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

General Information of Drug (ID: DMEWLZ7)

• Drug Name: SCH-54470 Drug Info
• Synonyms: CHEMBL43370; SCH-54470; BDBM50287430; (S)-2-[(1-{[(R)-1-((S)-6-Amino-2-methanesulfonylamino-hexanoylamino)-2-phenyl-ethyl]-hydroxy-phosphinoylmethyl}-cyclopentanecarbonyl)-amino]-3-(1H-indol-3-yl)-propionic acid
• Cross-matching ID:
  PubChem CID: 9810328
  TTD Drug ID: DMEWLZ7

Molecule-Related Drug Atlas

Drug(s) Targeting Neutral endopeptidase (MME)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LCZ696	DMLFX7K	Heart failure	BD10-BD13	Approved	[2]
Candoxatril	DMHJCGV	Hypertension	BA00-BA04	Phase 3	[3]
Gallopamil	DMXBR27	Asthma	CA23	Phase 2	[4]
SLV 306	DMCDON3	Acute decompensated heart failure	BD1Z	Phase 2	[5]
SLV-334	DMXCJKY	Brain injury	NA07.Z	Phase 2	[6]
VX-15	DMLWM4G	Huntington disease	8A01.10	Phase 2	[7]
Sampatrilat	DMXTOVE	Hypotension	BA20-BA21	Phase 2	[8]
SLV-338	DM7WKTM	Cardiovascular disease	BA00-BE2Z	Phase 1	[9]
GW-796406	DMQ46DN	Hypotension	BA20-BA21	Phase 1	[4]
Debio 0827	DMQIEFB	Chronic pain	MG30	Phase 1	[10]

Drug(s) Targeting Endothelin-converting enzyme 1 (ECE1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY-292223	DML36ZE	Discovery agent	N.A.	Investigative	[11]
CGS 35066	DMCHT27	Discovery agent	N.A.	Investigative	[12]
PO3 2-Nle-Trp-O-3K	DMW1XY4	Discovery agent	N.A.	Investigative	[13]
PMID19899765C22	DMBTV20	Discovery agent	N.A.	Investigative	[1]
PO3 2-Leu-Trp-O-3K	DM3O78D	Discovery agent	N.A.	Investigative	[13]
5-(2-hydroxyethyl)nonane-1,9-diol	DMHBD1T	Discovery agent	N.A.	Investigative	[14]
PO3 2-Ile-Trp-O-3K	DMQMDSG	Discovery agent	N.A.	Investigative	[13]
PD159790	DM6RVTO	Discovery agent	N.A.	Investigative	[15]
PO3 2-Leu-Nal-O-3K	DMY43FU	Discovery agent	N.A.	Investigative	[13]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[16]
Spirapril	DM5XLTY	Hypertension	BA00-BA04	Approved	[17]
Captopril	DM458UM	Chronic heart failure	BD1Z	Approved	[18]
Benazepril	DMH1M9B	Hypertension	BA00-BA04	Approved	[19]
Moexipril	DM26E4B	Hypertension	BA00-BA04	Approved	[20]
Ramipril	DM2R68E	Acute heart failure	BD10-BD13	Approved	[21]
Perindopril	DMOPZDT	Hypertension	BA00-BA04	Approved	[22]
Trandolapril	DM4L6EU	Chronic heart failure	BD1Z	Approved	[23]
Fosinopril	DM9NJ52	Chronic heart failure	BD1Z	Approved	[24]
Lisinopril	DMUOK4C	Chronic heart failure	BD1Z	Approved	[25]

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	[1]
Endothelin-converting enzyme 1 (ECE1)	TTQ9RYT	ECE1_HUMAN	Inhibitor	[1]
Neutral endopeptidase (MME)	TT5TKPM	NEP_HUMAN	Inhibitor	[1]

References

• [1] Phosphinic tripeptides as dual angiotensin-converting enzyme C-domain and endothelin-converting enzyme-1 inhibitors. J Med Chem. 2010 Jan 14;53(1):208-20.
• [2] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [3] Neutral endopeptidase inhibitor suppresses the early phase of atrial electrical remodeling in a canine rapid atrial pacing model. Indian Pacing Electrophysiol J. 2008 Apr 1;8(2):102-13.
• [4] Mechanism of vasopeptidase inhibitor-induced plasma extravasation: comparison of omapatrilat and the novel neutral endopeptidase 24.11/angiotensin-converting enzyme inhibitor GW796406. J Pharmacol Exp Ther. 2005 Dec;315(3):1306-13.
• [5] The dual endothelin converting enzyme/neutral endopeptidase inhibitor SLV-306 (daglutril), inhibits systemic conversion of big endothelin-1 in humans. Life Sci. 2012 Oct 15;91(13-14):743-8.
• [6] Clinical trials in traumatic brain injury: past experience and current developments.Neurotherapeutics.2010 Jan;7(1):115-26.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Sustained antihypertensive actions of a dual angiotensin-converting enzyme neutral endopeptidase inhibitor, sampatrilat, in black hypertensive subjects. Am J Hypertens. 1999 Jun;12(6):563-71.
• [9] Renoprotective effects of combined endothelin-converting enzyme/neutral endopeptidase inhibitor SLV338 in acute and chronic experimental renal damage. Clin Lab. 2011;57(7-8):507-15.
• [10] Clinical pipeline report, company report or official report of Debiopharm (2011).
• [11] Endothelin-converting enzyme-1 inhibition and growth of human glioblastoma cells. J Med Chem. 2005 Jan 27;48(2):483-98.
• [12] The therapeutic potential of endothelin-1 receptor antagonists and endothelin-converting enzyme inhibitors on the cardiovascular system. Expert Opin Investig Drugs. 2002 Nov;11(11):1537-52.
• [13] Aminophosphonate endothelin converting enzyme inhibitors: potency-enhancing and selectivity-improving modifications of phosphoramidon, Bioorg. Med. Chem. Lett. 4(10):1257-1262 (1994).
• [14] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [15] 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. (Target id: 1615).
• [16] 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.
• [17] Central angiotensin II controls alcohol consumption via its AT1 receptor. FASEB J. 2005 Sep;19(11):1474-81.
• [18] Using ACE inhibitors appropriately. Am Fam Physician. 2002 Aug 1;66(3):461-8.
• [19] Efficacy of benazepril hydrochloride to delay the progression of occult dilated cardiomyopathy in Doberman Pinschers. J Vet Intern Med. 2009 Sep-Oct;23(5):977-83.
• [20] 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.
• [21] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [22] Fixed combination perindopril-amlodipine (Coveram) in the treatment of hypertension and coronary heart disease. Rev Med Liege. 2009 Apr;64(4):223-7.
• [23] 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.
• [24] 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.
• [25] 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.