Details of the Drug Combination

General Information of Drug Combination (ID: DCL38ZQ)

• Drug Combination Name: NITD609 + Nisoldipine
• Indication: Hepatoblastoma; Status: Investigative [1]
• Component Drugs:
  NITD609 (DMQHBSX): Small molecular drug
  Nisoldipine (DM7ISKJ): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HB3
  Zero Interaction Potency (ZIP) Score: 13.44
  Bliss Independence Score: 7.02
  Loewe Additivity Score: 4.34
  LHighest Single Agent (HSA) Score: 3.92

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	[4]
Adenosine A3 receptor (ADORA3)	TTJFY5U	AA3R_HUMAN	Inhibitor	[4]

Indication(s) of Nisoldipine

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[3]

Nisoldipine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Calcium channel unspecific (CaC)	TT5HONZ	NOUNIPROTAC	Blocker	[5]

Nisoldipine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]

Nisoldipine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[8]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[8]

Nisoldipine Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[9]
Cytochrome P450 2J2 (CYP2J2)	OTJBTEH8	CP2J2_HUMAN	Decreases Activity	[10]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Activity	[11]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Decreases Expression	[12]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Activity	[11]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Activity	[11]

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] 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: 2524).
• [4] Spiroindolones, a potent compound class for the treatment of malaria. Science. 2010 Sep 3;329(5996):1175-80.
• [5] RT-PCR and pharmacological analysis of L-and T-type calcium channels in rat carotid body. Adv Exp Med Biol. 2009;648:105-12.
• [6] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [7] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [8] Drug Interactions Flockhart Table
• [9] Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52.
• [10] Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine. Chem Biol Interact. 2019 Jun 1;306:1-9.
• [11] Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
• [12] Plasma endothelin-1 concentrations in patients with coronary artery disease during stress test before and after nisoldipine administration. Acta Cardiol. 1996;51(2):165-72.