Identification

Name
Bedaquiline
Accession Number
DB08903
Type
Small Molecule
Groups
Approved
Description

Bedaquiline is a bactericidal antimycobacterial drug. Chemically it is a diarylquinoline. FDA approved on December 28, 2012.

Structure
Thumb
Synonyms
  • 1-(6-Bromo-2-methoxy-quinolin-3-yl)-4-dimethylamino-2-naphthalen-1-yl-1-phenyl-butan-2-ol
  • Bedaquilina
  • Bedaquilinum
  • R 207910
  • TMC 207
  • TMC-207
  • TMC207
External IDs
AIDS222089 / R-207910 / R207910 / TMC207
Product Ingredients
IngredientUNIICASInChI Key
Bedaquiline FumarateP04QX2C1A5845533-86-0ZLVSPMRFRHMMOY-WWCCMVHESA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SirturoTablet100 mgOralJanssen Cilag International Nv2014-03-05Not applicableEu
SirturoTablet100 mgOralJanssen Cilag International Nv2014-03-05Not applicableEu
SirturoTablet100 mg/1OralJanssen, Lp2012-12-28Not applicableUs
Categories
UNII
78846I289Y
CAS number
843663-66-1
Weight
Average: 555.505
Monoisotopic: 554.156890893
Chemical Formula
C32H31BrN2O2
InChI Key
QUIJNHUBAXPXFS-XLJNKUFUSA-N
InChI
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
IUPAC Name
(1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-(dimethylamino)-2-(naphthalen-1-yl)-1-phenylbutan-2-ol
SMILES
COC1=NC2=C(C=C(Br)C=C2)C=C1[[email protected]@H](C1=CC=CC=C1)[[email protected]@](O)(CCN(C)C)C1=CC=CC2=C1C=CC=C2

Pharmacology

Indication

Bedaquiline is indicated as part of combination therapy in adults (≥ 18 years) with pulmonary multi-drug resistant tuberculosis (MDR-TB).

Structured Indications
Pharmacodynamics

Bedaquiline is primarily subjected to oxidative metabolism leading to the formation of N-monodesmethyl metabolite (M2). M2 is not thought to contribute significantly to clinical efficacy given its lower average exposure (23% to 31%) in humans and lower antimycobacterial activity (4 to 6-fold lower) compared to the parent compound. M2 concentrations appeared to correlate with QT prolongation. Bedaquiline inhibits mycobacterial TB at a minimal inhibitory concentration (MIC) from 0.002-0.06 μg/ml and with a MIC50 of 0.03 μg/ml. Furthermore, bacteria that have smaller ATP stores (usually in dormant, nonreplicating bacilli) are more susceptible to bedaquiline.

Mechanism of action

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.

TargetActionsOrganism
AATP synthase subunit c
inhibitor
Mycobacterium tuberculosis
Absorption

Tmax, oral dose = 5 hours; Food increases the oral bioavailability. AUC increases proportionally up to the highest dose studied in healthy volunteers. When 400 mg of bedaquiline is administered once daily for a week, the peak plasma concentration (Cmax) is 5.5 μg/ml and an AUC of 64.75 μgh/ml.

Volume of distribution

Vd, central compartment = 164 L

Protein binding

>99.9 bound to plasma proteins.

Metabolism

Bedaquiline is hepatically metabolized. The main enzyme involved is CYP3A4 which metabolizes bedaquiline into the N-monodesmethyl metabolite (M2). This metabolite is 4 to 6-times less active in terms of antimycobacterial potency.

Route of elimination

Bedaquiline is primarily elimination in the feces. The urinary excretion of unchanged bedaquiline was < 0.001% of the dose in clinical studies, indicating that renal clearance of unchanged drug is insignificant.

Half life

Terminal elimination half-life, bedaquiline and M2 = 5.5 months. This long half-life suggests slow release of bedaquiline and M2 from peripheral tissues.

Clearance
Not Available
Toxicity

The most common adverse reactions reported in ≥10% of patients treated with bedaquiline are nausea, arthralgia, and headache.

Affected organisms
  • Mycobacterium tuberculosis
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AlfuzosinAlfuzosin may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
AmantadineAmantadine may increase the QTc-prolonging activities of Bedaquiline.Approved
AmiodaroneThe serum concentration of Bedaquiline can be increased when it is combined with Amiodarone.Approved, Investigational
AmitriptylineAmitriptyline may increase the QTc-prolonging activities of Bedaquiline.Approved
AmoxapineAmoxapine may increase the QTc-prolonging activities of Bedaquiline.Approved
AnagrelideBedaquiline may increase the QTc-prolonging activities of Anagrelide.Approved
ApomorphineApomorphine may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
AprepitantThe serum concentration of Bedaquiline can be increased when it is combined with Aprepitant.Approved, Investigational
ArformoterolArformoterol may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
AripiprazoleAripiprazole may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
Arsenic trioxideBedaquiline may increase the QTc-prolonging activities of Arsenic trioxide.Approved, Investigational
ArtemetherBedaquiline may increase the QTc-prolonging activities of Artemether.Approved
AsenapineBedaquiline may increase the QTc-prolonging activities of Asenapine.Approved
AtazanavirThe serum concentration of Bedaquiline can be increased when it is combined with Atazanavir.Approved, Investigational
AtomoxetineAtomoxetine may increase the QTc-prolonging activities of Bedaquiline.Approved
AzithromycinAzithromycin may increase the QTc-prolonging activities of Bedaquiline.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Bedaquiline.Investigational
BoceprevirThe serum concentration of Bedaquiline can be increased when it is combined with Boceprevir.Approved, Withdrawn
BortezomibBortezomib may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
BosentanThe serum concentration of Bedaquiline can be decreased when it is combined with Bosentan.Approved, Investigational
BuserelinBuserelin may increase the QTc-prolonging activities of Bedaquiline.Approved
CarbamazepineThe serum concentration of Bedaquiline can be decreased when it is combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Bedaquiline can be increased when it is combined with Ceritinib.Approved
ChloroquineChloroquine may increase the QTc-prolonging activities of Bedaquiline.Approved, Vet Approved
ChlorpromazineChlorpromazine may increase the QTc-prolonging activities of Bedaquiline.Approved, Vet Approved
CiprofloxacinCiprofloxacin may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
CisaprideBedaquiline may increase the QTc-prolonging activities of Cisapride.Approved, Investigational, Withdrawn
CitalopramBedaquiline may increase the QTc-prolonging activities of Citalopram.Approved
ClarithromycinThe serum concentration of Bedaquiline can be increased when it is combined with Clarithromycin.Approved
ClemastineThe metabolism of Bedaquiline can be decreased when combined with Clemastine.Approved
ClomipramineClomipramine may increase the QTc-prolonging activities of Bedaquiline.Approved, Vet Approved
ClotrimazoleThe metabolism of Bedaquiline can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineClozapine may increase the QTc-prolonging activities of Bedaquiline.Approved
CobicistatThe serum concentration of Bedaquiline can be increased when it is combined with Cobicistat.Approved
ConivaptanThe serum concentration of Bedaquiline can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibCrizotinib may increase the QTc-prolonging activities of Bedaquiline.Approved
CyclosporineThe metabolism of Bedaquiline can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Bedaquiline can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe serum concentration of Bedaquiline can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Bedaquiline can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Bedaquiline can be decreased when it is combined with Deferasirox.Approved, Investigational
DegarelixDegarelix may increase the QTc-prolonging activities of Bedaquiline.Approved
DelavirdineThe metabolism of Bedaquiline can be decreased when combined with Delavirdine.Approved
DesfluraneDesflurane may increase the QTc-prolonging activities of Bedaquiline.Approved
DesipramineDesipramine may increase the QTc-prolonging activities of Bedaquiline.Approved
DihydroergotamineThe metabolism of Bedaquiline can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Bedaquiline can be decreased when combined with Diltiazem.Approved
DiphenhydramineDiphenhydramine may increase the QTc-prolonging activities of Bedaquiline.Approved
DisopyramideBedaquiline may increase the QTc-prolonging activities of Disopyramide.Approved
DofetilideBedaquiline may increase the QTc-prolonging activities of Dofetilide.Approved
DolasetronDolasetron may increase the QTc-prolonging activities of Bedaquiline.Approved
DomperidoneBedaquiline may increase the QTc-prolonging activities of Domperidone.Approved, Investigational, Vet Approved
DoxepinDoxepin may increase the QTc-prolonging activities of Bedaquiline.Approved
DoxycyclineThe metabolism of Bedaquiline can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Bedaquiline can be decreased when combined with Dronedarone.Approved
DroperidolDroperidol may increase the QTc-prolonging activities of Bedaquiline.Approved, Vet Approved
EliglustatBedaquiline may increase the QTc-prolonging activities of Eliglustat.Approved
EnzalutamideThe serum concentration of Bedaquiline can be decreased when it is combined with Enzalutamide.Approved
EribulinEribulin may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
ErythromycinErythromycin may increase the QTc-prolonging activities of Bedaquiline.Approved, Vet Approved
EscitalopramBedaquiline may increase the QTc-prolonging activities of Escitalopram.Approved, Investigational
EthanolEthanol may increase the hepatotoxic activities of Bedaquiline.Approved
EzogabineEzogabine may increase the QTc-prolonging activities of Bedaquiline.Approved
FamotidineFamotidine may increase the QTc-prolonging activities of Bedaquiline.Approved
FelbamateFelbamate may increase the QTc-prolonging activities of Bedaquiline.Approved
FingolimodFingolimod may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
FlecainideFlecainide may increase the QTc-prolonging activities of Bedaquiline.Approved, Withdrawn
FluconazoleFluconazole may increase the QTc-prolonging activities of Bedaquiline.Approved
FluoxetineBedaquiline may increase the QTc-prolonging activities of Fluoxetine.Approved, Vet Approved
FlupentixolBedaquiline may increase the QTc-prolonging activities of Flupentixol.Approved, Withdrawn
FluvoxamineThe metabolism of Bedaquiline can be decreased when combined with Fluvoxamine.Approved, Investigational
FormoterolFormoterol may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
FosamprenavirThe metabolism of Bedaquiline can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Bedaquiline can be increased when it is combined with Fosaprepitant.Approved
FoscarnetFoscarnet may increase the QTc-prolonging activities of Bedaquiline.Approved
FosphenytoinThe serum concentration of Bedaquiline can be decreased when it is combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Bedaquiline can be increased when it is combined with Fusidic Acid.Approved
Gadobenic acidGadobenic acid may increase the QTc-prolonging activities of Bedaquiline.Approved
GalantamineGalantamine may increase the QTc-prolonging activities of Bedaquiline.Approved
GemifloxacinGemifloxacin may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
GoserelinGoserelin may increase the QTc-prolonging activities of Bedaquiline.Approved
GranisetronGranisetron may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
HaloperidolHaloperidol may increase the QTc-prolonging activities of Bedaquiline.Approved
HistrelinHistrelin may increase the QTc-prolonging activities of Bedaquiline.Approved
HydroxyzineHydroxyzine may increase the QTc-prolonging activities of Bedaquiline.Approved
IbandronateIbandronate may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
IbutilideBedaquiline may increase the QTc-prolonging activities of Ibutilide.Approved
IdelalisibThe serum concentration of Bedaquiline can be increased when it is combined with Idelalisib.Approved
IloperidoneBedaquiline may increase the QTc-prolonging activities of Iloperidone.Approved
ImatinibThe metabolism of Bedaquiline can be decreased when combined with Imatinib.Approved
ImipramineImipramine may increase the QTc-prolonging activities of Bedaquiline.Approved
IndacaterolIndacaterol may increase the QTc-prolonging activities of Bedaquiline.Approved
IndapamideIndapamide may increase the QTc-prolonging activities of Bedaquiline.Approved
IndinavirThe serum concentration of Bedaquiline can be increased when it is combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Bedaquiline can be decreased when combined with Isavuconazonium.Approved, Investigational
IsofluraneIsoflurane may increase the QTc-prolonging activities of Bedaquiline.Approved, Vet Approved
IsradipineIsradipine may increase the QTc-prolonging activities of Bedaquiline.Approved
ItraconazoleThe serum concentration of Bedaquiline can be increased when it is combined with Itraconazole.Approved, Investigational
IvabradineIvabradine may increase the QTc-prolonging activities of Bedaquiline.Approved
IvacaftorThe serum concentration of Bedaquiline can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe serum concentration of Bedaquiline can be increased when it is combined with Ketoconazole.Approved, Investigational
LapatinibLapatinib may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
LenvatinibBedaquiline may increase the QTc-prolonging activities of Lenvatinib.Approved
LeuprolideLeuprolide may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
LevofloxacinLevofloxacin may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
LithiumLithium may increase the QTc-prolonging activities of Bedaquiline.Approved
LopinavirThe serum concentration of Bedaquiline can be increased when it is combined with Lopinavir.Approved
LovastatinThe metabolism of Bedaquiline can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Bedaquiline can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Bedaquiline can be decreased when it is combined with Lumacaftor.Approved
LumefantrineBedaquiline may increase the QTc-prolonging activities of Lumefantrine.Approved
MaprotilineMaprotiline may increase the QTc-prolonging activities of Bedaquiline.Approved
MefloquineMefloquine may increase the QTc-prolonging activities of Bedaquiline.Approved
MethadoneMethadone may increase the QTc-prolonging activities of Bedaquiline.Approved
MethotrimeprazineMethotrimeprazine may increase the QTc-prolonging activities of Bedaquiline.Approved
MetoclopramideMetoclopramide may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
MetronidazoleMetronidazole may increase the QTc-prolonging activities of Bedaquiline.Approved
MifepristoneThe serum concentration of Bedaquiline can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronMirabegron may increase the QTc-prolonging activities of Bedaquiline.Approved
MirtazapineMirtazapine may increase the QTc-prolonging activities of Bedaquiline.Approved
MitotaneThe serum concentration of Bedaquiline can be decreased when it is combined with Mitotane.Approved
MoexiprilMoexipril may increase the QTc-prolonging activities of Bedaquiline.Approved
MoxifloxacinMoxifloxacin may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
NefazodoneThe serum concentration of Bedaquiline can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Bedaquiline can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Bedaquiline can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Bedaquiline can be decreased when it is combined with Nevirapine.Approved
NicardipineNicardipine may increase the QTc-prolonging activities of Bedaquiline.Approved
NilotinibThe metabolism of Bedaquiline can be decreased when combined with Nilotinib.Approved, Investigational
NorfloxacinNorfloxacin may increase the QTc-prolonging activities of Bedaquiline.Approved
NortriptylineNortriptyline may increase the QTc-prolonging activities of Bedaquiline.Approved
OctreotideOctreotide may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
OfloxacinOfloxacin may increase the QTc-prolonging activities of Bedaquiline.Approved
OlanzapineOlanzapine may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
OlaparibThe metabolism of Bedaquiline can be decreased when combined with Olaparib.Approved
OlodaterolOlodaterol may increase the QTc-prolonging activities of Bedaquiline.Approved
OndansetronOndansetron may increase the QTc-prolonging activities of Bedaquiline.Approved
OsimertinibThe serum concentration of Bedaquiline can be increased when it is combined with Osimertinib.Approved
OxytocinOxytocin may increase the QTc-prolonging activities of Bedaquiline.Approved, Vet Approved
PalbociclibThe serum concentration of Bedaquiline can be increased when it is combined with Palbociclib.Approved
PaliperidoneBedaquiline may increase the QTc-prolonging activities of Paliperidone.Approved
PanobinostatPanobinostat may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
ParoxetineParoxetine may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
PasireotidePasireotide may increase the QTc-prolonging activities of Bedaquiline.Approved
PazopanibPazopanib may increase the QTc-prolonging activities of Bedaquiline.Approved
PentamidinePentamidine may increase the QTc-prolonging activities of Bedaquiline.Approved
PentobarbitalThe serum concentration of Bedaquiline can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PerflutrenPerflutren may increase the QTc-prolonging activities of Bedaquiline.Approved
PhenobarbitalThe serum concentration of Bedaquiline can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Bedaquiline can be decreased when it is combined with Phenytoin.Approved, Vet Approved
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Bedaquiline.Approved
PimozideBedaquiline may increase the QTc-prolonging activities of Pimozide.Approved
PosaconazoleThe serum concentration of Bedaquiline can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PrimaquinePrimaquine may increase the QTc-prolonging activities of Bedaquiline.Approved
PrimidoneThe serum concentration of Bedaquiline can be decreased when it is combined with Primidone.Approved, Vet Approved
ProcainamideBedaquiline may increase the QTc-prolonging activities of Procainamide.Approved
PromazinePromazine may increase the QTc-prolonging activities of Bedaquiline.Approved, Vet Approved
PromethazinePromethazine may increase the QTc-prolonging activities of Bedaquiline.Approved
PropafenonePropafenone may increase the QTc-prolonging activities of Bedaquiline.Approved
PropofolPropofol may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational, Vet Approved
ProtriptylineProtriptyline may increase the QTc-prolonging activities of Bedaquiline.Approved
QuetiapineBedaquiline may increase the QTc-prolonging activities of Quetiapine.Approved
QuinidineBedaquiline may increase the QTc-prolonging activities of Quinidine.Approved
QuinineBedaquiline may increase the QTc-prolonging activities of Quinine.Approved
RanolazineRanolazine may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
RifabutinThe serum concentration of Bedaquiline can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Bedaquiline can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Bedaquiline can be decreased when it is combined with Rifapentine.Approved
RilpivirineRilpivirine may increase the QTc-prolonging activities of Bedaquiline.Approved
RisperidoneRisperidone may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
RitonavirRitonavir may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
SalbutamolSalbutamol may increase the QTc-prolonging activities of Bedaquiline.Approved, Vet Approved
SalmeterolSalmeterol may increase the QTc-prolonging activities of Bedaquiline.Approved
SaquinavirThe serum concentration of Bedaquiline can be increased when it is combined with Saquinavir.Approved, Investigational
SertralineSertraline may increase the QTc-prolonging activities of Bedaquiline.Approved
SevofluraneSevoflurane may increase the QTc-prolonging activities of Bedaquiline.Approved, Vet Approved
SildenafilThe metabolism of Bedaquiline can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Bedaquiline can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Bedaquiline can be increased when it is combined with Simeprevir.Approved
SolifenacinSolifenacin may increase the QTc-prolonging activities of Bedaquiline.Approved
SorafenibSorafenib may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
SotalolBedaquiline may increase the QTc-prolonging activities of Sotalol.Approved
St. John's WortThe serum concentration of Bedaquiline can be decreased when it is combined with St. John&#39;s Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Bedaquiline can be increased when it is combined with Stiripentol.Approved
SulfamethoxazoleSulfamethoxazole may increase the QTc-prolonging activities of Bedaquiline.Approved
SulfisoxazoleSulfisoxazole may increase the QTc-prolonging activities of Bedaquiline.Approved, Vet Approved
SunitinibSunitinib may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
TamoxifenTamoxifen may increase the QTc-prolonging activities of Bedaquiline.Approved
TelaprevirThe serum concentration of Bedaquiline can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelavancinTelavancin may increase the QTc-prolonging activities of Bedaquiline.Approved
TelithromycinThe serum concentration of Bedaquiline can be increased when it is combined with Telithromycin.Approved
TerbutalineTerbutaline may increase the QTc-prolonging activities of Bedaquiline.Approved
TetrabenazineBedaquiline may increase the QTc-prolonging activities of Tetrabenazine.Approved
ThioridazineBedaquiline may increase the QTc-prolonging activities of Thioridazine.Approved, Withdrawn
ThiothixeneThiothixene may increase the QTc-prolonging activities of Bedaquiline.Approved
TiclopidineThe metabolism of Bedaquiline can be decreased when combined with Ticlopidine.Approved
TizanidineTizanidine may increase the QTc-prolonging activities of Bedaquiline.Approved
TocilizumabThe serum concentration of Bedaquiline can be decreased when it is combined with Tocilizumab.Approved
TolterodineTolterodine may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
ToremifeneBedaquiline may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
TrazodoneTrazodone may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
TreprostinilTreprostinil may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
TrimethoprimTrimethoprim may increase the QTc-prolonging activities of Bedaquiline.Approved, Vet Approved
TrimipramineTrimipramine may increase the QTc-prolonging activities of Bedaquiline.Approved
TriptorelinTriptorelin may increase the QTc-prolonging activities of Bedaquiline.Approved, Vet Approved
VandetanibBedaquiline may increase the QTc-prolonging activities of Vandetanib.Approved
VardenafilVardenafil may increase the QTc-prolonging activities of Bedaquiline.Approved
VemurafenibBedaquiline may increase the QTc-prolonging activities of Vemurafenib.Approved
VenlafaxineVenlafaxine may increase the QTc-prolonging activities of Bedaquiline.Approved
VerapamilThe metabolism of Bedaquiline can be decreased when combined with Verapamil.Approved
VilanterolVilanterol may increase the QTc-prolonging activities of Bedaquiline.Approved
VoriconazoleThe serum concentration of Bedaquiline can be increased when it is combined with Voriconazole.Approved, Investigational
VorinostatVorinostat may increase the QTc-prolonging activities of Bedaquiline.Approved, Investigational
ZiprasidoneThe metabolism of Bedaquiline can be decreased when combined with Ziprasidone.Approved
ZuclopenthixolBedaquiline may increase the QTc-prolonging activities of Zuclopenthixol.Approved, Investigational
Food Interactions
  • When administered with food, relative bioavailability increases 2-fold

References

General References
  1. Matteelli A, Carvalho AC, Dooley KE, Kritski A: TMC207: the first compound of a new class of potent anti-tuberculosis drugs. Future Microbiol. 2010 Jun;5(6):849-58. doi: 10.2217/fmb.10.50. [PubMed:20521931]
External Links
KEGG Drug
D09872
KEGG Compound
C14122
PubChem Compound
5388906
PubChem Substance
175427143
ChemSpider
4534966
ChEBI
72292
ChEMBL
CHEMBL376488
HET
BQ1
RxList
RxList Drug Page
Wikipedia
Bedaquiline
ATC Codes
J04AK05 — Bedaquiline
PDB Entries
4v1f
FDA label
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedOtherTuberculosis1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Tuberculosis2
1CompletedTreatmentModerate Hepatic Impairment1
1CompletedTreatmentTuberculosis2
1, 2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis1
2Active Not RecruitingTreatmentTuberculosis1
2CompletedTreatmentTuberculosis3
2CompletedTreatmentTuberculosis, Pulmonary3
2Not Yet RecruitingTreatmentDrug-resistant Tuberculosis / Drug-Resistant Tuberculosis, Extremely / Tuberculosis / Tuberculosis, MDR / Tuberculosis, Multidrug Resistant / Tuberculosis, Pulmonary1
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis1
2RecruitingTreatmentPulmonary Multi-Drug Resistant Tuberculosis (MDR-TB) / Tuberculosis, Multidrug Resistant1
2RecruitingTreatmentTuberculosis, Multidrug Resistant1
2, 3RecruitingTreatmentExtensively Drug-Resistant Tuberculosis / Tuberculosis, Multidrug Resistant / Tuberculosis, Pulmonary1
2, 3RecruitingTreatmentExtensively-drug Resistant Tuberculosis / Tuberculosis / Tuberculosis, Multidrug Resistant1
3Not Yet RecruitingTreatmentExtensively Drug-Resistant Tuberculosis / Pre-XDR-TB / Tuberculosis / Tuberculosis, MDR / Tuberculosis, Multidrug Resistant / Tuberculosis, Pulmonary1
3RecruitingTreatmentMDR-TB1
3RecruitingTreatmentTuberculosis, Multidrug Resistant1
3RecruitingTreatmentTuberculosis, Pulmonary1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableApproved for MarketingNot AvailableTuberculosis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral100 mg
TabletOral100 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7498343No2004-10-022024-10-02Us
US8546428No2009-03-192029-03-19Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsoluble FDA label
Predicted Properties
PropertyValueSource
Water Solubility0.000193 mg/mLALOGPS
logP6.37ALOGPS
logP7.13ChemAxon
logS-6.5ALOGPS
pKa (Strongest Acidic)13.61ChemAxon
pKa (Strongest Basic)8.91ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area45.59 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity154.02 m3·mol-1ChemAxon
Polarizability57.29 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9811
Blood Brain Barrier+0.8854
Caco-2 permeable+0.6526
P-glycoprotein substrateSubstrate0.7553
P-glycoprotein inhibitor IInhibitor0.7137
P-glycoprotein inhibitor IIInhibitor0.5998
Renal organic cation transporterNon-inhibitor0.554
CYP450 2C9 substrateNon-substrate0.814
CYP450 2D6 substrateNon-substrate0.5081
CYP450 3A4 substrateSubstrate0.8225
CYP450 1A2 substrateInhibitor0.6983
CYP450 2C9 inhibitorNon-inhibitor0.6497
CYP450 2D6 inhibitorInhibitor0.5348
CYP450 2C19 inhibitorNon-inhibitor0.5469
CYP450 3A4 inhibitorNon-inhibitor0.6535
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5292
Ames testNon AMES toxic0.6998
CarcinogenicityNon-carcinogens0.9055
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7887 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9607
hERG inhibition (predictor II)Inhibitor0.6476
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Stilbenes
Sub Class
Not Available
Direct Parent
Stilbenes
Alternative Parents
Quinolones and derivatives / Haloquinolines / Phenylbutylamines / Naphthalenes / Alkyl aryl ethers / Aralkylamines / Aryl bromides / Pyridines and derivatives / Heteroaromatic compounds / 1,3-aminoalcohols
show 7 more
Substituents
Stilbene / Quinolone / Haloquinoline / Phenylbutylamine / Quinoline / Naphthalene / Alkyl aryl ether / Aralkylamine / Pyridine / Aryl bromide
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary alcohol, organobromine compound, tertiary amino compound, aromatic ether, quinolines, naphthalenes (CHEBI:72292)

Targets

Kind
Protein
Organism
Mycobacterium tuberculosis
Pharmacological action
Yes
Actions
Inhibitor
General Function
F(1)F(0) ATP synthase produces ATP from ADP in the presence of a proton or sodium gradient. F-type ATPases consist of two structural domains, F(1) containing the extramembraneous catalytic core and F(0) containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation.
Specific Function
Lipid binding
Gene Name
atpE
Uniprot ID
P9WPS1
Uniprot Name
ATP synthase subunit c
Molecular Weight
8055.41 Da
References
  1. Koul A, Dendouga N, Vergauwen K, Molenberghs B, Vranckx L, Willebrords R, Ristic Z, Lill H, Dorange I, Guillemont J, Bald D, Andries K: Diarylquinolines target subunit c of mycobacterial ATP synthase. Nat Chem Biol. 2007 Jun;3(6):323-4. Epub 2007 May 13. [PubMed:17496888]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da

Drug created on June 10, 2013 15:32 / Updated on November 09, 2017 04:42