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]
• 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]
Benazepril	DMH1M9B	Hypertension	BA00-BA04	Approved	[3]
Captopril	DM458UM	Chronic heart failure	BD1Z	Approved	[4]
Cilazapril	DM4V6JA	Congestive heart failure	BD10	Approved	[5]
Delapril	DM7EUK3	Cardiovascular disease	BA00-BE2Z	Approved	[2]
Deserpidine	DMRH7CV	Hypertension	BA00-BA04	Approved	[1]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[6]
Enalaprilat	DMFYAM1	Congestive heart failure	BD10	Approved	[7]
Fosinopril	DM9NJ52	Chronic heart failure	BD1Z	Approved	[8]
Hydrochlorothiazide	DMUSZHD	Chronic heart failure	BD1Z	Approved	[9]
Imidapril	DMUL7T1	Cardiovascular disease	BA00-BE2Z	Approved	[2]
Lisinopril	DMUOK4C	Chronic heart failure	BD1Z	Approved	[10]
Moexipril	DM26E4B	Hypertension	BA00-BA04	Approved	[11]
Perindopril	DMOPZDT	Hypertension	BA00-BA04	Approved	[12]
Quinapril	DMR8H31	Chronic heart failure	BD1Z	Approved	[13]
Ramipril	DM2R68E	Acute heart failure	BD10-BD13	Approved	[14]
Rescinnamine	DMG7SQK	Hypertension	BA00-BA04	Approved	[15]
Spirapril	DM5XLTY	Hypertension	BA00-BA04	Approved	[16]
Temocapril hydrochloride	DM0JXFL	Cardiovascular disease	BA00-BE2Z	Approved	[2]
Trandolapril	DM4L6EU	Chronic heart failure	BD1Z	Approved	[17]

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	[18]
Gallopamil	DMXBR27	Asthma	CA23	Phase 2	[19]
GW-796406	DMQ46DN	Hypotension	BA20-BA21	Phase 1	[19]

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	[20]
Ceronapril	DMFBNI6	Major depressive disorder	6A70.3	Discontinued in Phase 2	[21]
Idrapril	DM7O0UR	Hypertension	BA00-BA04	Discontinued in Phase 2	[22]
M-100240	DMQ1LWU	Hypotension	BA20-BA21	Discontinued in Phase 2	[23]
METIAPRIL	DM90SHY	Hypotension	BA20-BA21	Discontinued in Phase 2	[24]
UTIBAPRIL	DMOB2K5	Hypertension	BA00-BA04	Discontinued in Phase 2	[25]
Zabiciprilat	DMBSHJ6	Hypertension	BA00-BA04	Discontinued in Phase 2	[26]
BMS-182657	DM0K4DZ	Cardiovascular disease	BA00-BE2Z	Terminated	[27]
CGS-30440	DM94WIO	Hypertension	BA00-BA04	Terminated	[28]
DU-1777	DM87ZWP	Hypertension	BA00-BA04	Terminated	[29]
GW-660511	DMG5A1Z	Hypertension	BA00-BA04	Terminated	[30]
Omapatrilat	DMAGUY0	Hypertension	BA00-BA04	Terminated	[31]
SCH-54470	DMEWLZ7	N. A.	N. A.	Terminated	[32]
SQ-26332	DM6SW2R	N. A.	N. A.	Terminated	[33]

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	[34]
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[34]
ASTRAGALIN	DMZHWPG	Discovery agent	N.A.	Investigative	[18]
BRL-36378	DMRI49D	Discovery agent	N.A.	Investigative	[35]
BUTEIN	DM8E54P	Discovery agent	N.A.	Investigative	[36]
fasidotrilat	DMC8G7X	Discovery agent	N.A.	Investigative	[37]
Kaempferol-3-O-(2''-O-galloyl)-glucoside	DMUCZ3F	Discovery agent	N.A.	Investigative	[18]
lisinopril-tryptophan	DMQ42KU	Discovery agent	N.A.	Investigative	[38]
LY-292223	DML36ZE	Discovery agent	N.A.	Investigative	[39]
moexiprilat	DMPYBHI	Discovery agent	N.A.	Investigative	[40]
N-Carboxymethyl-N-cyclopentyl-phthalamic acid	DME9U7Y	Discovery agent	N.A.	Investigative	[41]
RB-105	DMRK3HO	Hypertension	BA00-BA04	Investigative	[42]
RIP	DM83L5Y	Discovery agent	N.A.	Investigative	[43]
RJM-0035-K002	DM2P6I8	Hypertension	BA00-BA04	Investigative	[44]
RXP-407	DMM5O30	Discovery agent	N.A.	Investigative	[45]
[Cyclopentyl-(2-nitro-benzoyl)-amino]-acetic acid	DMQ8CD3	Discovery agent	N.A.	Investigative	[41]

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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