Details of the Drug Combination

General Information of Drug Combination (ID: DCS6VIB)

• Drug Combination Name: NITD609 + Zonisamide
• Indication: Hepatoblastoma; Status: Investigative [1]
• Component Drugs:
  NITD609 (DMQHBSX): Small molecular drug
  Zonisamide (DM0DTF7): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HB3
  Zero Interaction Potency (ZIP) Score: 16.277
  Bliss Independence Score: 13.106
  Loewe Additivity Score: 2.991
  LHighest Single Agent (HSA) Score: 7.088

Molecular Interaction Atlas of This Drug Combination

Indication(s) of NITD609

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

NITD609 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Voltage-gated potassium channel Kv11.1 (KCNH2)	TTQ6VDM	KCNH2_HUMAN	Inhibitor	[5]
Adenosine A3 receptor (ADORA3)	TTJFY5U	AA3R_HUMAN	Inhibitor	[5]

Indication(s) of Zonisamide

Disease Entry	ICD 11	Status	REF
Alcohol dependence	6C40.2	Approved	[3]
Alcohol use disorder	6C40.2	Approved	[3]
Bipolar disorder	6A60	Approved	[3]
Epilepsy	8A60-8A68	Approved	[4]

Zonisamide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sodium channel unspecific (NaC)	TTRK8B9	NOUNIPROTAC	Blocker	[6]

Zonisamide Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[9]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[10]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[11]
Aldehyde oxidase (AOX)	DE8UGTM	A0A1V9IQJ2_CLOSG	Metabolism	[12]

Zonisamide Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Tyrosine 3-monooxygenase (TH)	OT6ZORKP	TY3H_HUMAN	Increases Expression	[13]

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] ClinicalTrials.gov (NCT01836458) A Study to Find the Minimum Inhibitory Concentration of KAE609 in Adult Male Patients With P. Falciparum Monoinfection. U.S. National Institutes of Health.
• [3] Zonisamide FDA Label
• [4] 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: 7047).
• [5] Spiroindolones, a potent compound class for the treatment of malaria. Science. 2010 Sep 3;329(5996):1175-80.
• [6] Antiepileptic drugs and relapse after epilepsy surgery. Epileptic Disord. 2008 Sep;10(3):193-8.
• [7] Pharmacokinetics and drug interactions with zonisamide. Epilepsia. 2007 Mar;48(3):435-41.
• [8] Actual and Predicted Pharmacokinetic Interactions Between Anticonvulsants and Antiretrovirals.
• [9] Prediction of drug-drug interactions of zonisamide metabolism in humans from in vitro data. Eur J Clin Pharmacol. 1998 Apr;54(2):177-83.
• [10] Differential catalytic properties in metabolism of endogenous and exogenous substrates among CYP3A enzymes expressed in COS-7 cells. Biochim Biophys Acta. 1998 May 8;1380(3):297-304.
• [11] Carbamazepine pharmacokinetics are not affected by zonisamide: in vitro mechanistic study and in vivo clinical study in epileptic patients. Epilepsy Res. 2004 Nov;62(1):1-11.
• [12] The role of mammalian intestinal bacteria in the reductive metabolism of zonisamide. J Pharm Pharmacol. 1997 Mar;49(3):253-6.
• [13] [The discovery of an antiparkinsonian drug, zonisamide]. Rinsho Shinkeigaku. 2010 Feb;50(2):67-73. doi: 10.5692/clinicalneurol.50.67.