Details of the Drug Combination

General Information of Drug Combination (ID: DC9NWQQ)

• Drug Combination Name: Azelnidipine + Perindopril
• Indication: Cerebral Small Vessel Diseases; Status: Phase 4 [1]
• Component Drugs:
  Azelnidipine (DMA12HL): N.A.
  Perindopril (DMOPZDT): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Azelnidipine

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[2]

Azelnidipine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[4]

Azelnidipine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2J2 (CYP2J2)	OTJBTEH8	CP2J2_HUMAN	Decreases Activity	[5]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Activity	[6]

Indication(s) of Perindopril

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[3]

Perindopril Interacts with 1 DTT Molecule(s)

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

Perindopril Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[9]
Peptide transporter 2 (SLC15A2)	DT8QKNP	S15A2_HUMAN	Substrate	[9]

Perindopril Interacts with 12 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Angiotensin-converting enzyme (ACE)	OTDF1964	ACE_HUMAN	Affects Response To Substance	[10]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[11]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Decreases Expression	[11]
Kininogen-1 (KNG1)	OT4X9LDE	KNG1_HUMAN	Decreases Expression	[12]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[13]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[13]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Expression	[13]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[13]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Expression	[13]
Secreted frizzled-related protein 4 (SFRP4)	OT8PQUVB	SFRP4_HUMAN	Affects Binding	[14]
Type-1 angiotensin II receptor (AGTR1)	OT2NRMJP	AGTR1_HUMAN	Affects Response To Substance	[15]
B2 bradykinin receptor (BDKRB2)	OTOA9D3W	BKRB2_HUMAN	Increases ADR	[16]

References

• [1] ClinicalTrials.gov (NCT01819441) Stratification of Blood Pressure Control Against Progress of Cerebral Small Vessel Diseases in Poststroke Patients
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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: 6367).
• [4] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (DRUG:D01145)
• [5] Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine. Chem Biol Interact. 2019 Jun 1;306:1-9.
• [6] Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
• [7] Angiotensin-converting enzyme activity is involved in the mechanism of increased endogenous nitric oxide synthase inhibitor in patients with type 2 diabetes mellitus. Circ J. 2002 Sep;66(9):811-5. doi: 10.1253/circj.66.811.
• [8] Fixed combination perindopril-amlodipine (Coveram) in the treatment of hypertension and coronary heart disease. Rev Med Liege. 2009 Apr;64(4):223-7.
• [9] Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41.
• [10] ACE DD genotype is more susceptible than ACE II and ID genotypes to the antiproteinuric effect of ACE inhibitors in patients with proteinuric non-insulin-dependent diabetes mellitus. Nephrol Dial Transplant. 2000 Oct;15(10):1617-23. doi: 10.1093/ndt/15.10.1617.
• [11] Experience with perindopril in normal volunteers. Arch Mal Coeur Vaiss. 1989 May;82 Spec No 1:35-41.
• [12] Long-term treatment with perindopril ameliorates dobutamine-induced myocardial ischemia in patients with coronary artery disease. Jpn J Pharmacol. 2002 Jan;88(1):100-7. doi: 10.1254/jjp.88.100.
• [13] The effects of 1 month antihypertensive treatment with perindopril, bisoprolol or both on the ex vivo ability of monocytes to secrete inflammatory cytokines. Int J Clin Pharmacol Ther. 2009 Nov;47(11):686-94. doi: 10.5414/cpp47686.
• [14] Computer aided screening of secreted frizzled-related protein 4 (SFRP4): a potential control for diabetes mellitus. Molecules. 2014 Jul 11;19(7):10129-36. doi: 10.3390/molecules190710129.
• [15] Influence of the angiotensin II type 1 receptor gene polymorphism on the effects of perindopril and nitrendipine on arterial stiffness in hypertensive individuals. Hypertension. 1996 Dec;28(6):1081-4. doi: 10.1161/01.hyp.28.6.1081.
• [16] 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.