U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C32H31BrN2O2
Molecular Weight 555.505
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BEDAQUILINE

SMILES

COC1=NC2=CC=C(Br)C=C2C=C1[C@@H](C3=CC=CC=C3)[C@@](O)(CCN(C)C)C4=CC=CC5=CC=CC=C45

InChI

InChIKey=QUIJNHUBAXPXFS-XLJNKUFUSA-N
InChI=1S/C32H31BrN2O2/c1-35(2)19-18-32(36,28-15-9-13-22-10-7-8-14-26(22)28)30(23-11-5-4-6-12-23)27-21-24-20-25(33)16-17-29(24)34-31(27)37-3/h4-17,20-21,30,36H,18-19H2,1-3H3/t30-,32-/m1/s1

HIDE SMILES / InChI
Molecular Formula C32H31BrN2O2
Molecular Weight 555.505
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Bedaquiline (trade name Sirturo, code names TMC207 and R207910) is a diarylquinoline anti-tuberculosis drug, which was discovered by a team led by Koen Andries at Janssen Pharmaceutica. When it was approved by the FDA on the 28th December 2012, it was the first new medicine to fight TB in more than forty years, and is specifically approved to treat multi-drug-resistant tuberculosis. Bedaquiline is a diarylquinoline antimycobacterial drug that inhibits the proton pump of mycobacterial ATP (adenosine 5'-triphosphate) synthase, an enzyme that is essential for the generation of energy in Mycobacterium tuberculosis. Bacterial death occurs as a result of bedaquiline.

Originator

Approval Year

2012
595
Targets

Targets

Primary TargetPharmacologyConditionPotency
ATP synthase subunit c
2
Target ID: P9WPS0
Gene ID: NA
Gene Symbol: atpE
Target Organism: Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)
Inhibitor
8297
ATP synthase subunit c
2
Target ID: P9WPS1
Gene ID: 886937.0
Gene Symbol: atpE
Target Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Inhibitor
8297
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Approved
8429
SIRTURO

Approved Use

Indicated as part of combination therapy in the treatment of adults (18 years and older) with pulmonary multi-drug resistant tuberculosis (MDR-TB). Reserve SIRTURO for use when an effective treatment regimen cannot otherwise be provided. Administer SIRTURO by directly observed therapy (DOT). This indication is approved under accelerated approval based on time to sputum culture conversion

Launch Date

2012
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.547 mg/L
REVIEW
https://pubmed.ncbi.nlm.nih.gov/24860154/
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BEDAQUILINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3.755 mg/L
REVIEW
https://pubmed.ncbi.nlm.nih.gov/24860154/
450 mg single, oral
dose: 450 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BEDAQUILINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
38.737 mg × h/L
REVIEW
https://pubmed.ncbi.nlm.nih.gov/24860154/
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BEDAQUILINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
64.53 mg × h/mL
REVIEW
https://pubmed.ncbi.nlm.nih.gov/24860154/
450 mg single, oral
dose: 450 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BEDAQUILINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
24 h
REVIEW
https://pubmed.ncbi.nlm.nih.gov/24860154/
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BEDAQUILINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
24 h
REVIEW
https://pubmed.ncbi.nlm.nih.gov/24860154/
450 mg single, oral
dose: 450 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BEDAQUILINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.01%
REVIEW
https://pubmed.ncbi.nlm.nih.gov/24860154/
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BEDAQUILINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
0.01%
REVIEW
https://pubmed.ncbi.nlm.nih.gov/24860154/
450 mg single, oral
dose: 450 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BEDAQUILINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
0.01%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/204384s000lbl.pdf
400 mg 1 times / day unknown, oral
dose: 400 mg
route of administration: Oral
experiment type: UNKNOWN
co-administered:
BEDAQUILINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
400 mg 4 times / week multiple, oral
Overdose
Dose: 400 mg, 4 times / week
Route: oral
Route: multiple
Dose: 400 mg, 4 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/30951878
unhealthy, 21 years
n = 1
Health Status: unhealthy
Age Group: 21 years
Sex: M
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/30951878
Sources:
https://pubmed.ncbi.nlm.nih.gov/30951878
400 | 200 mg|mg 1|3 times / day|week multiple, oral (complex)
Recommended
Dose: 400 | 200 mg|mg, 1|3 times / day|week
Route: oral
Route: multiple
Dose: 400 | 200 mg|mg, 1|3 times / day|week
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/204384s000lbl.pdf
unhealthy, 34 years
n = 79
Health Status: unhealthy
Condition: y multi-drug resistant tuberculosis
Age Group: 34 years
Sex: M+F
Population Size: 79
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/204384s000lbl.pdf
Other AEs: Death...
Other AEs:
Death (11.4%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/204384s000lbl.pdf
AEs

AEs

AESignificanceDosePopulation
Death 11.4%
400 | 200 mg|mg 1|3 times / day|week multiple, oral (complex)
Recommended
Dose: 400 | 200 mg|mg, 1|3 times / day|week
Route: oral
Route: multiple
Dose: 400 | 200 mg|mg, 1|3 times / day|week
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/204384s000lbl.pdf
unhealthy, 34 years
n = 79
Health Status: unhealthy
Condition: y multi-drug resistant tuberculosis
Age Group: 34 years
Sex: M+F
Population Size: 79
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/204384s000lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

inhibitor
1587

inducer
781
inhibitor
1767

inducer
389
inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1524

CYP2A6
707

CYP2C8
911

CYP2C19
1478

CYP2E1
882

CYP3A4/5
278

CYP4A
19

P-gp
1461
P-gp
1537
CYP1A2
701

CYP2C19
293
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1692
 no
CYP1A2
1692
 no
CYP2A6
739
 no
CYP2C19
1553
 no
CYP2C19
1553
 no
CYP2C8
965
 no
CYP2C9
1819
 no
CYP2C9
1819
 no
CYP2D6
1891
 no
CYP2E1
970
 no
CYP3A4
1925
 no
CYP3A4
1925
 no
CYP3A4/5
335
 no
CYP4A
33
 no
P-gp
1650
 no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1737
 major
yes (co-administration study)
Comment: ketoconazole increased bedaquiline exposure 22%, rifampin decreased bedaquiline exposure 52%
Page: 5.0
P-gp
1537
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:72292
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:72292
MolPort
MolPort-035-683-920
https://www.molport.com/shop/molecule-link/MolPort-035-683-920
ZINC
ZINC000004655029
http://zinc15.docking.org/substances/ZINC000004655029
PubMed

PubMed

TitleDatePubMed
New small-molecule synthetic antimycobacterials.
2005 Jun
TMC207: the first compound of a new class of potent anti-tuberculosis drugs.
2010 Jun
Bactericidal activity of the diarylquinoline TMC207 against Mycobacterium tuberculosis outside and within cells.
2010 Sep
Patents

Patents

08039628
2
08350040
2
20050148581
2
20060281741
2

Sample Use Guides

In Vivo Use Guide
400 mg once daily for 2 weeks followed by 200 mg 3 times per week for 22 weeks with food. Swallow SIRTURO (bedaquiline) tablets whole with water.
Route of Administration: Oral
In Vitro Use Guide
Modification of the atpE target gene, and/or upregulation of the MmpS5-MmpL5 efflux pump have been associated with increased bedaquiline MIC values in isolates of M. tuberculosis. Target-based mutations generated in preclinical studies lead to 8- to 133-fold increases in bedaquiline MIC, resulting in MICs ranging from 0.25 to 4.0 ug/mL. Efflux-based mutations have been seen in preclinical and clinical isolates. These lead to 2- to 8-fold increases in bedaquiline MICs, resulting in bedaquiline MICs ranging from 0.25 to 0.50 ug/ mL.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:23:58 GMT 2023
Edited
by admin
on Fri Dec 15 16:23:58 GMT 2023
Record UNII
78846I289Y
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BEDAQUILINE
DASH   INN   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
bedaquiline [INN]
Common Name English
(1R,2S) 6-BROMO-ALPHA-(2-(DIMETHYLAMINO)ETHYL)-2-METHOXY-ALPHA-(1-NAPHTHYL)-BETA-PHENYL-3-QUINOLINEETHANOL
Systematic Name English
BEDAQUILINE [VANDF]
Common Name English
TMC207
Code English
BEDAQUILINE [USAN]
Common Name English
(1R,2S)-1-(6-BROMO-2-METHOXYQUINOLIN-3-YL)-4-(DIMETHYLAMINO)-2-(NAPHTHALEN-1-YL)-1- PHENYLBUTAN-2-OL
Systematic Name English
3-QUINOLINEETHANOL, 6-BROMO-.ALPHA.-(2-(DIMETHYLAMINO)ETHYL)-2-METHOXY-.ALPHA.-1-NAPHTHALENYL-.BETA.-PHENYL-, (.ALPHA.S,.BETA.R)-
Common Name English
R-207910
Code English
TMC-207
Code English
BEDAQUILINE [MI]
Common Name English
R207910
Code English
Bedaquiline [WHO-DD]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 589917
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
NDF-RT N0000186775
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
WHO-VATC QJ04AK05
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
NCI_THESAURUS C280
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
WHO-ATC J04AK05
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
FDA ORPHAN DRUG 199304
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
LIVERTOX NBK548859
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
Code System Code Type Description
ChEMBL
CHEMBL376488
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
USAN
XX-135
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
SMS_ID
100000126166
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
DAILYMED
78846I289Y
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
MERCK INDEX
m2288
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY Merck Index
EPA CompTox
DTXSID80903989
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
WIKIPEDIA
Bedaquiline
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
EVMPD
SUB32824
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
DRUG BANK
DB08903
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
PUBCHEM
5388906
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
DRUG CENTRAL
4741
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
NCI_THESAURUS
C87658
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
RXCUI
1364504
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY RxNorm
HSDB
8217
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
EU-Orphan Drug
EU/3/05/314 POSITIVE
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY On 26 August 2005, orphan designation (EU/3/05/314) was granted by the European Commission to Tibotec Pharmaceuticals Ltd., Ireland, for (1R,2S)  6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(1-naphthyl)-beta-phenyl-3-quinolineethanol for the treatment of tuberculosis.
LACTMED
Bedaquiline
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
CHEBI
72292
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
NDF-RT
N0000186774
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY Diarylquinolines [Chemical/Ingredient]
INN
9316
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
CAS
843663-66-1
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
FDA UNII
78846I289Y
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
MESH
C493870
Created by admin on Fri Dec 15 16:23:58 GMT 2023 , Edited by admin on Fri Dec 15 16:23:58 GMT 2023
PRIMARY
Related Record Type Details
POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY H MEMBER 2
OFF-TARGET->INHIBITOR
IC50
Structure of BEDAQUILINE
EXCRETED UNCHANGED
FECAL
Structure of BEDAQUILINE FUMARATE
SALT/SOLVATE -> PARENT
MYCOBACTERIUM TUBERCULOSIS
TARGET ORGANISM->INHIBITOR
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
Related Record Type Details
Structure of N-MONODESMETHYL BEDAQUILINE
METABOLITE LESS ACTIVE -> PARENT
CYP3A4 METABOLITE; 4-5 TIMES LESS ACTIVE; RESPONSIBLE FOR QT PROLONGATION DUE TO LONG TERMINAL HALF LIFE
MAJOR
FECAL
Related Record Type Details
Structure of BEDAQUILINE
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966