Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Aminopeptidase N (ANPEP)
• Synonyms: Myeloid plasma membrane glycoprotein CD13; Microsomal aminopeptidase; HAPN; Gp150; Aminopeptidase M; Alanyl aminopeptidase; ANPEP
• Gene Name: ANPEP
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Peptidase
• UniProt ID: AMPN_HUMAN
• TTD ID: T67272
• EC Number: EC 3.4.11.2
• Sequence:
  MAKGFYISKSLGILGILLGVAAVCTIIALSVVYSQEKNKNANSSPVASTTPSASATTNPA
  SATTLDQSKAWNRYRLPNTLKPDSYRVTLRPYLTPNDRGLYVFKGSSTVRFTCKEATDVI
  IIHSKKLNYTLSQGHRVVLRGVGGSQPPDIDKTELVEPTEYLVVHLKGSLVKDSQYEMDS
  EFEGELADDLAGFYRSEYMEGNVRKVVATTQMQAADARKSFPCFDEPAMKAEFNITLIHP
  KDLTALSNMLPKGPSTPLPEDPNWNVTEFHTTPKMSTYLLAFIVSEFDYVEKQASNGVLI
  RIWARPSAIAAGHGDYALNVTGPILNFFAGHYDTPYPLPKSDQIGLPDFNAGAMENWGLV
  TYRENSLLFDPLSSSSSNKERVVTVIAHELAHQWFGNLVTIEWWNDLWLNEGFASYVEYL
  GADYAEPTWNLKDLMVLNDVYRVMAVDALASSHPLSTPASEINTPAQISELFDAISYSKG
  ASVLRMLSSFLSEDVFKQGLASYLHTFAYQNTIYLNLWDHLQEAVNNRSIQLPTTVRDIM
  NRWTLQMGFPVITVDTSTGTLSQEHFLLDPDSNVTRPSEFNYVWIVPITSIRDGRQQQDY
  WLIDVRAQNDLFSTSGNEWVLLNLNVTGYYRVNYDEENWRKIQTQLQRDHSAIPVINRAQ
  IINDAFNLASAHKVPVTLALNNTLFLIEERQYMPWEAALSSLSYFKLMFDRSEVYGPMKN
  YLKKQVTPLFIHFRNNTNNWREIPENLMDQYSEVNAISTACSNGVPECEEMVSGLFKQWM
  ENPNNNPIHPNLRSTVYCNAIAQGGEEEWDFAWEQFRNATLVNEADKLRAALACSKELWI
  LNRYLSYTLNPDLIRKQDATSTIISITNNVIGQGLVWDFVQSNWKKLFNDYGGGSFSFSN
  LIQAVTRRFSTEYELQQLEQFKKDNEETGFGSGTRALEQALEKTKANIKWVKENKEVVLQ
  WFTENSK
• Function: Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. May play a critical role in the pathogenesis of cholesterol gallstone disease. May be involved in the metabolism of regulatory peptides of diverse cell types, responsible for the processing of peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines. Found to cleave antigen peptides bound to major histocompatibility complex class II molecules of presenting cells and to degrade neurotransmitters at synaptic junctions. Is also implicated as a regulator of IL-8 bioavailability in the endometrium, and therefore may contribute to the regulation of angiogenesis. Is used as a marker for acute myeloid leukemia and plays a role in tumor invasion. In case of human coronavirus 229E (HCoV-229E) infection, serves as receptor for HCoV-229E spike glycoprotein. Mediates as well human cytomegalovirus (HCMV) infection.
• KEGG Pathway:
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)
  Renin-angiotensin system (hsa04614)
  Hematopoietic cell lineage (hsa04640)
• Reactome Pathway: Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IP10 C8	DMANRGW	Psoriasis vulgaris	EA90	Phase 2	[1]

39 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(1-Amino-2-phenyl-ethyl)-phosphinic acid	DMXD8H1	Discovery agent	N.A.	Investigative	[2]
(1-Amino-3-methyl-butyl)-phosphinic acid	DMNUO79	Discovery agent	N.A.	Investigative	[2]
(1-Amino-3-methylsulfanyl-propyl)-phosphinic acid	DMJL8QZ	Discovery agent	N.A.	Investigative	[2]
(1-Amino-3-phenyl-propyl)-phosphinic acid	DMXD697	Discovery agent	N.A.	Investigative	[2]
(1-Amino-ethyl)-phosphinic acid	DMUACZF	Discovery agent	N.A.	Investigative	[2]
(Amino-phenyl-methyl)-phosphinic acid	DMS4ZVK	Discovery agent	N.A.	Investigative	[2]
(S)-2-Amino-2-phenyl-ethanethiol	DMFEGPX	Discovery agent	N.A.	Investigative	[2]
(S)-2-Amino-3-phenyl-propane-1-thiol	DMMAUKO	Discovery agent	N.A.	Investigative	[2]
(S)-2-Amino-4-methyl-pentane-1-thiol	DM96XYI	Discovery agent	N.A.	Investigative	[2]
(S)-2-Amino-4-methylsulfanyl-butane-1-thiol	DMOVQ1T	Discovery agent	N.A.	Investigative	[2]
(S)-2-Amino-4-phenyl-butane-1-thiol	DMJEGMI	Discovery agent	N.A.	Investigative	[2]
(S)-2-Amino-propane-1-thiol	DMYG8EV	Discovery agent	N.A.	Investigative	[2]
1-aminobutylphosphonic acid	DM4TFN6	Discovery agent	N.A.	Investigative	[3]
1-aminohexylphosphonic acid	DMFUABI	Discovery agent	N.A.	Investigative	[3]
1-aminohexylphosphonic acid monophenyl ester	DML6UJM	Discovery agent	N.A.	Investigative	[3]
1-aminopentylphosphonic acid monophenyl ester	DMMV30B	Discovery agent	N.A.	Investigative	[3]
2-amino-N1-benzyl-N3-hydroxymalonamide	DMQ30UY	Discovery agent	N.A.	Investigative	[4]
2-benzyl-N1-hydroxy-N3-(3-phenylpropyl)malonamide	DMF5MGQ	Discovery agent	N.A.	Investigative	[4]
2-benzyl-N1-hydroxy-N3-(4-phenylbutyl)malonamide	DMRVA94	Discovery agent	N.A.	Investigative	[4]
2-benzyl-N1-hydroxy-N3-phenethylmalonamide	DM2BPIN	Discovery agent	N.A.	Investigative	[4]
2-Cinnamamido-N1-hydroxy-N4-octylsuccinamide	DMXYTGU	Discovery agent	N.A.	Investigative	[5]
2-Cinnamamido-N1-hydroxy-N4-pentylsuccinamide	DMI6FZN	Discovery agent	N.A.	Investigative	[5]
2-Cinnamamido-N4-hexyl-N1-hydroxysuccinamide	DMRNGK7	Discovery agent	N.A.	Investigative	[5]
Angiotensin IV	DMR9OD1	Discovery agent	N.A.	Investigative	[6]
KELATORPHAN	DMOX8FD	Discovery agent	N.A.	Investigative	[7]
N-biphenyl-3-ylmethyl-N'-hydroxy-malonamide	DMJF9VA	Discovery agent	N.A.	Investigative	[4]
N-Hydroxy-2-(naphthalen-2-ylsulfanyl)-acetamide	DMISXUM	Discovery agent	N.A.	Investigative	[8]
N1,2-dibenzyl-N3-hydroxy-N1-phenethylmalonamide	DM1L89K	Discovery agent	N.A.	Investigative	[4]
N1,2-dibenzyl-N3-hydroxymalonamide	DMM59IS	Discovery agent	N.A.	Investigative	[4]
N1-(3,3-diphenylpropyl)-N3-hydroxymalonamide	DM5F04D	Discovery agent	N.A.	Investigative	[4]
N1-(3-phenoxybenzyl)-N3-hydroxymalonamide	DMSRHJA	Discovery agent	N.A.	Investigative	[4]
N1-(4-chlorobenzyl)-2-amino-N3-hydroxymalonamide	DMJ025O	Discovery agent	N.A.	Investigative	[4]
N1-(4-chlorobenzyl)-2-benzyl-N3-hydroxymalonamide	DMTMDZ4	Discovery agent	N.A.	Investigative	[4]
N1-(4-fluorobenzyl)-2-benzyl-N3-hydroxymalonamide	DMS1P85	Discovery agent	N.A.	Investigative	[4]
N1-benzyl-N3-hydroxy-2-isobutylmalonamide	DMXSFWK	Discovery agent	N.A.	Investigative	[9]
N1-hydroxy-2-isobutyl-N3-phenethylmalonamide	DMF6RVS	Discovery agent	N.A.	Investigative	[9]
N4-Butyl-2-cinnamamido-N1-hydroxysuccinamide	DM1N73J	Discovery agent	N.A.	Investigative	[5]
PMID23428964CI3	DMZUQ7X	Discovery agent	N.A.	Investigative	[10]
[(125)I] RB129	DMX0G7E	Discovery agent	N.A.	Investigative	[11]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Psoriasis	EA90	Skin	8.84E-07	-0.3	-0.71

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Alanyl aminopeptidase (ANPEP) DME Info
• Gene Name: ANPEP

1 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Human calcitonin	DM0WD1V	N. A.	N. A.	Phase 4	[12]

References

• [1] Recent insights into the role of dipeptidyl aminopeptidase IV (DPIV) and aminopeptidase N (APN) families in immune functions. Clin Chem Lab Med. 2009;47(3):253-61.
• [2] Design of the first highly potent and selective aminopeptidase N (EC 3.4.11.2) inhibitor. Bioorg Med Chem Lett. 1999 Jun 7;9(11):1511-6.
• [3] New aromatic monoesters of alpha-aminoaralkylphosphonic acids as inhibitors of aminopeptidase N/CD13. Bioorg Med Chem. 2010 Apr 15;18(8):2930-6.
• [4] Novel selective inhibitors of the zinc plasmodial aminopeptidase PfA-M1 as potential antimalarial agents. J Med Chem. 2007 Mar 22;50(6):1322-34.
• [5] Design, synthesis, and preliminary studies of the activity of novel derivatives of N-cinnamoyl-L-aspartic acid as inhibitors of aminopeptidase N/CD13. Bioorg Med Chem. 2009 Oct 15;17(20):7398-404.
• [6] Ligands to the (IRAP)/AT4 receptor encompassing a 4-hydroxydiphenylmethane scaffold replacing Tyr2. Bioorg Med Chem. 2008 Jul 15;16(14):6924-35.
• [7] Retro-inverso concept applied to the complete inhibitors of enkephalin-degrading enzymes. J Med Chem. 1988 Sep;31(9):1825-31.
• [8] N-hydroxy-2-(naphthalene-2-ylsulfanyl)-acetamide, a novel hydroxamic acid-based inhibitor of aminopeptidase N and its anti-angiogenic activity. Bioorg Med Chem Lett. 2005 Jan 3;15(1):181-3.
• [9] A library of novel hydroxamic acids targeting the metallo-protease family: design, parallel synthesis and screening. Bioorg Med Chem. 2007 Jan 1;15(1):63-76.
• [10] Selective aminopeptidase-N (CD13) inhibitors with relevance to cancer chemotherapy. Bioorg Med Chem. 2013 Apr 1;21(7):2135-44.
• [11] Ontogenic and adult whole body distribution of aminopeptidase N in rat investigated by in vitro autoradiography. Biochimie. 2004 Feb;86(2):105-13.
• [12] Renal metabolism of calcitonin. Am J Physiol. 1988 Apr;254(4 Pt 2):F593-600.