CrisaboroleThe metabolism of Gavestinel can be decreased when combined with Crisaborole.Approved
CyclosporineThe metabolism of Gavestinel can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Gavestinel can be decreased when it is combined with Dabrafenib.Approved
DelavirdineThe metabolism of Gavestinel can be decreased when combined with Delavirdine.Approved
DosulepinThe metabolism of Gavestinel can be decreased when combined with Dosulepin.Approved
EfavirenzThe metabolism of Gavestinel can be decreased when combined with Efavirenz.Approved, Investigational
EtravirineThe metabolism of Gavestinel can be decreased when combined with Etravirine.Approved
FloxuridineThe metabolism of Gavestinel can be decreased when combined with Floxuridine.Approved
FluconazoleThe metabolism of Gavestinel can be decreased when combined with Fluconazole.Approved
FluorouracilThe metabolism of Gavestinel can be decreased when combined with Fluorouracil.Approved
FluvastatinThe metabolism of Gavestinel can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Gavestinel can be decreased when combined with Fluvoxamine.Approved, Investigational
FosphenytoinThe metabolism of Gavestinel can be increased when combined with Fosphenytoin.Approved
GemfibrozilThe metabolism of Gavestinel can be decreased when combined with Gemfibrozil.Approved
IndinavirThe metabolism of Gavestinel can be decreased when combined with Indinavir.Approved
IrbesartanThe metabolism of Gavestinel can be decreased when combined with Irbesartan.Approved, Investigational
KetoconazoleThe metabolism of Gavestinel can be decreased when combined with Ketoconazole.Approved, Investigational
LeflunomideThe metabolism of Gavestinel can be decreased when combined with Leflunomide.Approved, Investigational
LobeglitazoneThe metabolism of Gavestinel can be decreased when combined with Lobeglitazone.Approved, Investigational
LosartanThe metabolism of Gavestinel can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Gavestinel can be decreased when combined with Lovastatin.Approved, Investigational
LumacaftorThe serum concentration of Gavestinel can be decreased when it is combined with Lumacaftor.Approved
ManidipineThe metabolism of Gavestinel can be decreased when combined with Manidipine.Approved, Investigational
MidostaurinThe metabolism of Gavestinel can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Gavestinel can be increased when it is combined with Mifepristone.Approved, Investigational
NicardipineThe metabolism of Gavestinel can be decreased when combined with Nicardipine.Approved
OmeprazoleThe metabolism of Gavestinel can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
PhenobarbitalThe metabolism of Gavestinel can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Gavestinel can be increased when combined with Phenytoin.Approved, Vet Approved
PrimidoneThe metabolism of Gavestinel can be increased when combined with Primidone.Approved, Vet Approved
PyrimethamineThe metabolism of Gavestinel can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuinineThe metabolism of Gavestinel can be decreased when combined with Quinine.Approved
RifampicinThe metabolism of Gavestinel can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Gavestinel can be increased when combined with Rifapentine.Approved
SecobarbitalThe metabolism of Gavestinel can be increased when combined with Secobarbital.Approved, Vet Approved
SildenafilThe metabolism of Gavestinel can be decreased when combined with Sildenafil.Approved, Investigational
SorafenibThe metabolism of Gavestinel can be decreased when combined with Sorafenib.Approved, Investigational
SulfadiazineThe metabolism of Gavestinel can be decreased when combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Gavestinel can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Gavestinel can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TicagrelorThe metabolism of Gavestinel can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Gavestinel can be decreased when combined with Ticlopidine.Approved
TolbutamideThe metabolism of Gavestinel can be decreased when combined with Tolbutamide.Approved
TopiroxostatThe metabolism of Gavestinel can be decreased when combined with Topiroxostat.Approved, Investigational
TrimethoprimThe metabolism of Gavestinel can be decreased when combined with Trimethoprim.Approved, Vet Approved
Valproic AcidThe metabolism of Gavestinel can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Gavestinel can be decreased when combined with Valsartan.Approved, Investigational
VoriconazoleThe metabolism of Gavestinel can be decreased when combined with Voriconazole.Approved, Investigational
ZafirlukastThe metabolism of Gavestinel can be decreased when combined with Zafirlukast.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Warach S, Kaufman D, Chiu D, Devlin T, Luby M, Rashid A, Clayton L, Kaste M, Lees KR, Sacco R, Fisher M: 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. Epub 2005 Dec 9. [PubMed:16340185]
External Links
PubChem Compound
6450546
PubChem Substance
347827789
ChemSpider
4953148
BindingDB
50010475
ChEMBL
CHEMBL44793
Wikipedia
Gavestinel
MSDS
Download (608 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0012 mg/mLALOGPS
logP4.18ALOGPS
logP4.45ChemAxon
logS-5.5ALOGPS
pKa (Strongest Acidic)5.04ChemAxon
pKa (Strongest Basic)-2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area82.19 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity99.17 m3·mol-1ChemAxon
Polarizability36.97 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as indolecarboxylic acids and derivatives. These are compounds containing a carboxylic acid group (or a derivative thereof) linked to an indole.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Indolecarboxylic acids and derivatives
Direct Parent
Indolecarboxylic acids and derivatives
Alternative Parents
Indoles / Anilides / Pyrrole 2-carboxylic acids / N-arylamides / Substituted pyrroles / Aryl chlorides / Heteroaromatic compounds / Secondary carboxylic acid amides / Carboxylic acids / Azacyclic compounds
show 4 more
Substituents
Indolecarboxylic acid derivative / Indole / Anilide / Pyrrole-2-carboxylic acid / Pyrrole-2-carboxylic acid or derivatives / N-arylamide / Benzenoid / Aryl halide / Substituted pyrrole / Monocyclic benzene moiety
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Voltage-gated cation channel activity
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic p...

Components:
References
  1. Warach S, Kaufman D, Chiu D, Devlin T, Luby M, Rashid A, Clayton L, Kaste M, Lees KR, Sacco R, Fisher M: 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. Epub 2005 Dec 9. [PubMed:16340185]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as...
Gene Name
UGT2B4
Uniprot ID
P06133
Uniprot Name
UDP-glucuronosyltransferase 2B4
Molecular Weight
60512.035 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]

Drug created on August 31, 2010 15:30 / Updated on November 09, 2017 03:55