Details of the Drug Combination

General Information of Drug Combination (ID: DC255BE)

• Drug Combination Name: Captopril + Erlotinib
• Indication: Carcinoma, Large Cell; Status: Phase 1 [1]
• Component Drugs:
  Captopril (DM458UM): Small molecular drug
  Erlotinib (DMCMBHA): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Captopril

Disease Entry	ICD 11	Status	REF
Chronic heart failure	BD1Z	Approved	[2]
Diabetic kidney disease	GB61.Z	Approved	[2]
Hypertension	BA00-BA04	Approved	[3]
Malignant essential hypertension	BA00	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[4]

Captopril Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Angiotensin-converting enzyme (ACE)	TTL69WB	ACE_HUMAN	Inhibitor	[7]
HUMAN angiotensin-converting enzyme (ACE)	TTGFNPD	ACE_HUMAN	Inhibitor	[8]

Captopril Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[9]

Captopril Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[10]
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[11]

Captopril Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Decreases Response To Substance	[12]
Kininogen-1 (KNG1)	OT4X9LDE	KNG1_HUMAN	Increases ADR	[13]
Beta-glucuronidase (GUSB)	OT9N1DK3	BGLR_HUMAN	Increases ADR	[13]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Increases ADR	[13]
Solute carrier family 2, facilitated glucose transporter member 2 (SLC2A2)	OTBL2W7R	GTR2_HUMAN	Increases ADR	[13]
Kallikrein-10 (KLK10)	OTD573EL	KLK10_HUMAN	Increases ADR	[13]
Lysozyme C (LYZ)	OTD7H0G6	LYSC_HUMAN	Increases ADR	[13]
B2 bradykinin receptor (BDKRB2)	OTOA9D3W	BKRB2_HUMAN	Increases ADR	[13]

Indication(s) of Erlotinib

Disease Entry	ICD 11	Status	REF
Adrenal gland neoplasm	N.A.	Approved	[5]
Adult hepatocellular carcinoma	N.A.	Approved	[5]
Brain cancer	2A00	Approved	[5]
Esophageal disorder	N.A.	Approved	[5]
Lung cancer	2C25.0	Approved	[5]
Non-small-cell lung cancer	2C25.Y	Approved	[6]
Pancreatic adenocarcinoma	N.A.	Approved	[5]
Psoriasis	EA90	Approved	[5]
Salivary gland squamous cell carcinoma	N.A.	Approved	[5]
Pancreatic cancer	2C10	Phase 3	[6]
Colon cancer	2B90.Z	Phase 2	[6]
Ependymoma	2A00.0Y	Investigative	[5]
Neoplastic meningitis	N.A.	Investigative	[5]
Neuroblastoma	2D11.2	Investigative	[5]

Erlotinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[14]

Erlotinib Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[15]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[16]

Erlotinib Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[17]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[18]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[18]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[18]

Erlotinib Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Increases Response	[19]

References

• [1] ClinicalTrials.gov (NCT00673049) Trial Of CP-751, 871 And Erlotinib In Refractory Lung Cancer
• [2] Captopril FDA Label
• [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: 5158).
• [4] ClinicalTrials.gov (NCT04345406) Angiotensin Converting Enzyme Inhibitors in Treatment of Covid 19. U.S. National Institutes of Health.
• [5] Erlotinib FDA Label
• [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: 4920).
• [7] Using ACE inhibitors appropriately. Am Fam Physician. 2002 Aug 1;66(3):461-8.
• [8] Outcomes in Patients with COVID-19 Infection Taking ACEI/ARB. Curr Cardiol Rep. 2020 Apr 14;22(5):31.
• [9] Membrane transporters in drug development. Nat Rev Drug Discov. 2010 Mar;9(3):215-36.
• [10] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [11] S-methylation of captopril. Demonstration of captopril thiol methyltransferase activity in human erythrocytes and enzyme distribution in rat tissues. Biochem Pharmacol. 1983 May 15;32(10):1557-62.
• [12] Polymorphisms of ACE2 gene are associated with essential hypertension and antihypertensive effects of Captopril in women. Clin Pharmacol Ther. 2007 Aug;82(2):187-96. doi: 10.1038/sj.clpt.6100214. Epub 2007 May 2.
• [13] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [14] Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
• [15] Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol Cancer Ther. 2008 Aug;7(8):2280-7.
• [16] Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. Adv Drug Deliv Rev. 2009 Jan 31;61(1):26-33.
• [17] In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9.
• [18] Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706.
• [19] Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004 May 20;350(21):2129-39. doi: 10.1056/NEJMoa040938. Epub 2004 Apr 29.