Details of the Drug Combination

General Information of Drug Combination (ID: DCZ51Q1)

• Drug Combination Name: BIX-01294 + Mefloquine
• Indication: Hepatoblastoma; Status: Investigative [1]
• Component Drugs:
  BIX-01294 (DM5CBNY): Small molecular drug
  Mefloquine (DMWT905): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HB3
  Zero Interaction Potency (ZIP) Score: 3.365
  Bliss Independence Score: 2.934
  Loewe Additivity Score: 0.099
  LHighest Single Agent (HSA) Score: 2.672

Molecular Interaction Atlas of This Drug Combination

Indication(s) of BIX-01294

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Preclinical	[2]

BIX-01294 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Euchromatic histone-lysine N-methyltransferase 1 (EHMT1)	TTOFXD7	EHMT1_HUMAN	Inhibitor	[7]
Histone-lysine N-methyltransferase EHMT2 (EHMT2)	TTS6RZT	EHMT2_HUMAN	Inhibitor	[7]

BIX-01294 Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Interferon alpha-2 (IFNA2)	OT4GII73	IFNA2_HUMAN	Increases Response To Substance	[8]
Interferon regulatory factor 7 (IRF7)	OTC1A2PQ	IRF7_HUMAN	Increases Expression	[8]

Indication(s) of Mefloquine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[4]
Middle East Respiratory Syndrome (MERS)	1D64	Preclinical	[5]
Severe acute respiratory syndrome (SARS)	1D65	Preclinical	[5]
Progressive multifocal leukoencephalopathy	8A45.02	Investigative	[6]

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	[9]

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	[10]

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	[11]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
DD2	DCMEIA2	DD2	Investigative	[12]

References

• [1] 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.
• [2] Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease. Nat Rev Drug Discov. 2021 Apr;20(4):265-286.
• [3] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 019578
• [4] 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.
• [5] Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93.
• [6] Mefloquine FDA Label
• [7] Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell. 2007 Feb 9;25(3):473-81.
• [8] Inhibition of euchromatic histone methyltransferase 1 and 2 sensitizes chronic myeloid leukemia cells to interferon treatment. PLoS One. 2014 Jul 31;9(7):e103915. doi: 10.1371/journal.pone.0103915. eCollection 2014.
• [9] An ultrastructural study of the effects of mefloquine on malaria parasites. Am J Trop Med Hyg. 1987 Jan;36(1):9-14.
• [10] Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004 Jan;75(1):13-33.
• [11] Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers. J Pharm Pharmacol. 2000 Oct;52(10):1265-9.
• [12] 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.