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

Details

Stereochemistry ABSOLUTE
Molecular Formula C32H31BrN2O2
Molecular Weight 555.5055
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BEDAQUILINE

SMILES

CN(C)CC[C@@](c1cccc2ccccc21)([C@]([H])(c3ccccc3)c4cc5cc(ccc5nc4OC)Br)O

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
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

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P9WPS0
Gene ID: NA
Gene Symbol: atpE
Target Organism: Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)
Target ID: P9WPS1
Gene ID: 886937.0
Gene Symbol: atpE
Target Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
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

1.35665274E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.547 mg/L
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
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
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
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
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
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%
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%
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%
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:
unhealthy, 21 years
n = 1
Health Status: unhealthy
Age Group: 21 years
Sex: M
Population Size: 1
Sources:
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:
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:
Other AEs: Death...
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:
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:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
Drug as victim

Drug as victim

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

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
In vitro interactions between new antitubercular drug candidates SQ109 and TMC207.
2010 Jul
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
Short-course chemotherapy with TMC207 and rifapentine in a murine model of latent tuberculosis infection.
2011 Sep 15
Efflux inhibition with verapamil potentiates bedaquiline in Mycobacterium tuberculosis.
2014
Patents

Sample Use Guides

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
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.
Name Type Language
BEDAQUILINE
DASH   INN   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
BEDAQUILINE [INN]
Common Name English
BEDAQUILINE [WHO-DD]
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
Classification Tree Code System Code
FDA ORPHAN DRUG 589917
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
NDF-RT N0000186775
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
WHO-VATC QJ04AK05
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
NCI_THESAURUS C280
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
WHO-ATC J04AK05
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
FDA ORPHAN DRUG 199304
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
LIVERTOX 90
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL376488
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY
MERCK INDEX
M2288
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY Merck Index
WIKIPEDIA
Bedaquiline
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY
EVMPD
SUB32824
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY
DRUG BANK
DB08903
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY
PUBCHEM
5388906
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY
DRUG CENTRAL
4741
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY
NCI_THESAURUS
C87658
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY
RXCUI
1364504
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY RxNorm
HSDB
8217
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY
EU-Orphan Drug
EU/3/05/314 POSITIVE
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
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 Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY
NDF-RT
N0000186774
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY Diarylquinolines [Chemical/Ingredient]
INN
9316
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY
CAS
843663-66-1
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY
FDA UNII
78846I289Y
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY
MESH
C493870
Created by admin on Sat Jun 26 04:38:50 UTC 2021 , Edited by admin on Sat Jun 26 04:38:50 UTC 2021
PRIMARY