Details of the Drug Combination

General Information of Drug Combination (ID: DCI96DN)

• Drug Combination Name: Captopril + Vildagliptin
• Indication: Metabolic Syndrome; Status: Phase 4 [1]
• Component Drugs:
  Captopril (DM458UM): Small molecular drug
  Vildagliptin (DMYN59P): 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	[6]
HUMAN angiotensin-converting enzyme (ACE)	TTGFNPD	ACE_HUMAN	Inhibitor	[7]

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	[8]

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	[9]
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[10]

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	[11]
Kininogen-1 (KNG1)	OT4X9LDE	KNG1_HUMAN	Increases ADR	[12]
Beta-glucuronidase (GUSB)	OT9N1DK3	BGLR_HUMAN	Increases ADR	[12]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Increases ADR	[12]
Solute carrier family 2, facilitated glucose transporter member 2 (SLC2A2)	OTBL2W7R	GTR2_HUMAN	Increases ADR	[12]
Kallikrein-10 (KLK10)	OTD573EL	KLK10_HUMAN	Increases ADR	[12]
Lysozyme C (LYZ)	OTD7H0G6	LYSC_HUMAN	Increases ADR	[12]
B2 bradykinin receptor (BDKRB2)	OTOA9D3W	BKRB2_HUMAN	Increases ADR	[12]

Indication(s) of Vildagliptin

Disease Entry	ICD 11	Status	REF
Type-2 diabetes	5A11	Approved	[5]

Vildagliptin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dipeptidyl peptidase 4 (DPP-4)	TTDIGC1	DPP4_HUMAN	Inhibitor	[13]

Vildagliptin Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[14]

Vildagliptin Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Dipeptidyl peptidase 4 (DPP4)	OT16MVL9	DPP4_HUMAN	Decreases Activity	[15]
Dipeptidyl peptidase 8 (DPP8)	OTSO9XBY	DPP8_HUMAN	Decreases Activity	[15]

References

• [1] ClinicalTrials.gov (NCT04485845) Metformin Versus Vildagliptin in Reducing Risk of Metabolic Syndrome Complications Progression
• [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] 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: 6310).
• [6] Using ACE inhibitors appropriately. Am Fam Physician. 2002 Aug 1;66(3):461-8.
• [7] Outcomes in Patients with COVID-19 Infection Taking ACEI/ARB. Curr Cardiol Rep. 2020 Apr 14;22(5):31.
• [8] Membrane transporters in drug development. Nat Rev Drug Discov. 2010 Mar;9(3):215-36.
• [9] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 Diabetes. Curr Drug Targets. 2009 Jan;10(1):71-87.
• [14] Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58.
• [15] Dipeptidyl peptidase 8/9-like activity in human leukocytes. J Leukoc Biol. 2007 May;81(5):1252-7.