Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTL69WB)

• DTT Name: Angiotensin-converting enzyme (ACE)
• Synonyms: Kininase II; Dipeptidyl carboxypeptidase I; DCP1; DCP; CD143 antigen; CD143; ACE
• Gene Name: SLC33A1
• DTT Type: Successful target; [1]
• Related Disease:
  Cardiovascular disease [ICD-11: BA00-BE2Z]
  Heart failure [ICD-11: BD10-BD1Z]
  Hypertension [ICD-11: BA00-BA04]
• BioChemical Class: Glycosylase
• UniProt ID: ACE_HUMAN
• TTD ID: T82577
• EC Number: EC 3.2.1.-
• Sequence:
  MGAASGRRGPGLLLPLPLLLLLPPQPALALDPGLQPGNFSADEAGAQLFAQSYNSSAEQV
  LFQSVAASWAHDTNITAENARRQEEAALLSQEFAEAWGQKAKELYEPIWQNFTDPQLRRI
  IGAVRTLGSANLPLAKRQQYNALLSNMSRIYSTAKVCLPNKTATCWSLDPDLTNILASSR
  SYAMLLFAWEGWHNAAGIPLKPLYEDFTALSNEAYKQDGFTDTGAYWRSWYNSPTFEDDL
  EHLYQQLEPLYLNLHAFVRRALHRRYGDRYINLRGPIPAHLLGDMWAQSWENIYDMVVPF
  PDKPNLDVTSTMLQQGWNATHMFRVAEEFFTSLELSPMPPEFWEGSMLEKPADGREVVCH
  ASAWDFYNRKDFRIKQCTRVTMDQLSTVHHEMGHIQYYLQYKDLPVSLRRGANPGFHEAI
  GDVLALSVSTPEHLHKIGLLDRVTNDTESDINYLLKMALEKIAFLPFGYLVDQWRWGVFS
  GRTPPSRYNFDWWYLRTKYQGICPPVTRNETHFDAGAKFHVPNVTPYIRYFVSFVLQFQF
  HEALCKEAGYEGPLHQCDIYRSTKAGAKLRKVLQAGSSRPWQEVLKDMVGLDALDAQPLL
  KYFQPVTQWLQEQNQQNGEVLGWPEYQWHPPLPDNYPEGIDLVTDEAEASKFVEEYDRTS
  QVVWNEYAEANWNYNTNITTETSKILLQKNMQIANHTLKYGTQARKFDVNQLQNTTIKRI
  IKKVQDLERAALPAQELEEYNKILLDMETTYSVATVCHPNGSCLQLEPDLTNVMATSRKY
  EDLLWAWEGWRDKAGRAILQFYPKYVELINQAARLNGYVDAGDSWRSMYETPSLEQDLER
  LFQELQPLYLNLHAYVRRALHRHYGAQHINLEGPIPAHLLGNMWAQTWSNIYDLVVPFPS
  APSMDTTEAMLKQGWTPRRMFKEADDFFTSLGLLPVPPEFWNKSMLEKPTDGREVVCHAS
  AWDFYNGKDFRIKQCTTVNLEDLVVAHHEMGHIQYFMQYKDLPVALREGANPGFHEAIGD
  VLALSVSTPKHLHSLNLLSSEGGSDEHDINFLMKMALDKIAFIPFSYLVDQWRWRVFDGS
  ITKENYNQEWWSLRLKYQGLCPPVPRTQGDFDPGAKFHIPSSVPYIRYFVSFIIQFQFHE
  ALCQAAGHTGPLHKCDIYQSKEAGQRLATAMKLGFSRPWPEAMQLITGQPNMSASAMLSY
  FKPLLDWLRTENELHGEKLGWPQYNWTPNSARSEGPLPDSGRVSFLGLDLDAQQARVGQW
  LLLFLGIALLVATLGLSQRLFSIRHRSLHRHSHGPQFGSEVELRHS
• Function: Able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin.
• KEGG Pathway:
  Renin-angiotensin system (hsa04614)
  Chagas disease (American trypanosomiasis) (hsa05142)
  Hypertrophic cardiomyopathy (HCM) (hsa05410)
• Reactome Pathway: Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377)
• BioCyc Pathway: MetaCyc:HS08412-MON

Molecular Interaction Atlas (MIA) of This DTT

20 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alacepril	DML6SRO	Cardiovascular disease	BA00-BE2Z	Approved	[2], [3]
Benazepril	DMH1M9B	Hypertension	BA00-BA04	Approved	[4], [5]
Captopril	DM458UM	Hypertension	BA00-BA04	Approved	[6]
Cilazapril	DM4V6JA	Congestive heart failure	BD10	Approved	[7]
Delapril	DM7EUK3	Cardiovascular disease	BA00-BE2Z	Approved	[2], [3], [8], [9]
Deserpidine	DMRH7CV	Hypertension	BA00-BA04	Approved	[1], [10]
Enalapril	DMNFUZR	Hypertension	BA00-BA04	Approved	[11]
Enalaprilat	DMPRBQV	Hypertension	BA00-BA04	Approved	[12]
Fosinopril	DM9NJ52	Hypertension	BA00-BA04	Approved	[13]
Hydrochlorothiazide	DMUSZHD	Hypertension	BA00-BA04	Approved	[14]
Imidapril	DMUL7T1	Cardiovascular disease	BA00-BE2Z	Approved	[2], [3]
Lisinopril	DMUOK4C	Hypertension	BA00-BA04	Approved	[15]
Moexipril	DM26E4B	Hypertension	BA00-BA04	Approved	[16]
Perindopril	DMOPZDT	Hypertension	BA00-BA04	Approved	[17]
Quinapril	DMR8H31	Hypertension	BA00-BA04	Approved	[18]
Ramipril	DM2R68E	Congestive heart failure	BD10	Approved	[5]
Rescinnamine	DMG7SQK	Hypertension	BA00-BA04	Approved	[19]
Spirapril	DM5XLTY	Hypertension	BA00-BA04	Approved	[20]
Temocapril hydrochloride	DM0JXFL	Cardiovascular disease	BA00-BE2Z	Approved	[2], [3]
Trandolapril	DM4L6EU	Hypertension	BA00-BA04	Approved	[21]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Contigoside B	DMX9V8K	Thrombosis	DB61-GB90	Phase 2/3	[22]
Gallopamil	DMXBR27	Asthma	CA23	Phase 2	[23]
GW-796406	DMQ46DN	Hypotension	BA20-BA21	Phase 1	[23]

14 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ilepatril	DMTR50E	Diabetic nephropathy	GB61.Z	Discontinued in Phase 2/3	[24]
Ceronapril	DMFBNI6	Major depressive disorder	6A70.3	Discontinued in Phase 2	[25]
Idrapril	DM7O0UR	Hypertension	BA00-BA04	Discontinued in Phase 2	[26]
M-100240	DMQ1LWU	Hypotension	BA20-BA21	Discontinued in Phase 2	[27], [28]
METIAPRIL	DM90SHY	Hypotension	BA20-BA21	Discontinued in Phase 2	[29]
UTIBAPRIL	DMOB2K5	Hypertension	BA00-BA04	Discontinued in Phase 2	[30]
Zabiciprilat	DMBSHJ6	Hypertension	BA00-BA04	Discontinued in Phase 2	[31]
BMS-182657	DM0K4DZ	Cardiovascular disease	BA00-BE2Z	Terminated	[32]
CGS-30440	DM94WIO	Hypertension	BA00-BA04	Terminated	[33]
DU-1777	DM87ZWP	Hypertension	BA00-BA04	Terminated	[34]
GW-660511	DMG5A1Z	Hypertension	BA00-BA04	Terminated	[35]
Omapatrilat	DMAGUY0	Hypertension	BA00-BA04	Terminated	[36]
SCH-54470	DMEWLZ7	N. A.	N. A.	Terminated	[37]
SQ-26332	DM6SW2R	N. A.	N. A.	Terminated	[38]

16 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-(Acetylamino)-2-Deoxy-a-D-Glucopyranose	DMOUG6Y	Discovery agent	N.A.	Investigative	[39]
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[39]
ASTRAGALIN	DMZHWPG	Discovery agent	N.A.	Investigative	[22]
BRL-36378	DMRI49D	Discovery agent	N.A.	Investigative	[40]
BUTEIN	DM8E54P	Discovery agent	N.A.	Investigative	[41]
fasidotrilat	DMC8G7X	Discovery agent	N.A.	Investigative	[42]
Kaempferol-3-O-(2''-O-galloyl)-glucoside	DMUCZ3F	Discovery agent	N.A.	Investigative	[22]
lisinopril-tryptophan	DMQ42KU	Discovery agent	N.A.	Investigative	[43]
LY-292223	DML36ZE	Discovery agent	N.A.	Investigative	[44]
moexiprilat	DMPYBHI	Discovery agent	N.A.	Investigative	[45], [46]
N-Carboxymethyl-N-cyclopentyl-phthalamic acid	DME9U7Y	Discovery agent	N.A.	Investigative	[47]
RB-105	DMRK3HO	Hypertension	BA00-BA04	Investigative	[48], [49], [50]
RIP	DM83L5Y	Discovery agent	N.A.	Investigative	[51]
RJM-0035-K002	DM2P6I8	Hypertension	BA00-BA04	Investigative	[52]
RXP-407	DMM5O30	Discovery agent	N.A.	Investigative	[53]
[Cyclopentyl-(2-nitro-benzoyl)-amino]-acetic acid	DMQ8CD3	Discovery agent	N.A.	Investigative	[47]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Major depressive disorder	6A20	Pre-frontal cortex	2.62E-01	-0.01	-0.06

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