Identification
NameGavestinel
Accession NumberDB06741
TypeSmall Molecule
GroupsInvestigational
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
SynonymsNot Available
External IDs GV 150526X / GV-150,526A / GV-150526X
Product Ingredients
IngredientUNIICASInChI KeyDetails
Gv 150526a80W7787JVB 153436-38-5GRSDSTMFQHAESM-UHDJGPCESA-MDetails
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII318X4QY113
CAS number153436-22-7
WeightAverage: 375.21
Monoisotopic: 374.0224977
Chemical FormulaC18H12Cl2N2O3
InChI KeyWZBNEZWCNKUOSM-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
IndicationNot Available
Structured Indications Not Available
PharmacodynamicsNot Available
Mechanism of action
TargetKindPharmacological actionActionsOrganismUniProt ID
Glutamate (NMDA) receptorProtein groupunknown
antagonist
Humannot applicabledetails
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
SubstrateEnzymesProduct
Gavestinel
p-HydroxygavestinelDetails
Gavestinel
Gavestinel acyl glucuronideDetails
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot 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
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
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
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
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
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 InteractionsNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (608 KB)
Clinical Trials
Clinical Trials Not Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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 featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassIndolecarboxylic acids and derivatives
Direct ParentIndolecarboxylic acids and derivatives
Alternative ParentsIndoles / Anilides / Pyrrole 2-carboxylic acids / N-arylamides / Substituted pyrroles / Aryl chlorides / Heteroaromatic compounds / Secondary carboxylic acid amides / Carboxylic acids / Azacyclic compounds
SubstituentsIndolecarboxylic acid derivative / Indole / Anilide / Pyrrole-2-carboxylic acid / Pyrrole-2-carboxylic acid or derivatives / N-arylamide / Benzenoid / Aryl halide / Substituted pyrrole / Monocyclic benzene moiety
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot 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 plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors (By similarity).
Components:
NameUniProt IDDetails
Glutamate receptor ionotropic, NMDA 1Q05586 Details
Glutamate receptor ionotropic, NMDA 2AQ12879 Details
Glutamate receptor ionotropic, NMDA 2BQ13224 Details
Glutamate receptor ionotropic, NMDA 2CQ14957 Details
Glutamate receptor ionotropic, NMDA 2DO15399 Details
Glutamate receptor ionotropic, NMDA 3AQ8TCU5 Details
Glutamate receptor ionotropic, NMDA 3BO60391 Details
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
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 IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naph...
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 regulator of isoform 1.
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 transferase activity but acts as a negative regulator of isoform 1.
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 estriol, 4-hydroxyestrone and 2-hydroxyestriol) and xenobiotics (such as 4-methylumbelliferone, 1-naphthol, 4-nitrophenol, 2-aminophenol, 4-hydroxybiphenyl and menthol). It is capable of 6 alpha-hydr...
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 September 01, 2017 11:30