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

Details

Stereochemistry ABSOLUTE
Molecular Formula C32H31BrN2O2.C4H4O4
Molecular Weight 671.577
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of BEDAQUILINE FUMARATE

SMILES

OC(=O)\C=C\C(O)=O.COC1=NC2=CC=C(Br)C=C2C=C1[C@@H](C3=CC=CC=C3)[C@@](O)(CCN(C)C)C4=C5C=CC=CC5=CC=C4

InChI

InChIKey=ZLVSPMRFRHMMOY-WWCCMVHESA-N
InChI=1S/C32H31BrN2O2.C4H4O4/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;5-3(6)1-2-4(7)8/h4-17,20-21,30,36H,18-19H2,1-3H3;1-2H,(H,5,6)(H,7,8)/b;2-1+/t30-,32-;/m1./s1

HIDE SMILES / InChI

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
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
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.
Name Type Language
BEDAQUILINE FUMARATE
MI   ORANGE BOOK   USAN   WHO-DD  
USAN  
Official Name English
3-QUINOLINEETHANOL, 6-BROMO-.ALPHA.-(2-(DIMETHYLAMINO)ETHYL)-2-METHOXY-.ALPHA.-1-NAPHTHALENYL-.BETA.-PHENYL-, (.ALPHA.S,.BETA.R)-, (2E)-2-BUTENEDIOATE (1:1) (SALT)
Common Name English
R-403323
Code English
BEDAQUILINE FUMARATE [USAN]
Common Name English
BEDAQUILINE FUMARATE [MI]
Common Name English
SIRTURO
Brand Name English
(1R,2S)-1-(6-BROMO-2-METHOXYQUINOLIN-3-YL)-4-(DIMETHYLAMINO)-2-(NAPHTHALEN-1-YL)-1- PHENYLBUTAN-2-OL (2E)-BUT-2-ENEDIOATE SALT (1:1)
Common Name English
BEDAQUILINE FUMARATE [JAN]
Common Name English
Bedaquiline fumarate [WHO-DD]
Common Name English
R403323
Code English
BEDAQUILINE FUMARATE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C280
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
EU-Orphan Drug EU/3/05/314
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
Code System Code Type Description
USAN
XX-136
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
PRIMARY
SMS_ID
100000141480
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
PRIMARY
DRUG BANK
DBSALT000016
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
PRIMARY
PUBCHEM
24812732
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
PRIMARY
EVMPD
SUB91883
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
PRIMARY
EPA CompTox
DTXSID401004837
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
PRIMARY
ChEMBL
CHEMBL376488
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
PRIMARY
NCI_THESAURUS
C142949
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
PRIMARY
CHEBI
72295
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
PRIMARY
MERCK INDEX
m2288
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
PRIMARY Merck Index
CAS
845533-86-0
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
PRIMARY
FDA UNII
P04QX2C1A5
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
PRIMARY
DAILYMED
P04QX2C1A5
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
PRIMARY
RXCUI
1364503
Created by admin on Fri Dec 15 18:56:12 GMT 2023 , Edited by admin on Fri Dec 15 18:56:12 GMT 2023
PRIMARY RxNorm
ACTIVE MOIETY
Structure of BEDAQUILINE
PARENT (SALT/SOLVATE)
Structure of Fumaric acid
SUBSTANCE RECORD
Structure of BEDAQUILINE FUMARATE
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