Details of the Drug Combination

General Information of Drug Combination (ID: DCDKVH4)

• Drug Combination Name: Acalabrutinib + Rabeprazole
• Indication: Infectious Disease; Status: Phase 1 [1]
• Component Drugs:
  Acalabrutinib (DM7GCVW): N.A.
  Rabeprazole (DMMZXIW): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Acalabrutinib

Disease Entry	ICD 11	Status	REF
leukaemia	2A60-2B33	Approved	[2]
Mantle cell lymphoma	2A85.5	Approved	[3]
Chronic lymphocytic leukaemia	2A82.0	Phase 3	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[5]

Acalabrutinib Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tyrosine-protein kinase BTK (ATK)	TTGM6VW	BTK_HUMAN	Inhibitor	[3]
HUMAN bruton tyrosine kinase (BTK)	TTOWPER	BTK_HUMAN	Inhibitor	[8]

Acalabrutinib Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[9]

Acalabrutinib Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Affects Expression	[10]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Expression	[10]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Metabolism	[11]

Indication(s) of Rabeprazole

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[6]
Gastrinoma	2C10.1	Approved	[7]
Peptic ulcer	DA61	Approved	[7]

Rabeprazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Gastric H(+)/K(+) ATPase alpha (ATP4A)	TTF1QVM	ATP4A_HUMAN	Inhibitor	[12]

Rabeprazole Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[13]

Rabeprazole Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[14]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[14]

References

• [1] ClinicalTrials.gov (NCT04489797) A Study to Evaluate Effects of Proton-pump Inhibitor on Acalabrutinib Capsule When Administered Orally With COCA-COLA in Healthy Participants
• [2] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 210259
• [3] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] ClinicalTrials.gov (NCT04346199) Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19.. U.S. National Institutes of Health.
• [6] 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: 7290).
• [7] Rabeprazole FDA Label
• [8] AstraZeneca initiates CALAVI clinical trial with Calquence against COVID-19
• [9] FDA label of Acalabrutinib. The 2020 official website of the U.S. Food and Drug Administration.
• [10] Inhibition of Bruton tyrosine kinase in patients with severe COVID-19. Sci Immunol. 2020 Jun 5;5(48):eabd0110. doi: 10.1126/sciimmunol.abd0110. Epub 2020 Jun 5.
• [11] Functional assessment of the effects of CYP3A4 variants on acalabrutinib metabolism in vitro. Chem Biol Interact. 2021 Aug 25;345:109559. doi: 10.1016/j.cbi.2021.109559. Epub 2021 Jun 18.
• [12] Review article: rabeprazole's tolerability profile in clinical trials. Aliment Pharmacol Ther. 1999 Oct;13 Suppl 5:17-23.
• [13] Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy. Br J Clin Pharmacol. 2009 Jan;67(1):44-9.
• [14] Effects of clarithromycin and verapamil on rabeprazole pharmacokinetics between CYP2C19 genotypes. Eur J Clin Pharmacol. 2006 Aug;62(8):597-603.