BREXPIPRAZOLE

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Trade Names
Synonyms
Status
Molecule Category UNKNOWN
ATC N05AX16
UNII 2J3YBM1K8C
EPA CompTox DTXSID40238527

Structure

InChI Key ZKIAIYBUSXZPLP-UHFFFAOYSA-N
Smiles O=c1ccc2ccc(OCCCCN3CCN(c4cccc5sccc45)CC3)cc2[nH]1
InChI
InChI=1S/C25H27N3O2S/c29-25-9-7-19-6-8-20(18-22(19)26-25)30-16-2-1-11-27-12-14-28(15-13-27)23-4-3-5-24-21(23)10-17-31-24/h3-10,17-18H,1-2,11-16H2,(H,26,29)

Physicochemical Descriptors

Property Name Value
Molecular Formula C25H27N3O2S
Molecular Weight 433.58
AlogP 4.72
Hydrogen Bond Acceptor 5.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 7.0
Polar Surface Area 48.57
Molecular species NEUTRAL
Aromatic Rings 4.0
Heavy Atoms 31.0

Bioactivity

Mechanism of Action Action Reference
Dopamine D2 receptor partial agonist PARTIAL AGONIST FDA
Protein: Serotonin 1a (5-HT1a) receptor
Description: 5-hydroxytryptamine receptor 1A
Organism : Homo sapiens
P08908 ENSG00000178394
Protein: Dopamine D2 receptor
Description: D(2) dopamine receptor
Organism : Homo sapiens
P14416 ENSG00000149295
Protein: Serotonin 2a (5-HT2a) receptor
Description: 5-hydroxytryptamine receptor 2A
Organism : Homo sapiens
P28223 ENSG00000102468
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Membrane receptor Family A G protein-coupled receptor Small molecule receptor (family A GPCR) Monoamine receptor Dopamine receptor
6 - - 0-0 -
Membrane receptor Family A G protein-coupled receptor Small molecule receptor (family A GPCR) Monoamine receptor Serotonin receptor
- - - 0-0 -
Assay Description Organism Bioactivity Reference
Dopamine D2 Receptor Binding Assay: The assay was performed according to the method by Kohler et al. (Kohler C, Hall H, Ogren S O and Gawell L, Specific in vitro and in vivo binding of 3H-raclopride. A potent substituted benzamide drug with high affinity for dopamine D-2 receptors in the rat brain. Biochem. Pharmacol., 1985; 34: 2251-2259). The binding assay was performed using 40 ul of the membrane specimen, 20 ul of [3H]-raclopride (final concentration 1 to 2 nM), 20 ul of a test drug and 50 mM Tris-hydrochloric acid buffer (containing 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, pH 7.4) so that the total amount was 200 ul (final dimethylsulfoxide concentration 1%). The reaction was performed at room temperature for 1 hour and terminated by conducting suction filtration with a cell harvester on a glass fiber filter plate. The filter plate made of glass fiber was washed with 50 mM Tris-hydrochloric acid buffer (pH 7.4), and after dried, a microplate liquid scintillation cocktail was added. Rattus norvegicus 0.2 nM
Serotonin 5-HT2A Receptor Binding Assay: The assay was performed according to the method by Leysen J E et al. (Leysen J E, Niemegeers C J E, Van Nueten J M and Laduron P M. [3H] Ketanserin (R 41 468), a selective 3H-ligand for serotonin 2 receptor binding sites. Mol. Pharmacol., 1982, 21: 301-314). The binding assay was performed using 40 ul of the membrane specimen, 20 ul of [3H]-Ketanserin (final concentration 1 to 3 nM), 20 ul of a test drug and 50 mM Tris-hydrochloric acid buffer (pH 7.4) so that the total amount was 200 ul (final dimethylsulfoxide concentration 1%). The reaction was performed at 37° C. for 20 minutes and terminated by conducting suction filtration with a cell harvester on a glass fiber filter plate.The filter plate made of glass fiber was washed with 50 mM Tris-hydrochloric acid buffer (pH 7.4), and after dried, a microplate liquid scintillation cocktail was added and the radioactivity was measured with a microplate scintillation counter. Rattus norvegicus 2.3 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens 10.39 %
Displacement of [3H]-8-OH-DPAT from 5HT1A receptor in rat brain hippocampus incubated for 60 mins by radioligand binding assay Rattus norvegicus 0.09 nM
Displacement of [3H]raclopride from D2 receptor in rat brain striatum incubated for 60 mins by radioligand binding assay Rattus norvegicus 3.8 nM
Binding affinity to 5-HT2BR (unknown origin) Homo sapiens 0.3981 nM
Displacement of [3H]-8-OH-DPAT from human 5HT1A receptor expressed in CHO-K1 cell membranes incubated for 60 mins by microbeta scintillation counting analysis Homo sapiens 0.12 nM
Displacement of [3H]-Ketanserin from human 5-HT2A receptor expressed in rat cortex tissue incubated for 30 mins by liquid scintillation counting method Homo sapiens 0.47 nM
Displacement of [3H]-raclopride from human D2L receptor expressed in HEK293 cells incubated for 1 hr by liquid scintillation counting method Homo sapiens 0.3 nM
Displacement of [3H]-5-CT from human 5HT7 receptor expressed in HEK293 cells incubated for 1 hr by liquid scintillation counting method Homo sapiens 3.7 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 11.11 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 21.26 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.56 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.48 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.48 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.56 %
Agonist activity at D2 receptor (unknown origin) Homo sapiens 6.3 nM
Cytotoxicity against human Chang cells assessed as reduction in cell viability Homo sapiens 44.2 ug.mL-1
Cytotoxicity against human HEK293 cells assessed as reduction in cell viability Homo sapiens 19.1 ug.mL-1
Displacement of [3H](+)8-OH-DPAT from human 5HT1A receptor expressed in human HeLa cells measured after 60 mins Homo sapiens 0.12 nM
Displacement of [3H]raclopride from human D2 long receptor expressed in CHO cells measured after 60 mins Homo sapiens 0.3 nM
Displacement of [3H]ketanserin from human 5HT2A receptor expressed in CHO-K1 cells measured after 20 mins Homo sapiens 0.47 nM
Displacement of [3H]-N-methylspiperone from D2 receptor (unknown origin) expressed in HEK293T cell membranes measured after 2 hrs by microbeta scintillation counting method Homo sapiens 0.51 nM Displacement of [3H]-N-methylspiperone from D2 receptor (unknown origin) expressed in HEK293T cell membranes measured after 2 hrs by microbeta scintillation counting method Homo sapiens 0.5129 nM
Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T cells co-expressing Rluc8-tagged Galpahi1 assessed as Galphai1 dissociation preincubated for 2 mins with coelenterazine followed by compound addition and measured after 2 mins by BRET assay Homo sapiens 10.2 nM Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T cells co-expressing Rluc8-tagged Galpahi1 assessed as Galphai1 dissociation preincubated for 2 mins with coelenterazine followed by compound addition and measured after 2 mins by BRET assay Homo sapiens 10.0 nM
Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T cells co-expressing GFP2-beta-arrestin2 assessed as beta-arrestin2 recruitment preincubated for 2 mins with coelenterazine followed by compound addition and measured after 2 mins by BRET assay Homo sapiens 16.1 nM Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T cells co-expressing GFP2-beta-arrestin2 assessed as beta-arrestin2 recruitment preincubated for 2 mins with coelenterazine followed by compound addition and measured after 2 mins by BRET assay Homo sapiens 16.22 nM

Cross References

Resources Reference
ChEBI 134716
ChEMBL CHEMBL2105760
DrugBank DB09128
DrugCentral 5014
FDA SRS 2J3YBM1K8C
Guide to Pharmacology 7672
PharmGKB PA166160053
PubChem 11978813
SureChEMBL SCHEMBL1037592
ZINC ZINC000084758479
CONTENTS