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Compound Detail

CHEMBL376488

BEDAQUILINE
💊 Approved Drug
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💊 Approved Drug
COc1nc2ccc(Br)cc2cc1[C@@H](c1ccccc1)[C@@](O)(CCN(C)C)c1cccc2ccccc12

Basic Information

ChEMBL ID CHEMBL376488
Name BEDAQUILINE
Phase Approved
Structure Type MOL
InChI Key QUIJNHUBAXPXFS-XLJNKUFUSA-N
Therapeutic ✓ Yes

Known Names

Bedaquilina Bedaquiline R-207910 R207910 TMC-207 TMC207
7
Targets
31
Activities
3
Assay Types
30
PK Parameters
20
Publications
6
Known Names
8
Indications

Molecular Properties

555.5
MW (Da)
7.13
ALogP
4
HBA
1
HBD
45.6
PSA (Ų)
0.22
QED
2
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2012
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Black Box Warning Natural Product First in Class
USAN Stem -quiline
USAN Year 2010

Extended Properties

Molecular Formula C32H31BrN2O2
MW 555.52
Aromatic Rings 5
Heavy Atoms 37
NP-Likeness -0.55

Indications

Tuberculosis Leprosy Tuberculosis, Multidrug-Resistant Tuberculosis, Multidrug-Resistant Tuberculosis, Pulmonary Lung Diseases Mycobacterium avium-intracellulare Infection Liver Diseases

ATC Classification

J04AK05
bedaquiline
Level 1: ANTIINFECTIVES FOR SYSTEMIC USE
Level 2: ANTIMYCOBACTERIALS

Activity Summary

IC50 28 meas. best 9.0
Kd 2 meas. best 6.3
EC50 1 meas. best 4.82

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Mycolicibacterium smegmatis
CHEMBL613088
IC50 9.0 9.0 1.0 1
Putative uncharacterized protein atpE
CHEMBL1641346
IC50 8.6 8.05 2.5 4
Unchecked
CHEMBL612545
IC50 8.3 5.605 5.0 10
Mycobacterium tuberculosis
CHEMBL360
IC50 7.47 7.385 34.0 2
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 6.43 5.9611 370.0 9
ATP synthase subunit c
CHEMBL3308989
Kd 6.3 6.3 500.0 1
Unchecked
CHEMBL612545
Kd 5.82 5.82 1500.0 1
Replicase polyprotein 1ab
CHEMBL4523582
IC50 5.36 5.36 4360.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
EC50 4.82 4.82 15000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 3973.0 ng.hr.mL-1 Homo sapiens
AUC 16050.0 ng.hr.mL-1 Homo sapiens
AUC 64750.0 ng.hr.mL-1 Homo sapiens
AUC 52000.0 ng.hr.mL-1 Homo sapiens
AUC 24000.0 ng.hr.mL-1 Homo sapiens
AUC 7900.0 ng.hr.mL-1 Homo sapiens
AUC 20900.0 ng.hr.mL-1 Mus musculus
AUC 20900.0 ng.hr.mL-1 Mus musculus
AUC 17400.0 ng.hr.mL-1 Mus musculus
AUC 6038.0 ng.hr.mL-1 Mus musculus
AUC 2614.0 ng.hr.mL-1 Rattus norvegicus
AUC 60551.68 ng.hr.mL-1 Rattus norvegicus
AUC 21000.0 ng.hr.mL-1 Mus musculus
CL 14.13 uL.min-1.(10^6cells)-1 Rattus norvegicus
CL 19.95 mL.min-1.g-1 Homo sapiens
CL 3.0 mL.min-1.g-1 Homo sapiens
CL 3.0 mL.min-1.g-1 Homo sapiens
CL 3.0 mL.min-1.g-1 Homo sapiens
CL 7.3 mL.min-1.g-1 Mus musculus
CL 7.0 mL.min-1.kg-1 Mus musculus
CL 7.0 mL.min-1.kg-1 Mus musculus
CL 7.0 mL.min-1.kg-1 Mus musculus
CL 0.003 mL.min-1.kg-1 Homo sapiens
CL 0.007 mL.min-1.kg-1 Mus musculus
CL 34.1 mL.min-1.g-1 Homo sapiens
CL 87.8 mL.min-1.g-1 Rattus norvegicus
CL 183.0 mL.min-1.g-1 Mus musculus
CL 7.76 mL.min-1.kg-1 Mus musculus
CL 8.67 mL.min-1.kg-1 Rattus norvegicus
CL 3.0 mL.min-1.g-1 Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Mycolicibacterium smegmatis IC50 = 1.0 nM 9.0 Inhibition of oxidative phosphorylation in Mycobacterium smegmatis membrane vesi... 25221657
Putative uncharacterized protein atpE IC50 = 2.5 nM 8.6 Inhibition of Mycobacterium smegmatis ATCC 607 ATP synthase subunit c-mediated A... 17496888
Unchecked IC50 = 5.0 nM 8.3 Inhibition of ATP synthase in Mycobacterium smegmatis inverted membrane vesicles... -
Putative uncharacterized protein atpE IC50 = 10.0 nM 8.0 Inhibition of Mycobacterium smegmatis MC2 155 ATP synthase subunit c-mediated AT... 19075053
Putative uncharacterized protein atpE IC50 = 10.0 nM 8.0 Inhibition of Mycobacterium smegmatis MC2 155 ATP synthase subunit c-mediated AT... 19075053
Unchecked IC50 = 10.0 nM 8.0 Inhibition of Mycobacterium smegmatis ATP synthase 34963068
Unchecked IC50 = 20.0 nM 7.7 Inhibition of Mycobacterium phlei DSM-43239 C-terminal ATP-synthase assessed as ... 31664826
Putative uncharacterized protein atpE IC50 = 25.0 nM 7.6 Inhibition of Mycobacterium smegmatis ATCC 607 ATP synthase subunit c-mediated A... 17496888
Mycobacterium tuberculosis IC50 = 34.0 nM 7.47 Antimycobacterial activity against Mycobacterium tuberculosis H37Rv infected in ... 36473699
Mycobacterium tuberculosis IC50 = 50.0 nM 7.3 Antimycobacterial activity against Mycobacterium tuberculosis H37Rv expressing L... 25818768
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 370.0 nM 6.43 Inhibition of human ERG 29107541
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 370.0 nM 6.43 Inhibition of human ERG assessed as prolongation of QT interval 29482950
ATP synthase subunit c Kd = 500.0 nM 6.3 Binding affinity to Bacillus PS3 ATP synthase subunit c 17496888
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 1036.0 nM 5.99 Inhibition of human ERG expressed in HEK293 cells by whole cell manual patch cla... 39166949
Unchecked Kd = 1500.0 nM 5.82 Binding affinity to Bacillus PS3 ATP synthase subunit c A63P mutant 17496888
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 1600.0 nM 5.8 Inhibition of human ERG by patch clamp assay 29482950
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 1600.0 nM 5.8 Inhibition of human ERG by manual patch clamp electrophysiology assay 30792104
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 1600.0 nM 5.8 Inhibition of human ERG 30803745
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 1600.0 nM 5.8 Inhibition of human ERG 31810890
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 1600.0 nM 5.8 Inhibition of human ERG 36804747

Literature References

PubMed DOI Target Context # Activities
37736177 10.1021/acsmedchemlett.3c00295 Mycobacterium tuberculosis 62
19596891 10.1128/aac.00722-09 Mycobacterium leprae 31
20038615 10.1128/aac.01611-09 Mycobacterium tuberculosis 30
35636648 10.1016/j.bmcl.2022.128824 ADMET 29
18505852 10.1128/aac.01204-07 Mycobacterium tuberculosis 28
18505852 10.1128/aac.01204-07 Homo sapiens 26
- 10.1039/C5MD00589B Mycobacterium tuberculosis 18
17496888 10.1038/nchembio884 Mycobacterium tuberculosis 15
17496888 10.1038/nchembio884 Mycolicibacterium smegmatis 14
17709466 10.1128/aac.00181-07 Mycobacterium avium 10
19075053 10.1128/aac.01393-08 Unchecked 10
35636648 10.1016/j.bmcl.2022.128824 Mycobacterium tuberculosis 9
24871036 10.1021/jm5005978 Mycobacterium tuberculosis 8
30803745 10.1016/j.bmc.2019.02.026 ADMET 8
30792104 10.1016/j.bmc.2019.02.025 ADMET 7
31810890 10.1016/j.bmc.2019.115213 ADMET 7
19738016 10.1128/aac.00689-09 Mycobacterium avium 7
28968083 10.1021/acs.jmedchem.7b01332 Mycobacterium tuberculosis 6
17709466 10.1128/aac.00181-07 Mycobacterium tuberculosis 6
24967731 10.1021/jm500833f Mycobacterium tuberculosis 6

Data from ChEMBL 36 via Core Engine