Details of the Drug Combination

General Information of Drug Combination (ID: DCEO4FI)

• Drug Combination Name: F901318 + Pantoprazole
• Indication: Invasive Aspergillosis; Status: Phase 1 [1]
• Component Drugs:
  F901318 (DM2CUS0): Small molecular drug
  Pantoprazole (DMSVOCZ): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of F901318

Disease Entry	ICD 11	Status	REF
Fungal infection	1F29-1F2F	Phase 2	[2]

F901318 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aspergillus Dihydroorotate dehydrogenase (Aspergillus DHODH)	TTTSUI2	G5EB61_EMENI	Inhibitor	[5]

Indication(s) of Pantoprazole

Disease Entry	ICD 11	Status	REF
Gastrinoma	2C10.1	Approved	[3]
Gastroesophageal reflux disease	DA22.Z	Approved	[4]
Peptic ulcer	DA61	Approved	[3]

Pantoprazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Gastric H(+)/K(+) ATPase (Proton pump)	TTLOKXP	ATP4A_HUMAN; ATP4B_HUMAN	Modulator	[6]

Pantoprazole Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[8]

Pantoprazole Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[10]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[9]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[11]

Pantoprazole Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Phospholipid-transporting ATPase ABCA1 (ABCA1)	OT94G6BQ	ABCA1_HUMAN	Increases Expression	[12]
Hepcidin (HAMP)	OT607RBL	HEPC_HUMAN	Increases Expression	[13]

References

• [1] ClinicalTrials.gov (NCT03095547) Drug/Drug Interactions With F901318
• [2] ClinicalTrials.gov (NCT03583164) Evaluate F901318 Treatment of Invasive Fungal Infections in Patients Lacking Treatment Options (FORMULA-OLS). U.S. National Institutes of Health.
• [3] Pantoprazole 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: 7260).
• [5] Effect of the Novel Antifungal Drug F901318 (Olorofim) on Growth and Viability of Aspergillus fumigatus. Antimicrob Agents Chemother. 2018 Jul 27;62(8):e00231-18.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] A novel screening strategy to identify ABCB1 substrates and inhibitors. Naunyn Schmiedebergs Arch Pharmacol. 2009 Jan;379(1):11-26.
• [8] Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles: potential role for breast cancer resistance protein in clinical drug-drug interactions. Cancer Res. 2004 Aug 15;64(16):5804-11.
• [9] Interaction of proton pump inhibitors with cytochromes P450: consequences for drug interactions. Yale J Biol Med. 1996 May-Jun;69(3):203-9.
• [10] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [11] Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine. Expert Opin Drug Metab Toxicol. 2018 Apr;14(4):447-460.
• [12] Proton pump inhibitor lansoprazole is a nuclear liver X receptor agonist. Biochem Pharmacol. 2010 May 1;79(9):1310-6. doi: 10.1016/j.bcp.2009.12.018. Epub 2010 Jan 8.
• [13] Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway. Toxicol Lett. 2020 Jan;318:86-91. doi: 10.1016/j.toxlet.2019.10.016. Epub 2019 Oct 24.