Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7HC21)

• DTT Name: Membrane copper amine oxidase (AOC3)
• Synonyms: Vascular adhesion protein-1; Vascular adhesion protein 1; VAP1; VAP-1; Semicarbazide-sensitive amine oxidase; SSAO; Membrane primary amine oxidase; HPAO; Copper amine oxidase
• Gene Name: AOC3
• DTT Type: Successful target; [1]
• Related Disease: Hypertension [ICD-11: BA00-BA04]
• BioChemical Class: CH-NH(2) donor oxidoreductase
• UniProt ID: AOC3_HUMAN
• TTD ID: T69619
• EC Number: EC 1.4.3.21
• Sequence:
  MNQKTILVLLILAVITIFALVCVLLVGRGGDGGEPSQLPHCPSVSPSAQPWTHPGQSQLF
  ADLSREELTAVMRFLTQRLGPGLVDAAQARPSDNCVFSVELQLPPKAAALAHLDRGSPPP
  AREALAIVFFGRQPQPNVSELVVGPLPHPSYMRDVTVERHGGPLPYHRRPVLFQEYLDID
  QMIFNRELPQASGLLHHCCFYKHRGRNLVTMTTAPRGLQSGDRATWFGLYYNISGAGFFL
  HHVGLELLVNHKALDPARWTIQKVFYQGRYYDSLAQLEAQFEAGLVNVVLIPDNGTGGSW
  SLKSPVPPGPAPPLQFYPQGPRFSVQGSRVASSLWTFSFGLGAFSGPRIFDVRFQGERLV
  YEISLQEALAIYGGNSPAAMTTRYVDGGFGMGKYTTPLTRGVDCPYLATYVDWHFLLESQ
  APKTIRDAFCVFEQNQGLPLRRHHSDLYSHYFGGLAETVLVVRSMSTLLNYDYVWDTVFH
  PSGAIEIRFYATGYISSAFLFGATGKYGNQVSEHTLGTVHTHSAHFKVDLDVAGLENWVW
  AEDMVFVPMAVPWSPEHQLQRLQVTRKLLEMEEQAAFLVGSATPRYLYLASNHSNKWGHP
  RGYRIQMLSFAGEPLPQNSSMARGFSWERYQLAVTQRKEEEPSSSSVFNQNDPWAPTVDF
  SDFINNETIAGKDLVAWVTAGFLHIPHAEDIPNTVTVGNGVGFFLRPYNFFDEDPSFYSA
  DSIYFRGDQDAGACEVNPLACLPQAAACAPDLPAFSHGGFSHN
• Function: Has semicarbazide-sensitive (SSAO) monoamine oxidase activity. May play a role in adipogenesis. Cell adhesion protein that participates in lymphocyte extravasation and recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin-independent fashion.
• KEGG Pathway:
  Glycine, serine and threonine metabolism (hsa00260)
  Tyrosine metabolism (hsa00350)
  Phenylalanine metabolism (hsa00360)
  beta-Alanine metabolism (hsa00410)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Phase I - Functionalization of compounds (R-HSA-211945)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clonidine	DM6RZ9Q	Hypertension	BA00-BA04	Approved	[1]
Hydralazine	DMU8JGH	Hypertension	BA00-BA04	Approved	[2]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ASP8232	DMYK1JU	Diabetic macular edema	9B71.02	Phase 2	[3]
BTT-1023	DMIEPJG	Psoriasis vulgaris	EA90	Phase 2	[4]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BI 1467335	DMTE3UV	Diabetic retinopathy	9B71.0	Discontinued in Phase 2	[5]
Vapaliximab	DM73EPK	Inflammation	1A00-CA43.1	Terminated	[6]

7 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
6-hydroxydopa quinone	DM7M58P	Discovery agent	N.A.	Investigative	[7]
FP-1102	DMGID4T	Vascular disease	BE2Z	Investigative	[8]
LJP-1207	DMJ108U	Cerebrovascular ischaemia	8B1Z	Investigative	[8]
PSX-4206	DMVJDCM	Pulmonary disease	1B10-1F85	Investigative	[8]
PXS-4159	DMHCEOU	Asthma	CA23	Investigative	[8]
RTU-1096	DMWVBD9	Atopic dermatitis	EA80	Investigative	[8]
Vapill	DM30E56	Diabetic complication	5A2Y	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Psoriasis	EA90	Skin	8.36E-22	-1.03	-1.54
Asthma	CA23	Nasal and bronchial airway	7.20E-02	-0.07	-0.06
Atopic dermatitis	EA90	Skin	6.72E-01	-0.02	-0.03

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

• DTT DME Name: Copper amine oxidase (AOC3) DME Info
• Gene Name: AOC3

1 Discontinued Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tresperimus	DMOVBSF	Autoimmune diabetes	5A10	Discontinued in Phase 3	[9]

4 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Benzylamine	DMRM6ES	Chronic functional vomiting	DD90.4	Investigative	[10]
Methylamine	DMTPL4W	Discovery agent	N.A.	Investigative	[10]
Phenethylamine	DMX0G4F	Discovery agent	N.A.	Investigative	[10]
Tyramine	DM4UXT1	Discovery agent	N.A.	Investigative	[10]

References

• [1] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Preclinical evaluation of a radioiodinated fully human antibody for in vivo imaging of vascular adhesion protein-1-positive vasculature in inflammation. J Nucl Med. 2013 Aug;54(8):1315-9.
• [5] Clinical pipeline report, company report or official report of Boehringer Ingelheim.
• [6] Clinical pipeline report, company report or official report of Huginonline.
• [7] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [8] 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: 2767).
• [9] Metabolism of tresperimus by rat aorta semicarbazide-sensitive amine oxidase (SSAO). Fundam Clin Pharmacol. 2002 Dec;16(6):461-70.
• [10] The unique substrate specificity of human AOC2, a semicarbazide-sensitive amine oxidase. Cell Mol Life Sci. 2009 Aug;66(16):2743-57.