Details of the Drug Combination

General Information of Drug Combination (ID: DC4AC75)

• Drug Combination Name: Thiolactomycin + Mefloquine
• Indication: DD2; Status: Investigative [1]
• Component Drugs:
  Thiolactomycin (DMBAWDG): Small molecular drug
  Mefloquine (DMWT905): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DD2
  Zero Interaction Potency (ZIP) Score: 0.705
  Bliss Independence Score: 4.722
  Loewe Additivity Score: 3.195
  LHighest Single Agent (HSA) Score: 6.044

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Thiolactomycin

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Investigative	[2]
Urinary tract infection	GC08	Investigative	[3]

Thiolactomycin Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial Beta-ketoacyl-ACP synthase I (Bact fabB)	TT0O4QL	FABB_ECOL6	Binder	[2]
Plasmodium Enoyl-ACP reductase (Malaria fabI)	TTNX2CS	Q965D5_PLAFA	Inhibitor	[8]
Bacterial Beta-ketoacyl-ACP synthase III (Bact fabH)	TTRVTMX	FABH_ECOLI	Binder	[9]
Bacterial Oxoacyl-[acyl-carrier-protein] synthase II (Bact fabF)	TTRFV0W	FABF_ECOLI	Binder	[2]

Indication(s) of Mefloquine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[5]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[6]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[6]
Progressive multifocal leukoencephalopathy	8A45.02	Investigative	[7]

Mefloquine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Plasmodium 80S ribosome (Malaria 80S)	TTT28H3	NOUNIPROTAC	Binder	[10]

Mefloquine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]

Mefloquine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Hepatoblastoma	DCKKKQ0	HB3	Investigative	[13]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
• [3] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [4] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 019578
• [5] ClinicalTrials.gov (NCT04347031) An Open Randomized Study of the Effectiveness of Mefloquine for the Treatment of Patients With COVID19. U.S. National Institutes of Health.
• [6] Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93.
• [7] Mefloquine FDA Label
• [8] Novel molecular targets for antimalarial drug development. Chem Biol Drug Des. 2008 Apr;71(4):287-97.
• [9] The apicoplast as an antimalarial drug target. Drug Resist Updat. 2001 Jun;4(3):145-51.
• [10] An ultrastructural study of the effects of mefloquine on malaria parasites. Am J Trop Med Hyg. 1987 Jan;36(1):9-14.
• [11] Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004 Jan;75(1):13-33.
• [12] Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers. J Pharm Pharmacol. 2000 Oct;52(10):1265-9.
• [13] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.