Details of the Drug Combination

General Information of Drug Combination (ID: DCIEIO3)

• Drug Combination Name: Trimethoprim + OZ277
• Indication: Hepatoblastoma; Status: Investigative [1]
• Component Drugs:
  Trimethoprim (DMM7CHK): Small molecular drug
  OZ277 (DM1YB0R): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HB3
  Zero Interaction Potency (ZIP) Score: 5.455
  Bliss Independence Score: 7.179
  Loewe Additivity Score: 0.433
  LHighest Single Agent (HSA) Score: 3.121

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Trimethoprim

Disease Entry	ICD 11	Status	REF
Acute otitis media	AB00	Approved	[2]
Bacillary dysentery	1A02	Approved	[2]
Blepharoconjunctivitis	N.A.	Approved	[2]
Pneumocystis pneumonia	CA40.20	Approved	[2]
Tuberculosis	1B10-1B14	Approved	[2]
Urinary tract infection	GC08	Approved	[3]

Trimethoprim Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dihydrofolate reductase (DHFR)	TTYZVDJ	DYR_HUMAN	Modulator	[5]

Trimethoprim Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[7]

Trimethoprim Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[9]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[10]

Trimethoprim Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Decreases Activity	[11]
HLA class II histocompatibility antigen gamma chain (CD74)	OTO16X4Q	HG2A_HUMAN	Affects Expression	[12]
HLA class II histocompatibility antigen, DO beta chain (HLA-DOB)	OTKADDUB	DOB_HUMAN	Affects Expression	[12]
Solute carrier family 22 member 3 (SLC22A3)	OTQYGVXX	S22A3_HUMAN	Increases Transport	[13]

Indication(s) of OZ277

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[4]

OZ277 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A)	TTZVSJ2	NOUNIPROTAC	Inhibitor	[4]

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] Trimethoprim FDA Label
• [3] Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.
• [4] The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Improving the prediction of the brain disposition for orally administered drugs using BDDCS. Adv Drug Deliv Rev. 2012 Jan;64(1):95-109.
• [7] Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
• [8] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [9] Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors. Basic Clin Pharmacol Toxicol. 2006 Jul;99(1):44-51.
• [10] Trimethoprim and sulfamethoxazole are selective inhibitors of CYP2C8 and CYP2C9, respectively. Drug Metab Dispos. 2002 Jun;30(6):631-5.
• [11] Cytochrome P450 inhibition potential of new psychoactive substances of the tryptamine class. Toxicol Lett. 2016 Jan 22;241:82-94.
• [12] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [13] Caki-1 cells as a model system for the interaction of renally secreted drugs with OCT3. Nephron Physiol. 2008;108(2):p18-28. doi: 10.1159/000115040. Epub 2008 Feb 4.