Details of the Drug Combination

General Information of Drug Combination (ID: DC5ZOTR)

• Drug Combination Name: Biperiden + Lumefantrine
• Indication: Hepatoblastoma; Status: Investigative [1]
• Component Drugs:
  Biperiden (DME78OA): Small molecular drug
  Lumefantrine (DM29GAD): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HB3
  Zero Interaction Potency (ZIP) Score: 3.683
  Bliss Independence Score: 3.527
  Loewe Additivity Score: 0.925
  LHighest Single Agent (HSA) Score: 4.985

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Biperiden

Disease Entry	ICD 11	Status	REF
Parkinson disease	8A00.0	Approved	[2]
Parkinsonian disorder	N.A.	Approved	[3]
Postencephalitic Parkinson disease	N.A.	Approved	[3]

Biperiden Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Muscarinic acetylcholine receptor M1 (CHRM1)	TTZ9SOR	ACM1_HUMAN	Antagonist	[4]

Biperiden Interacts with 10 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[5]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Increases Expression	[5]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Expression	[5]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[5]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[5]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[6]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Increases Expression	[5]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[5]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[5]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[5]

Indication(s) of Lumefantrine

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[2]

Lumefantrine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sodium pump subunit alpha-1 (ATP1A1)	TTWK8D0	AT1A1_HUMAN	Binder	[7]

Lumefantrine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
DD2	DC6RIBT	DD2	Investigative	[9]

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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Biperiden FDA Label
• [4] Evaluation of in vivo binding properties of 3H-NMPB and 3H-QNB in mouse brain. J Neural Transm. 1999;106(7-8):583-92.
• [5] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [6] Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
• [7] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [8] Development of a paediatric physiologically based pharmacokinetic model to assess the impact of drug-drug interactions in tuberculosis co-infected malaria subjects: A case study with artemether-lumefantrine and the CYP3A4-inducer rifampicin. Eur J Pharm Sci. 2017 Aug 30;106:20-33.
• [9] 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.