Details of the Drug Combination

General Information of Drug Combination (ID: DCX979N)

• Drug Combination Name: Linezolid + Bedaquiline
• Indication: Tuberculosis, Multidrug-Resistant; Status: Phase 2 [1]
• Component Drugs:
  Linezolid (DMGFPU2): Small molecular drug
  Bedaquiline (DM3906J): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Linezolid

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[2]
Bacterial infection	1A00-1C4Z	Approved	[3]
Staphylococcal pneumonia	N.A.	Approved	[2]
Staphylococcus aureus infection	N.A.	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[4]
Skin infection	1F28-1G0Z	Investigative	[2]

Linezolid Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial 23S ribosomal RNA (Bact 23S rRNA)	TTLFGBV	NOUNIPROTAC	Binder	[7]

Linezolid Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Amine oxidase A (MAOA)	OT8NIWMQ	AOFA_HUMAN	Decreases Activity	[8]
Amine oxidase B (MAOB)	OTTDFM1O	AOFB_HUMAN	Decreases Activity	[8]

Indication(s) of Bedaquiline

Disease Entry	ICD 11	Status	REF
Drug-resistant tuberculosis	N.A.	Approved	[5]
Multi-drug resistant tuberculosis	MG52.00	Approved	[6]
Pulmonary tuberculosis	1B10.Z	Approved	[5]

Bedaquiline Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Mycobacterium Proton pump (MycB Prop)	TT19K0L	A0A1Q4HQH4_9MYCO	Modulator	[9]

Bedaquiline Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Tuberculosis, Multidrug-Resistant	DCCPSGD	N. A.	Phase 3	[11]
Pulmonary Tuberculosis	DCSYM2Q	N. A.	Phase 3	[12]
Multi-drug Resistant Tuberculosis	DCDV0TP	N. A.	Phase 2	[13]
Multi-drug Resistant Tuberculosis	DCLF1FC	N. A.	Phase 2	[13]
Tuberculosis, Multidrug-Resistant	DCYP39B	N. A.	Phase 2	[1]
Tuberculosis, Multidrug-Resistant	DC7VMU1	N. A.	Phase 2	[1]
Multi-drug Resistant Tuberculosis	DCMV1JA	N. A.	Phase 2	[13]

References

• [1] ClinicalTrials.gov (NCT02589782) Pragmatic Clinical Trial for a More Effective Concise and Less Toxic MDR-TB Treatment Regimen(s)
• [2] Linezolid FDA Label
• [3] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 200222.
• [4] Therapeutic and Triage Strategies for 2019 Novel Coronavirus Disease in Fever Clinics. Lancet Respir Med. 2020 Mar;8(3):e11-e12.
• [5] Bedaquiline FDA Label
• [6] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [7] Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance. Genome Res. 2009 Jul;19(7):1214-23.
• [8] Nonclinical Evaluation of Antibacterial Oxazolidinones Contezolid and Contezolid Acefosamil with Low Serotonergic Neurotoxicity. Chem Res Toxicol. 2021 May 17;34(5):1348-1354. doi: 10.1021/acs.chemrestox.0c00524. Epub 2021 Apr 29.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [10] Bedaquiline metabolism: enzymes and novel metabolites. Drug Metab Dispos. 2014 May;42(5):863-6.
• [11] ClinicalTrials.gov (NCT02754765) Evaluating Newly Approved Drugs for Multidrug-resistant TB
• [12] ClinicalTrials.gov (NCT02333799) A Phase 3 Study Assessing the Safety and Efficacy of Bedaquiline Plus PA-824 Plus Linezolid in Subjects With Drug Resistant Pulmonary Tuberculosis
• [13] ClinicalTrials.gov (NCT04207112) Economic Evaluation of New MDR TB Regimens