Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT3MOS2)

• DTT Name: Aldehyde oxidase (AOX1)
• Synonyms: AOX1
• Gene Name: AOX1
• DTT Type: Successful target; [1]
• BioChemical Class: Aldehyde/oxo donor oxidoreductase
• UniProt ID: AOXA_HUMAN
• TTD ID: T94444
• EC Number: EC 1.2.3.1
• Sequence:
  MDRASELLFYVNGRKVIEKNVDPETMLLPYLRKKLRLTGTKYGCGGGGCGACTVMISRYN
  PITKRIRHHPANACLIPICSLYGAAVTTVEGIGSTHTRIHPVQERIAKCHGTQCGFCTPG
  MVMSIYTLLRNHPEPTLDQLTDALGGNLCRCTGYRPIIDACKTFCKTSGCCQSKENGVCC
  LDQGINGLPEFEEGSKTSPKLFAEEEFLPLDPTQELIFPPELMIMAEKQSQRTRVFGSER
  MMWFSPVTLKELLEFKFKYPQAPVIMGNTSVGPEVKFKGVFHPVIISPDRIEELSVVNHA
  YNGLTLGAGLSLAQVKDILADVVQKLPEEKTQMYHALLKHLGTLAGSQIRNMASLGGHII
  SRHPDSDLNPILAVGNCTLNLLSKEGKRQIPLNEQFLSKCPNADLKPQEILVSVNIPYSR
  KWEFVSAFRQAQRQENALAIVNSGMRVFFGEGDGIIRELCISYGGVGPATICAKNSCQKL
  IGRHWNEQMLDIACRLILNEVSLLGSAPGGKVEFKRTLIISFLFKFYLEVSQILKKMDPV
  HYPSLADKYESALEDLHSKHHCSTLKYQNIGPKQHPEDPIGHPIMHLSGVKHATGEAIYC
  DDMPLVDQELFLTFVTSSRAHAKIVSIDLSEALSMPGVVDIMTAEHLSDVNSFCFFTEAE
  KFLATDKVFCVGQLVCAVLADSEVQAKRAAKRVKIVYQDLEPLILTIEESIQHNSSFKPE
  RKLEYGNVDEAFKVVDQILEGEIHMGGQEHFYMETQSMLVVPKGEDQEMDVYVSTQFPKY
  IQDIVASTLKLPANKVMCHVRRVGGAFGGKVLKTGIIAAVTAFAANKHGRAVRCVLERGE
  DMLITGGRHPYLGKYKAGFMNDGRILALDMEHYSNAGASLDESLFVIEMGLLKMDNAYKF
  PNLRCRGWACRTNLPSNTAFRGFGFPQAALITESCITEVAAKCGLSPEKVRIINMYKEID
  QTPYKQEINAKNLIQCWRECMAMSSYSLRKVAVEKFNAENYWKKKGLAMVPLKFPVGLGS
  RAAGQAAALVHIYLDGSVLVTHGGIEMGQGVHTKMIQVVSRELRMPMSNVHLRGTSTETV
  PNANISGGSVVADLNGLAVKDACQTLLKRLEPIISKNPKGTWKDWAQTAFDESINLSAVG
  YFRGYESDMNWEKGEGQPFEYFVYGAACSEVEIDCLTGDHKNIRTDIVMDVGCSINPAID
  IGQIEGAFIQGMGLYTIEELNYSPQGILHTRGPDQYKIPAICDMPTELHIALLPPSQNSN
  TLYSSKGLGESGVFLGCSVFFAIHDAVSAARQERGLHGPLTLNSPLTPEKIRMACEDKFT
  KMIPRDEPGSYVPWNVPI
• Function: Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N- methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir topenciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. Also may catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis.
• KEGG Pathway:
  Valine, leucine and isoleucine degradation (hsa00280)
  Tyrosine metabolism (hsa00350)
  Tryptophan metabolism (hsa00380)
  Vitamin B6 metabolism (hsa00750)
  Nicotinate and nicotinamide metabolism (hsa00760)
  Retinol metabolism (hsa00830)
  Drug metabolism - cytochrome P450 (hsa00982)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Vitamins B6 activation to pyridoxal phosphate (R-HSA-964975)
• BioCyc Pathway: MetaCyc:ENSG00000138356-MON

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Isovanillin	DMX7LKS	Solid tumour/cancer	2A00-2F9Z	Approved	[2]
Menadione	DMSJDTY	Vitamin K deficiency	5B59	Approved	[1]

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

• DTT DME Name: Aldehyde oxidase (AOX1) DME Info
• Gene Name: AOX1

2 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zaleplon	DMGFWSM	Insomnia	7A00-7A0Z	Approved	[3]
Ziprasidone	DMM58JY	Bipolar disorder	6A60	Approved	[]

2 Clinical Trial Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
XL147	DMML7BE	Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
SGX523	DM3RSMF	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]

1 Preclinical Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VUFB-11502	DM7WFR0	N. A.	N. A.	Preclinical	[5]

References

• [1] Inhibition by SKF-525A of the aldehyde oxidase-mediated metabolism of the experimental antitumour agent acridine carboxamide. Biochem Pharmacol. 1993 May 25;45(10):2159-62.
• [2] Contribution of aldehyde oxidizing enzymes on the metabolism of 3,4-dimethoxy-2-phenylethylamine to 3,4-dimethoxyphenylacetic acid by guinea pig li... Cell Physiol Biochem. 2006;17(1-2):47-56.
• [3] Characterization of aldehyde oxidase enzyme activity in cryopreserved human hepatocytes. Drug Metab Dispos. 2012 Feb;40(2):267-75.
• [4] Species-specific metabolism of SGX523 by aldehyde oxidase and the toxicological implications. Drug Metab Dispos. 2010 Aug;38(8):1277-85.
• [5] The critical role of oxidative stress in the toxicity and metabolism of quinoxaline 1,4-di-N-oxides in vitro and in vivo. Drug Metab Rev. 2016 May;48(2):159-82.