Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM5XLTY)

• Drug Name: Spirapril Drug Info
• Synonyms: Renormax; Sandopril; Setrilan; Espirapril [Spanish]; Not established; Spiraprilum [Latin]; Sch-33844; Spirapril (INN); Spirapril [INN:BAN]; TI-211-950; (2S)-3-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]-6,9-dithia-3-azaspiro[4.4]nonane-2-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Approved	[1]

• Therapeutic Class: Antihypertensive Agents
• Cross-matching ID:
  PubChem CID: 5311447
  ChEBI ID: CHEBI:135756
  CAS Number: CAS 83647-97-6
  TTD Drug ID: DM5XLTY
  VARIDT Drug ID: DR00095
  INTEDE Drug ID: DR2730

Molecule-Related Drug Atlas

Drug(s) Targeting Angiotensin-converting enzyme (ACE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[5]
Captopril	DM458UM	Chronic heart failure	BD1Z	Approved	[6]
Benazepril	DMH1M9B	Hypertension	BA00-BA04	Approved	[7]
Moexipril	DM26E4B	Hypertension	BA00-BA04	Approved	[8]
Ramipril	DM2R68E	Acute heart failure	BD10-BD13	Approved	[9]
Perindopril	DMOPZDT	Hypertension	BA00-BA04	Approved	[10]
Trandolapril	DM4L6EU	Chronic heart failure	BD1Z	Approved	[11]
Fosinopril	DM9NJ52	Chronic heart failure	BD1Z	Approved	[12]
Lisinopril	DMUOK4C	Chronic heart failure	BD1Z	Approved	[13]
Enalaprilat	DMFYAM1	Congestive heart failure	BD10	Approved	[14]

Drug(s) Transported By Peptide transporter 1 (SLC15A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[15]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[16]
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[17]
Losartan	DM72JXH	Diabetic kidney disease	GB61.Z	Approved	[18]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[19]
Cefazolin	DMPDYFR	Bacteremia	1A73	Approved	[20]
Ceftriaxone	DMCEW64	Acute gonococcal cervicitis		Approved	[21]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[16]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[18]
Irbesartan	DMTP1DC	Diabetic kidney disease	GB61.Z	Approved	[18]

Drug(s) Transported By Peptide transporter 2 (SLC15A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[15]
Ampicillin	DMHWE7P	Acute epiglottitis		Approved	[22]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[23]
Entecavir	DM7VTQO	Hepatitis B virus infection	1E51.0	Approved	[24]
Cefadroxil	DMMC345	Bacterial infection	1A00-1C4Z	Approved	[25]
Cephalexin	DMD5JU8	Acute otitis media	AB00	Approved	[22]
Valaciclovir	DMHKS94	Genital herpes	1A94	Approved	[26]
Cefaclor	DMJXDGC	Bacterial infection	1A00-1C4Z	Approved	[15]
Aminolevulinic acid hci	DMS4BLQ	Acne vulgaris	ED80	Approved	[27]
Cefixime	DMY60I8	Acute gonococcal cervicitis		Approved	[22]

Drug(s) Metabolized By Dipeptidase (pepV)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[4]
Enalaprilat	DMFYAM1	Congestive heart failure	BD10	Approved	[4]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Angiotensin-converting enzyme (ACE)	TTL69WB	ACE_HUMAN	Inhibitor	[2]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Peptide transporter 2 (SLC15A2)	DT8QKNP	S15A2_HUMAN	Substrate	[3]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Dipeptidase (pepV) Main DME	DEQMBHW	Q84BU9_LACLH	Substrate	[4]

References

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• [2] Central angiotensin II controls alcohol consumption via its AT1 receptor. FASEB J. 2005 Sep;19(11):1474-81.
• [3] Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41.
• [4] Characterization and kinetic analysis of enzyme-substrate recognition by three recombinant lactococcal PepVs. Arch Biochem Biophys. 2006 Oct 15;454(2):137-45.
• [5] Determination of bezafibrate, methotrexate, cyclophosphamide, orlistat and enalapril in waste and surface waters using on-line solid-phase extracti... J Environ Monit. 2009 Apr;11(4):830-8.
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• [8] Moexipril for treatment of primary biliary cirrhosis in patients with an incomplete response to ursodeoxycholic acid. Dig Dis Sci. 2010 Feb;55(2):476-83.
• [9] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [10] Fixed combination perindopril-amlodipine (Coveram) in the treatment of hypertension and coronary heart disease. Rev Med Liege. 2009 Apr;64(4):223-7.
• [11] Selective reduction of central pulse pressure under angiotensin blockage in SHR: role of the fibronectin-alpha5beta1 integrin complex. Am J Hypertens. 2009 Jul;22(7):711-7.
• [12] Angiotensin-converting enzyme inhibition and novel cardiovascular risk biomarkers: results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study. Am Heart J. 2009 Feb;157(2):334.e1-8.
• [13] Involvement of vascular angiotensin II-forming enzymes in the progression of aortic abdominal aneurysms in angiotensin II- infused ApoE-deficient m... J Atheroscler Thromb. 2009 Jun;16(3):164-71.
• [14] Analysis of Vancomycin in the Hindlimb Vascular Bed of the Rat. Am J Ther. 1996 Oct;3(10):681-687.
• [15] Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos. 2006 Apr;34(4):547-55.
• [16] Peptide transporter substrate identification during permeability screening in drug discovery: comparison of transfected MDCK-hPepT1 cells to Caco-2 cells. Arch Pharm Res. 2007 Apr;30(4):507-18.
• [17] Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR. Res Microbiol. 2017 Jun;168(5):443-449.
• [18] High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos. 2009 Jan;37(1):143-9.
• [19] The intestinal H+/peptide symporter PEPT1: structure-affinity relationships. Eur J Pharm Sci. 2004 Jan;21(1):53-60.
• [20] Three-dimensional quantitative structure-activity relationship analyses of beta-lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide cotransporter PEPT1. J Med Chem. 2005 Jun 30;48(13):4410-9.
• [21] Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm Res. 1999 Jan;16(1):55-61.
• [22] Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives. J Pharmacol Exp Ther. 2006 Jul;318(1):455-60.
• [23] Ethanol inhibits functional activity of the human intestinal dipeptide transporter hPepT1 expressed in Xenopus oocytes. Alcohol Clin Exp Res. 2008 May;32(5):777-84.
• [24] The oligopeptide transporter 2-mediated reabsorption of entecavir in rat kidney. Eur J Pharm Sci. 2014 Feb 14;52:41-7.
• [25] Species Differences in Human and Rodent PEPT2-Mediated Transport of Glycylsarcosine and Cefadroxil in Pichia Pastoris Transformants. Drug Metab Dispos. 2017 Feb;45(2):130-136.
• [26] Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun. 1998 May 19;246(2):470-5.
• [27] PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes. Brain Res. 2006 Nov 29;1122(1):18-23.