Details of the Drug Combination

General Information of Drug Combination (ID: DC95QEC)

• Drug Combination Name: Captopril + Irbesartan
• Indication: Type 2 Diabetes Mellitus; Status: Phase 1 [1]
• Component Drugs:
  Captopril (DM458UM): Small molecular drug
  Irbesartan (DMTP1DC): 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	[8]
HUMAN angiotensin-converting enzyme (ACE)	TTGFNPD	ACE_HUMAN	Inhibitor	[9]

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	[10]

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	[11]
Thiopurine methyltransferase (TPMT)	DEFQ8VO	TPMT_HUMAN	Metabolism	[12]

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	[13]
Kininogen-1 (KNG1)	OT4X9LDE	KNG1_HUMAN	Increases ADR	[14]
Beta-glucuronidase (GUSB)	OT9N1DK3	BGLR_HUMAN	Increases ADR	[14]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Increases ADR	[14]
Solute carrier family 2, facilitated glucose transporter member 2 (SLC2A2)	OTBL2W7R	GTR2_HUMAN	Increases ADR	[14]
Kallikrein-10 (KLK10)	OTD573EL	KLK10_HUMAN	Increases ADR	[14]
Lysozyme C (LYZ)	OTD7H0G6	LYSC_HUMAN	Increases ADR	[14]
B2 bradykinin receptor (BDKRB2)	OTOA9D3W	BKRB2_HUMAN	Increases ADR	[14]

Indication(s) of Irbesartan

Disease Entry	ICD 11	Status	REF
Diabetic kidney disease	GB61.Z	Approved	[5]
Hypertension	BA00-BA04	Approved	[6]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[7]
High blood pressure	BA00	Investigative	[5]

Irbesartan Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Angiotensin II receptor type-1 (AGTR1)	TT8DBY3	AGTR1_HUMAN	Antagonist	[15]
HUMAN type-1 angiotensin II receptor (AGTR1)	TTPKMXQ	AGTR1_HUMAN	Antagonist	[16]

Irbesartan Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[17]

Irbesartan Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[18]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[19]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[20]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[21]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Metabolism	[21]

Irbesartan Interacts with 18 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Decreases Activity	[19]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[22]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Expression	[23]
Carbonic anhydrase 1 (CA1)	OTNFBVVQ	CAH1_HUMAN	Decreases Activity	[24]
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Increases Expression	[25]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Increases Expression	[26]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[27]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Decreases Expression	[27]
Proto-oncogene tyrosine-protein kinase receptor Ret (RET)	OTLU040A	RET_HUMAN	Increases Expression	[28]
Type-1 angiotensin II receptor (AGTR1)	OT2NRMJP	AGTR1_HUMAN	Affects Response To Substance	[29]
Endoplasmic reticulum aminopeptidase 1 (ERAP1)	OT72S99B	ERAP1_HUMAN	Affects Response To Substance	[30]
Cytochrome P450 2C9 (CYP2C9)	OTGLBN29	CP2C9_HUMAN	Decreases Response To Substance	[31]
Apolipoprotein B-100 (APOB)	OTH0UOCZ	APOB_HUMAN	Affects Response To Substance	[32]
Cytochrome P450 11B2, mitochondrial (CYP11B2)	OTIOLWYN	C11B2_HUMAN	Increases Response To Substance	[33]
B2 bradykinin receptor (BDKRB2)	OTOA9D3W	BKRB2_HUMAN	Affects Response To Substance	[34]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Affects Response To Substance	[35]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Affects Response To Substance	[36]
Endothelin-1 (EDN1)	OTZCACEG	EDN1_HUMAN	Affects Response To Substance	[37]

References

• [1] ClinicalTrials.gov (NCT00660309) A Clinical Study to Evaluate Renal Hemodynamic Responses to Aliskiren in Patients With Type 2 Diabetes Mellitus
• [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] Irbesartan FDA Label
• [6] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 203534.
• [7] Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001 Sep 20;345(12):851-60. Clinical Trial
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