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Compound Detail

CHEMBL2105760

BREXPIPRAZOLE
💊 Approved Drug
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💊 Approved Drug
O=c1ccc2ccc(OCCCCN3CCN(c4cccc5sccc45)CC3)cc2[nH]1

Basic Information

ChEMBL ID CHEMBL2105760
Name BREXPIPRAZOLE
Phase Approved
Structure Type MOL
InChI Key ZKIAIYBUSXZPLP-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

Brexpiprazol Brexpiprazole OPC-34712 Rexulti Rxulti
36
Targets
51
Activities
3
Assay Types
2
PK Parameters
20
Publications
5
Known Names
14
Indications
3
Mechanisms

Molecular Properties

433.6
MW (Da)
4.72
ALogP
5
HBA
1
HBD
48.6
PSA (Ų)
0.43
QED
0
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2015
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

Black Box Warning Natural Product
USAN Stem -prazole
USAN Year 2011

Extended Properties

Molecular Formula C25H27N3O2S
MW 433.58
Aromatic Rings 4
Heavy Atoms 31
NP-Likeness -1.48

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Dopamine D2 receptor partial agonist PARTIAL AGONIST D(2) dopamine receptor
Serotonin 1a (5-HT1a) receptor partial agonist PARTIAL AGONIST 5-hydroxytryptamine receptor 1A
Serotonin 2a (5-HT2a) receptor antagonist ANTAGONIST 5-hydroxytryptamine receptor 2A

Indications

Depressive Disorder, Major Psychotic Disorders Psychotic Disorders Schizophrenia Alzheimer Disease Bipolar Disorder Bipolar Disorder Depressive Disorder Mental Disorders Psychomotor Agitation Sleep Wake Disorders Stress Disorders, Post-Traumatic Alcoholism Borderline Personality Disorder

ATC Classification

N05AX16
brexpiprazole
Level 1: NERVOUS SYSTEM
Level 2: PSYCHOLEPTICS

Drug Warnings

Black Box Warning
psychiatric toxicity
Country: United States

Activity Summary

Ki 44 meas. best 10.05
EC50 5 meas. best 8.2
IC50 2 meas. best 5.44

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
5-hydroxytryptamine receptor 1A
CHEMBL273
Ki 10.05 10.05 0.1 1
5-hydroxytryptamine receptor 1A
CHEMBL214
Ki 9.92 9.1567 0.1 3
D(2) dopamine receptor
CHEMBL339
Ki 9.7 9.06 0.2 2
D(2) dopamine receptor
CHEMBL217
Ki 9.52 9.168 0.3 5
5-hydroxytryptamine receptor 2B
CHEMBL1833
Ki 9.4 9.4 0.4 1
5-hydroxytryptamine receptor 2A
CHEMBL224
Ki 9.33 8.8 0.5 3
5-hydroxytryptamine receptor 2A
CHEMBL322
Ki 8.64 8.64 2.3 1
5-hydroxytryptamine receptor 7
CHEMBL3155
Ki 8.43 7.975 3.7 2
D(2) dopamine receptor
CHEMBL217
EC50 8.2 7.954 6.3 5
Histamine H1 receptor
CHEMBL231
Ki 8.05 8.05 8.9 1
D(3) dopamine receptor
CHEMBL234
Ki 7.98 7.98 10.4 1
5-hydroxytryptamine receptor 1D
CHEMBL1983
Ki 7.62 7.62 24.1 1
Alpha-1A adrenergic receptor
CHEMBL229
Ki 7.53 7.53 29.3 1
D(4) dopamine receptor
CHEMBL219
Ki 7.44 7.44 36.0 1
D(1A) dopamine receptor
CHEMBL2056
Ki 7.43 7.43 37.5 1
5-hydroxytryptamine receptor 1B
CHEMBL1898
Ki 7.37 7.37 42.6 1
Alpha-1B adrenergic receptor
CHEMBL232
Ki 7.24 7.24 57.9 1
5-hydroxytryptamine receptor 2C
CHEMBL225
Ki 7.22 7.22 60.5 1
Alpha-2C adrenergic receptor
CHEMBL1916
Ki 7.22 7.22 59.9 1
Sigma intracellular receptor 2
CHEMBL4105907
Ki 7.2 7.2 63.0 1
Sodium-dependent serotonin transporter
CHEMBL228
Ki 7.18 7.18 65.5 1
Alpha-1D adrenergic receptor
CHEMBL223
Ki 7.12 7.12 76.4 1
5-hydroxytryptamine receptor 5A
CHEMBL3426
Ki 6.75 6.75 177.8 1
Alpha-2B adrenergic receptor
CHEMBL1942
Ki 6.72 6.72 191.5 1
Alpha-2A adrenergic receptor
CHEMBL1867
Ki 6.67 6.67 212.2 1
5-hydroxytryptamine receptor 6
CHEMBL3371
Ki 6.51 6.51 308.4 1
D(1B) dopamine receptor
CHEMBL1850
Ki 6.46 6.46 344.5 1
Sodium-dependent dopamine transporter
CHEMBL238
Ki 6.44 6.44 363.8 1
Sigma non-opioid intracellular receptor 1
CHEMBL287
Ki 6.34 6.34 451.5 1
5-hydroxytryptamine receptor 1E
CHEMBL2182
Ki 6.32 6.32 478.0 1
Beta-1 adrenergic receptor
CHEMBL213
Ki 6.23 6.23 589.9 1
Sodium-dependent noradrenaline transporter
CHEMBL222
Ki 6.16 6.16 689.2 1
Beta-2 adrenergic receptor
CHEMBL210
Ki 6.01 6.01 968.7 1
5-hydroxytryptamine receptor 3A
CHEMBL1899
Ki 5.82 5.82 1528.1 1
Histamine H3 receptor
CHEMBL264
Ki 5.58 5.58 2607.3 1
G-protein coupled receptor 183
CHEMBL3259470
IC50 5.44 5.44 3634.5 1
SARS-CoV-2
CHEMBL4303835
IC50 4.79 4.79 16040.0 1

Pharmacokinetic Data

Parameter Value Units Species
T1/2 0.2875 hr Mus musculus
T1/2 0.4527 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
5-hydroxytryptamine receptor 1A Ki = 0.09 nM 10.05 Displacement of [3H]-8-OH-DPAT from 5HT1A receptor in rat brain hippocampus incu... 31547945
5-hydroxytryptamine receptor 1A Ki = 0.12 nM 9.92 Displacement of [3H]-8-OH-DPAT from human 5HT1A receptor expressed in CHO-K1 cel... 31586817
5-hydroxytryptamine receptor 1A Ki = 0.12 nM 9.92 Displacement of [3H](+)8-OH-DPAT from human 5HT1A receptor expressed in human He... 32877805
D(2) dopamine receptor Ki = 0.2 nM 9.7 Dopamine D2 Receptor Binding Assay: The assay was performed according to the met... -
D(2) dopamine receptor Ki = 0.3 nM 9.52 Displacement of [3H]raclopride from human D2 long receptor expressed in CHO cell... 32877805
D(2) dopamine receptor Ki = 0.3 nM 9.52 Displacement of [3H]-raclopride from human D2L receptor expressed in HEK293 cell... 31586817
5-hydroxytryptamine receptor 2B Ki = 0.3981 nM 9.4 Binding affinity to 5-HT2BR (unknown origin) 31586817
5-hydroxytryptamine receptor 2A Ki = 0.47 nM 9.33 Displacement of [3H]ketanserin from human 5HT2A receptor expressed in CHO-K1 cel... 32877805
5-hydroxytryptamine receptor 2A Ki = 0.47 nM 9.33 Displacement of [3H]-Ketanserin from human 5-HT2A receptor expressed in rat cort... 31586817
D(2) dopamine receptor Ki = 0.51 nM 9.29 Displacement of [3H]-N-methylspiperone from D2 receptor (unknown origin) express... 34797051
D(2) dopamine receptor Ki = 0.5129 nM 9.29 Displacement of [3H]-N-methylspiperone from D2 receptor (unknown origin) express... 34797051
5-hydroxytryptamine receptor 2A Ki = 2.3 nM 8.64 Serotonin 5-HT2A Receptor Binding Assay: The assay was performed according to th... -
5-hydroxytryptamine receptor 7 Ki = 3.7 nM 8.43 Displacement of [3H]-5-CT from human 5HT7 receptor expressed in HEK293 cells inc... 31586817
D(2) dopamine receptor Ki = 3.8 nM 8.42 Displacement of [3H]raclopride from D2 receptor in rat brain striatum incubated ... 31547945
D(2) dopamine receptor Ki = 5.985 nM 8.22 PDSP Secondary Binding target: DRD2 - Compounds are tested at 10 uM concentratio... -
D(2) dopamine receptor EC50 = 6.3 nM 8.2 Agonist activity at D2 receptor (unknown origin) 32122737
Histamine H1 receptor Ki = 8.875 nM 8.05 PDSP Secondary Binding target: HRH1 - Compounds are tested at 10 uM concentratio... -
D(2) dopamine receptor EC50 = 10.0 nM 8.0 Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T ce... 34797051
D(2) dopamine receptor EC50 = 10.2 nM 7.99 Partial agonist activity at D2 receptor (unknown origin) expressed in HEK293T ce... 34797051
D(3) dopamine receptor Ki = 10.42 nM 7.98 PDSP Secondary Binding target: DRD3 - Compounds are tested at 10 uM concentratio... -

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL5724801 Fibroblast 304
- 10.6019/CHEMBL5058577 Fibroblast 304
- 10.6019/CHEMBL5724801 HEK-293T 304
- 10.6019/CHEMBL5058577 HEK-293T 304
- 10.6019/CHEMBL5724801 U2OS 304
- 10.6019/CHEMBL5058577 U2OS 304
- 10.6019/CHEMBL5058564 Fibroblast 8
34797051 10.1021/acs.jmedchem.1c01327 D(2) dopamine receptor 8
- 10.6019/CHEMBL5058564 HEK-293T 4
- 10.6019/CHEMBL4651402 SARS-CoV-2 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
- 10.6019/CHEMBL5058564 U2OS 3
- 10.6019/CHEMBL5209801 Alpha-2A adrenergic receptor 2
- 10.6019/CHEMBL4651402 Vero C1008 2
34797051 10.1021/acs.jmedchem.1c01327 ADMET 2
32122737 10.1016/j.bmcl.2020.127027 D(2) dopamine receptor 2
- 10.6019/CHEMBL4495564 Replicase polyprotein 1ab 2
- 10.21203/rs.3.rs-23951/v1 SARS-CoV-2 2
- 10.6019/CHEMBL5209801 G-protein coupled receptor 35 2
- 10.6019/CHEMBL5209801 CX3C chemokine receptor 1 2

Data from ChEMBL 36 via Core Engine