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Compound Detail

CHEMBL207538

BREXANOLONE
💊 Approved Drug
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💊 Approved Drug
CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C

Basic Information

ChEMBL ID CHEMBL207538
Name BREXANOLONE
Phase Approved
Structure Type MOL
InChI Key AURFZBICLPNKBZ-SYBPFIFISA-N
Therapeutic ✓ Yes

Known Names

Allopregnan-3.alpha.-ol-20-one Allopregnanolone Allotetrahydroprogesterone Brexanolona Brexanolone SAGE-547 SGE-102 Zulresso
10
Targets
40
Activities
2
Assay Types
12
PK Parameters
20
Publications
8
Known Names
12
Indications
1
Mechanisms

Molecular Properties

318.5
MW (Da)
4.60
ALogP
2
HBA
1
HBD
37.3
PSA (Ų)
0.77
QED
0
Ro5 Violations
1
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2019
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Parenteral

Flags

Black Box Warning Natural Product First in Class
USAN Stem -olone
USAN Year 2016

Extended Properties

Molecular Formula C21H34O2
MW 318.50
Aromatic Rings 0
Heavy Atoms 23
NP-Likeness 2.21

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
GABA-A receptor; anion channel positive allosteric modulator POSITIVE ALLOSTERIC MODULATOR GABA-A receptor; anion channel

Indications

Depression, Postpartum Depressive Disorder Depressive Disorder Status Epilepticus Alzheimer Disease Brain Injuries Essential Tremor Stress Disorders, Post-Traumatic Tinnitus Alcoholism Parkinson Disease Psychotic Disorders

ATC Classification

N06AX29
brexanolone
Level 1: NERVOUS SYSTEM
Level 2: PSYCHOANALEPTICS

Drug Warnings

Black Box Warning
cardiotoxicity
Country: United States

Activity Summary

IC50 28 meas. best 7.66
EC50 12 meas. best 7.12

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
GABA-A receptor; anion channel
CHEMBL2093872
IC50 7.66 7.66 22.0 1
Unchecked
CHEMBL612545
IC50 7.66 6.889 22.0 10
GABA-A receptor; anion channel
CHEMBL1907607
IC50 7.29 6.9555 51.0 11
GABA-A receptor; agonist GABA site
CHEMBL2109244
EC50 7.12 6.87 75.5 2
Gamma-aminobutyric acid receptor subunit alpha-4/beta3/delta
CHEMBL3430899
EC50 7.12 7.12 75.5 1
GABA-A receptor; alpha-1/beta-2/gamma-2
CHEMBL2095172
EC50 6.8 6.71 160.0 2
Xenopus laevis
CHEMBL613478
EC50 6.38 5.82 420.0 6
GABA-A receptor; anion channel
CHEMBL2094133
EC50 6.06 6.06 871.0 1
Plasmodium falciparum
CHEMBL364
IC50 5.1 4.98 7943.3 5
Glucose-6-phosphate 1-dehydrogenase
CHEMBL5347
IC50 4.18 4.18 66000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 8.333 mL.min-1.kg-1 Homo sapiens
CL 55.67 mL.min-1.kg-1 Rattus norvegicus
CL 67.5 mL.min-1.kg-1 Mus musculus
CL 80.0 mL.min-1.kg-1 Rattus norvegicus
CL 8.333 mL.min-1.kg-1 Homo sapiens
CL 55.0 mL.min-1.kg-1 Rattus norvegicus
CL 66.67 mL.min-1.kg-1 Mus musculus
CL 80.0 mL.min-1.kg-1 Rattus norvegicus
CL 200.0 mL.min-1.kg-1 Mus musculus
F 2.3 % Rattus norvegicus
F 2.0 % Rattus norvegicus
F - % Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Unchecked IC50 = 22.0 nM 7.66 Displacement of [35S]TBPS from GABA-A receptor in Sprague-Dawley rat cerebral co... 28753313
GABA-A receptor; anion channel IC50 = 22.0 nM 7.66 Displacement of [3H]TBPS from GABAA receptor in Sprague-Dawley rat brain cortica... 25799373
GABA-A receptor; anion channel IC50 = 51.0 nM 7.29 Ability to allosterically modulate the binding of [35S]TBPS to gamma-aminobutyri... 9016329
Unchecked IC50 = 74.0 nM 7.13 Displacement of [35S]TBPS from rat picrotoxin binding site of GABAA receptor aft... 24328079
Unchecked IC50 = 74.0 nM 7.13 Displacement of [35S]TBPS from GABAA receptor picrotoxin binding site in rat bra... 22191644
Unchecked IC50 = 74.0 nM 7.13 Displacement of [35S]TPBS from GABAA receptor in rat brain 17434649
GABA-A receptor; anion channel IC50 = 74.0 nM 7.13 Displacement of [35S]TBPS from GABA-A receptor in rat brain membrane 16854065
GABA-A receptor; anion channel IC50 = 74.0 nM 7.13 Displacement of [35S]TBPS from picrotoxin site of GABA-A receptor of rat brain m... 15828844
GABA-A receptor; anion channel IC50 = 74.0 nM 7.13 Non-competitive displacement of [35S]TBPS from picrotoxin binding site found in ... 14640542
GABA-A receptor; anion channel IC50 = 74.0 nM 7.13 Displacement of [3S]-tert-butylbicyclophosphorothionate (TBPS) from Gamma-aminob... 10966737
Gamma-aminobutyric acid receptor subunit alpha-4/beta3/delta EC50 = 75.5 nM 7.12 Positive allosteric modulation of GABAA receptor alpha4beta3delta (unknown origi... 28753313
GABA-A receptor; agonist GABA site EC50 = 75.5 nM 7.12 Positive allosteric modulation of recombinant alpha4beta3delta GABAA receptor (u... 25799373
GABA-A receptor; anion channel IC50 = 80.0 nM 7.1 Displacement of [35S]-TBPS GABAA receptor in Wistar rat brain membrane incubated... 29223589
Unchecked IC50 = 80.0 nM 7.1 Displacement of [35S]TBPS from GABAA receptor in rat cerebellum after 60 mins 20417993
Unchecked IC50 = 80.0 nM 7.1 Inhibition of [35S]tert-butylbicyclo[ 2.2.2]phosphorothionate binding to GABAA r... 19719120
Unchecked IC50 = 80.0 nM 7.1 Displacement of [35S]TBPS from Wistar rat brain GABAA receptor 19290593
GABA-A receptor; anion channel IC50 = 80.0 nM 7.1 In vitro binding affinity to the Gamma-aminobutyric acid A receptor complex in p... 10395481
GABA-A receptor; anion channel IC50 = 86.0 nM 7.07 Displacement of [35S]-TBPS from rat synaptosomes GABAA receptor incubated for 90... 29223589
GABA-A receptor; anion channel IC50 = 91.0 nM 7.04 The concentration required to inhibit 50% of binding of [35S]TBPS to Gamma-amino... 9171876
Unchecked IC50 = 140.0 nM 6.85 Displacement of [3H]ethynylpropylbicycloorthobenzoate from GABAA receptor from r... 19497738

Literature References

PubMed DOI Target Context # Activities
19709888 10.1016/j.bmc.2009.08.008 Unchecked 16
22191644 10.1021/jm2014925 Unchecked 7
24328079 10.1021/jm401577c Unchecked 6
19734910 10.1038/nchembio.215 Plasmodium falciparum 5
14640542 10.1021/jm030302m Unchecked 5
17434649 10.1016/j.ejmech.2007.02.017 Unchecked 5
28753313 10.1021/acs.jmedchem.7b00846 ADMET 5
15828844 10.1021/jm049027+ GABA-A receptor; alpha-1/beta-2/gamma-2 4
14640542 10.1021/jm030302m GABA-A receptor; alpha-1/beta-2/gamma-2 4
10966737 10.1021/jm0002477 GABA-A receptor; alpha-1/beta-2/gamma-2 4
16854065 10.1021/jm0602920 GABA-A receptor; alpha-1/beta-2/gamma-2 4
- 10.6019/CHEMBL4495565 SARS-CoV-2 4
2160534 10.1021/jm00168a008 Rattus norvegicus 4
10395481 10.1021/jm9805889 GABA-A receptor; anion channel 3
16722640 10.1021/jm060002f Cortical neurone 3
29223589 10.1016/j.bmcl.2017.11.043 GABA-A receptor; anion channel 3
19719120 10.1021/jm900495f Unchecked 3
19497738 10.1016/j.bmcl.2009.05.065 Unchecked 3
19290593 10.1021/jm801454a Unchecked 2
12565926 10.1016/s0960-894x(02)01019-3 GABA-A receptor; anion channel 2

Data from ChEMBL 36 via Core Engine