Details of the Drug Combination

General Information of Drug Combination (ID: DC6XEKJ)

• Drug Combination Name: Daporinad + Mefloquine
• Indication: Diffuse intrinsic pontine glioma; Status: Investigative [1]
• Component Drugs:
  Daporinad (DMCU74R): Small molecular drug
  Mefloquine (DMWT905): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SU-DIPG-XIII
  Zero Interaction Potency (ZIP) Score: 4.625
  Bliss Independence Score: 3.097
  Loewe Additivity Score: 3.678
  LHighest Single Agent (HSA) Score: 5.569

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Daporinad

Disease Entry	ICD 11	Status	REF
leukaemia	2A60-2B33	Phase 2	[2]

Daporinad Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Nicotinamide phosphoribosyltransferase (NAMPT)	TTD1WIG	NAMPT_HUMAN	Inhibitor	[7]

Daporinad Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Axin-1 (AXIN1)	OTRGZGZ5	AXIN1_HUMAN	Increases Expression	[8]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[8]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Decreases Expression	[8]
Nicotinate phosphoribosyltransferase (NAPRT)	OTVVN0SL	PNCB_HUMAN	Decreases Activity	[9]

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	[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]

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] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7745).
• [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] Anticancer agent CHS-828 inhibits cellular synthesis of NAD. Biochem Biophys Res Commun. 2008 Mar 21;367(4):799-804.
• [8] Targeting the NAD(+) salvage pathway suppresses APC mutation-driven colorectal cancer growth and Wnt/-catenin signaling via increasing Axin level. Cell Commun Signal. 2020 Jan 31;18(1):16. doi: 10.1186/s12964-020-0513-5.
• [9] FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis. Cancer Res. 2003 Nov 1;63(21):7436-42.
• [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.