bedaquiline 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
4741 843663-66-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • bedaquiline
  • sirturo
  • TMC207
  • bedaquiline fumarate
Bedaquiline is a diarylquinoline antimycobacterial drug that inhibits mycobacterial ATP (adenosine 5'-triphosphate) synthase, by binding to subunit c of the enzyme that is essential for the generation of energy in M. tuberculosis.
  • Molecular weight: 555.52
  • Formula: C32H31BrN2O2
  • CLOGP: 7.25
  • LIPINSKI: 2
  • HAC: 4
  • HDO: 1
  • TPSA: 45.59
  • ALOGS: -6.46
  • ROTB: 8
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
86 mg O

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.581 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.690 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 0.089 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 7.998 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.140 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 0.270 % High 1
herg hERG pIC50 5.103 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 2.415 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 14.997 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.360 % High 1
kinase-safety-class ACVR2B,AKT1,AKT2,AKT3,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,ITK,JAK2,JAK3,MAP3K21,MAP3K7,MAPK10,MAPK12,MAPK7,MAPK9,MAPKAPK2,MET,MTOR,NTRK2,PDK2,PDK4,PDPK1,PIK3CB,PIM2,PRKDC,SIK2,SIK3,STK33,TEK,TTK 43
kinase-selectivity-class AXL,EIF2AK3,ERBB2,PDK4 4
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.512 High 1
mh-clint Mouse hepatocyte intrinsic clearance 17.865 High 1
mppb Mouse plasma protein binding (% unbound) 0.220 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 0.480 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 0.390 % High 1
rh-clint Rat hepatocyte intrinsic clearance 10.715 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 0.140 % High 1
rppb Rat plasma protein binding (% unbound) 0.280 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 2.399 uM High 1

Approvals:

DateAgencyCompanyOrphan
Jan. 19, 2018 PMDA Janssen Pharmaceutical KK
Dec. 28, 2012 FDA JANSSEN THERAP

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Electrocardiogram QT prolonged 548.77 31.43 183 4184 72273 90551807
Neuropathy peripheral 268.84 31.43 131 4236 136839 90487241
Anaemia 189.07 31.43 147 4220 352655 90271425
Hepatotoxicity 154.10 31.43 64 4303 45778 90578302
Off label use 108.79 31.43 191 4176 1102061 89522019
Intentional product use issue 62.76 31.43 64 4303 216828 90407252
Drug resistance 56.12 31.43 28 4339 30421 90593659
Optic neuritis 55.68 31.43 20 4347 9658 90614422
Polyneuropathy 54.96 31.43 24 4343 19317 90604763
Vomiting 54.48 31.43 118 4249 788175 89835905
Drug-induced liver injury 51.01 31.43 39 4328 90279 90533801
Aspartate aminotransferase increased 50.71 31.43 41 4326 102896 90521184
Immune reconstitution inflammatory syndrome associated tuberculosis 50.26 31.43 10 4357 493 90623587
Alanine aminotransferase increased 49.74 31.43 43 4324 118295 90505785
Death 48.30 31.43 82 4285 456469 90167611
Respiratory failure 47.70 31.43 42 4325 118376 90505704
Meningitis tuberculous 47.58 31.43 10 4357 648 90623432
Cardiopulmonary failure 41.37 31.43 13 4354 4175 90619905
Psychotic disorder 41.27 31.43 23 4344 31207 90592873
Hypokalaemia 40.27 31.43 40 4327 131076 90493004
Butterfly rash 40.26 31.43 11 4356 2174 90621906
Haemoptysis 39.89 31.43 23 4344 33297 90590783
Deafness 39.41 31.43 20 4347 22494 90601586
Pyelonephritis chronic 37.89 31.43 7 4360 232 90623848
Hypomagnesaemia 35.90 31.43 22 4345 35566 90588514
Herbal toxicity 34.84 31.43 5 4362 31 90624049
Disturbance in social behaviour 33.20 31.43 11 4356 4177 90619903
Myelosuppression 32.14 31.43 24 4343 53567 90570513
Gastroenteritis 31.88 31.43 19 4348 29210 90594870

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Electrocardiogram QT prolonged 817.31 29.62 277 4692 47668 42568698
Hepatotoxicity 449.24 29.62 151 4818 25016 42591350
Neuropathy peripheral 296.86 29.62 170 4799 101683 42514683
Anaemia 188.71 29.62 195 4774 280083 42336283
Intentional product use issue 164.76 29.62 103 4866 71730 42544636
Off label use 152.36 29.62 267 4702 638068 41978298
Optic neuritis 115.52 29.62 35 4934 4107 42612259
Drug-induced liver injury 80.38 29.62 52 4917 38221 42578145
Tuberculosis 71.66 29.62 31 4938 10068 42606298
Drug resistance 68.16 29.62 45 4924 34203 42582163
Death 52.50 29.62 146 4823 471039 42145327
Aspartate aminotransferase increased 51.98 29.62 54 4915 77109 42539257
Polyneuropathy 50.97 29.62 30 4939 18631 42597735
Vomiting 50.70 29.62 107 4862 289616 42326750
Toxic optic neuropathy 47.91 29.62 13 4956 1027 42615339
Cardiopulmonary failure 42.03 29.62 17 4952 4666 42611700
Incorrect product administration duration 41.54 29.62 18 4951 5862 42610504
Treatment noncompliance 36.02 29.62 32 4937 37640 42578726
Alcohol poisoning 34.19 29.62 17 4952 7557 42608809
Myelosuppression 34.06 29.62 32 4937 40429 42575937
Hypoacusis 33.41 29.62 23 4946 18679 42597687
Pulmonary tuberculosis 32.95 29.62 15 4954 5486 42610880
Deafness neurosensory 31.57 29.62 13 4956 3733 42612633
Hypokalaemia 31.07 29.62 40 4929 71681 42544685
HIV infection 30.75 29.62 10 4959 1475 42614891
Psychotic disorder 30.31 29.62 26 4943 29182 42587184
Alanine aminotransferase increased 30.28 29.62 44 4925 88362 42528004
Electrocardiogram T wave inversion 29.98 29.62 11 4958 2323 42614043

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Electrocardiogram QT prolonged 1327.91 30.07 448 8574 108512 110471765
Hepatotoxicity 579.04 30.07 211 8811 63189 110517088
Neuropathy peripheral 577.10 30.07 284 8738 178993 110401284
Anaemia 377.40 30.07 329 8693 546757 110033520
Off label use 248.52 30.07 438 8584 1499747 109080530
Intentional product use issue 198.52 30.07 163 8859 247743 110332534
Optic neuritis 167.60 30.07 54 8968 11093 110569184
Drug-induced liver injury 110.95 30.07 86 8936 119981 110460296
Polyneuropathy 109.30 30.07 53 8969 31959 110548318
Death 109.16 30.07 200 8822 698669 109881608
Aspartate aminotransferase increased 105.03 30.07 94 8928 159842 110420435
Drug resistance 104.06 30.07 62 8960 56312 110523965
Vomiting 89.95 30.07 216 8806 910459 109669818
Alanine aminotransferase increased 79.50 30.07 86 8936 183687 110396590
Psychotic disorder 78.65 30.07 50 8972 50887 110529390
Tuberculosis 74.77 30.07 34 8988 17740 110562537
Meningitis tuberculous 64.65 30.07 16 9006 1262 110579015
Cardiopulmonary failure 63.48 30.07 24 8998 7879 110572398
Myelosuppression 62.96 30.07 56 8966 94284 110485993
Deafness 61.65 30.07 34 8988 26675 110553602
Incorrect product administration duration 61.23 30.07 31 8991 20467 110559810
Hypokalaemia 59.76 30.07 74 8948 182374 110397903
Respiratory failure 59.06 30.07 80 8942 215252 110365025
Optic neuropathy 55.73 30.07 19 9003 4639 110575638
Hepatitis toxic 51.27 30.07 19 9003 5902 110574375
Hypoacusis 50.50 30.07 33 8989 35158 110545119
Pulmonary tuberculosis 49.87 30.07 21 9001 9118 110571159
Toxic optic neuropathy 49.35 30.07 13 9009 1315 110578962
Haemoptysis 48.89 30.07 43 8979 71311 110508966
Product use in unapproved indication 45.95 30.07 108 8914 447269 110133008
Treatment noncompliance 44.13 30.07 41 8981 72949 110507328
Pain 43.70 30.07 12 9010 954943 109625334
Tinnitus 40.50 30.07 36 8986 60504 110519773
Nausea 39.78 30.07 202 8820 1235488 109344789
Fatigue 37.36 30.07 27 8995 1215931 109364346
Pneumothorax 36.35 30.07 27 8995 35258 110545019
Haemoglobin decreased 35.87 30.07 69 8953 248658 110331619
Butterfly rash 34.80 30.07 11 9011 2120 110578157
Electrocardiogram T wave inversion 34.19 30.07 14 9008 5666 110574611
Hypomagnesaemia 32.85 30.07 32 8990 60338 110519939
Pyelonephritis chronic 32.69 30.07 7 9015 290 110579987
Gastroenteritis 31.95 30.07 26 8996 38774 110541503
Ototoxicity 31.22 30.07 12 9010 4119 110576158
Alcohol poisoning 30.97 30.07 15 9007 9005 110571272
Blood sodium decreased 30.13 30.07 25 8997 38294 110541983

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J04AK05 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIMYCOBACTERIALS
DRUGS FOR TREATMENT OF TUBERCULOSIS
Other drugs for treatment of tuberculosis
FDA CS M0582947 Diarylquinolines
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000900 Anti-Bacterial Agents
MeSH PA D000995 Antitubercular Agents
FDA EPC N0000186775 Diarylquinoline Antimycobacterial
CHEBI has role CHEBI:20854 ATP synthase inhibitor
CHEBI has role CHEBI:33231 antitubercular agent
CHEBI has role CHEBI:33282 antibacterial agent
CHEBI has role CHEBI:35816 leprostatic drug

Related Drugs by ATC class:

J04AK Other drugs for treatment of tuberculosis 7 drugs
delamanidethambutolmorinamidepretomanidpyrazinamideterizidonethioacetazone

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Pulmonary tuberculosis indication 154283005 DOID:2957
Drug resistant tuberculosis indication 423709000




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.93 acidic
pKa2 8.89 Basic
pKa3 2.19 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 100MG BASE SIRTURO JANSSEN THERAP N204384 Dec. 28, 2012 RX TABLET ORAL 7498343 Dec. 1, 2026 TREATMENT OF PULMONARY MULTI-DRUG RESISTANT TUBERCULOSIS
EQ 20MG BASE SIRTURO JANSSEN THERAP N204384 May 27, 2020 RX TABLET ORAL 7498343 Dec. 1, 2026 TREATMENT OF PULMONARY MULTI-DRUG RESISTANT TUBERCULOSIS
EQ 100MG BASE SIRTURO JANSSEN THERAP N204384 Dec. 28, 2012 RX TABLET ORAL 8546428 March 19, 2029 TREATMENT OF PULMONARY MULTI-DRUG RESISTANT TUBERCULOSIS
EQ 20MG BASE SIRTURO JANSSEN THERAP N204384 May 27, 2020 RX TABLET ORAL 8546428 March 19, 2029 TREATMENT OF PULMONARY MULTI-DRUG RESISTANT TUBERCULOSIS

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 100MG BASE SIRTURO JANSSEN THERAP N204384 Dec. 28, 2012 RX TABLET ORAL Aug. 9, 2026 INDICATED AS PART OF COMBINATION THERAPY IN THE TREATMENT OF PEDIATRIC PATIENTS (12 TO LESS THAN 18 YEARS OF AGE AND WEIGHING AT LEAST 30 KG) WITH PULMONARY MULTI-DRUG RESISTANT TUBERCULOSIS
EQ 20MG BASE SIRTURO JANSSEN THERAP N204384 May 27, 2020 RX TABLET ORAL Aug. 9, 2026 FDA HAS NOT RECOGNIZED ORPHAN-DRUG EXCLUSIVITY (ODE) FOR THIS DRUG, BUT IT CONTAINS THE SAME ACTIVE MOIETY OR MOIETIES AS ANOTHER DRUG(S) THAT WAS ELIGIBLE FOR ODE, AND ALSO SHARES ODE-PROTECTED USE(S) OR INDICATION(S) WITH THAT DRUG(S). AN APPLICATION SEEKING APPROVAL FOR THE SAME ACTIVE MOIETY OR MOIETIES, INCLUDING AN ANDA THAT CITES THIS NDA AS ITS BASIS OF SUBMISSION, MAY NOT BE APPROVED FOR SUCH ODE-PROTECTED USE(S) AND INDICATION(S)
EQ 100MG BASE SIRTURO JANSSEN THERAP N204384 Dec. 28, 2012 RX TABLET ORAL May 27, 2027 INDICATED AS PART OF COMBINATION THERAPY IN THE TREATMENT OF PEDIATRIC PATIENTS 5 YEARS AND OLDER TO LESS THAN 12 YEARS OF AGE AND WEIGHING AT LEAST 15 KG WITH PULMONARY MULTI-DRUG RESISTANT TUBERCULOSIS (MDR-TB)
EQ 20MG BASE SIRTURO JANSSEN THERAP N204384 May 27, 2020 RX TABLET ORAL May 27, 2027 INDICATED AS PART OF COMBINATION THERAPY IN THE TREATMENT OF PEDIATRIC PATIENTS 5 YEARS AND OLDER TO LESS THAN 12 YEARS OF AGE AND WEIGHING AT LEAST 15 KG WITH PULMONARY MULTI-DRUG RESISTANT TUBERCULOSIS (MDR-TB)
EQ 100MG BASE SIRTURO JANSSEN THERAP N204384 Dec. 28, 2012 RX TABLET ORAL June 21, 2027 REVISIONS TO THE LABELING TO REFLECT THE RESULTS OF A CLINICAL STUDY TO FULFILL POST MARKETING REQUIREMENT 1988-001
EQ 20MG BASE SIRTURO JANSSEN THERAP N204384 May 27, 2020 RX TABLET ORAL June 21, 2027 REVISIONS TO THE LABELING TO REFLECT THE RESULTS OF A CLINICAL STUDY TO FULFILL POST MARKETING REQUIREMENT 1988-001

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 6.43 CHEMBL
ATP synthase Enzyme INHIBITOR CHEMBL CHEMBL
ATP synthase subunit c Enzyme IC50 8.60 CHEMBL
ATP synthase subunit c Enzyme Kd 6.30 CHEMBL

External reference:

IDSource
78846I289Y UNII
D09872 KEGG_DRUG
4032353 VUID
N0000187065 NUI
4032353 VANDF
C1664205 UMLSCUI
CHEBI:72292 CHEBI
BQ1 PDB_CHEM_ID
CHEMBL376488 ChEMBL_ID
5388906 PUBCHEM_CID
DB08903 DRUGBANK_ID
CHEMBL2105700 ChEMBL_ID
9316 INN_ID
C493870 MESH_SUPPLEMENTAL_RECORD_UI
11171 IUPHAR_LIGAND_ID
845533-86-0 SECONDARY_CAS_RN
1364503 RXNORM
196758 MMSL
29035 MMSL
30320 MMSL
d07941 MMSL
014821 NDDF
014822 NDDF
1010553003 SNOMEDCT_US
714086004 SNOMEDCT_US
714087008 SNOMEDCT_US
78846I289Y INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
SIRTURO HUMAN PRESCRIPTION DRUG LABEL 1 59676-701 TABLET 100 mg ORAL NDA 34 sections
SIRTURO HUMAN PRESCRIPTION DRUG LABEL 1 59676-701 TABLET 100 mg ORAL NDA 34 sections
SIRTURO HUMAN PRESCRIPTION DRUG LABEL 1 59676-702 TABLET 20 mg ORAL NDA 34 sections
SIRTURO HUMAN PRESCRIPTION DRUG LABEL 1 59676-702 TABLET 20 mg ORAL NDA 34 sections