Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT11E62Y)

• DOT Name: Spermine oxidase (SMOX)
• Synonyms: EC 1.5.3.16; Polyamine oxidase 1; PAO-1; PAOh1
• Gene Name: SMOX
• UniProt ID: SMOX_HUMAN
• PDB ID: 7OXL; 7OY0
• EC Number: 1.5.3.16
• Pfam ID: PF01593
• Sequence:
  MQSCESSGDSADDPLSRGLRRRGQPRVVVIGAGLAGLAAAKALLEQGFTDVTVLEASSHI
  GGRVQSVKLGHATFELGATWIHGSHGNPIYHLAEANGLLEETTDGERSVGRISLYSKNGV
  ACYLTNHGRRIPKDVVEEFSDLYNEVYNLTQEFFRHDKPVNAESQNSVGVFTREEVRNRI
  RNDPDDPEATKRLKLAMIQQYLKVESCESSSHSMDEVSLSAFGEWTEIPGAHHIIPSGFM
  RVVELLAEGIPAHVIQLGKPVRCIHWDQASARPRGPEIEPRGEGDHNHDTGEGGQGGEEP
  RGGRWDEDEQWSVVVECEDCELIPADHVIVTVSLGVLKRQYTSFFRPGLPTEKVAAIHRL
  GIGTTDKIFLEFEEPFWGPECNSLQFVWEDEAESHTLTYPPELWYRKICGFDVLYPPERY
  GHVLSGWICGEEALVMEKCDDEAVAEICTEMLRQFTGNPNIPKPRRILRSAWGSNPYFRG
  SYSYTQVGSSGADVEKLAKPLPYTESSKTAPMQVLFSGEATHRKYYSTTHGALLSGQREA
  ARLIEMYRDLFQQGT
• Function: Flavoenzyme which catalyzes the oxidation of spermine to spermidine. Can also use N(1)-acetylspermine and spermidine as substrates, with different affinity depending on the isoform (isozyme) and on the experimental conditions. Plays an important role in the regulation of polyamine intracellular concentration and has the potential to act as a determinant of cellular sensitivity to the antitumor polyamine analogs. May contribute to beta-alanine production via aldehyde dehydrogenase conversion of 3-amino-propanal.
• Tissue Specificity: Widely expressed. Expressed in human tumor cell lines. Isoform 4 is only found in an embryonal kidney cell line.
• KEGG Pathway:
  Arginine and proline metabolism (hsa00330)
  beta-Alanine metabolism (hsa00410)
  Metabolic pathways (hsa01100)
• BioCyc Pathway: MetaCyc:HS01609-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Spermine	DMD4BFY	Terminated	Spermine oxidase (SMOX) increases the oxidation of Spermine.	[29]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Spermine oxidase (SMOX).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Spermine oxidase (SMOX).	[22]

36 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Spermine oxidase (SMOX).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Spermine oxidase (SMOX).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Spermine oxidase (SMOX).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Spermine oxidase (SMOX).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Spermine oxidase (SMOX).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Spermine oxidase (SMOX).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Spermine oxidase (SMOX).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Spermine oxidase (SMOX).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Spermine oxidase (SMOX).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Spermine oxidase (SMOX).	[11]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Spermine oxidase (SMOX).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Spermine oxidase (SMOX).	[12]
Selenium	DM25CGV	Approved	Selenium increases the expression of Spermine oxidase (SMOX).	[13]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Spermine oxidase (SMOX).	[14]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Spermine oxidase (SMOX).	[15]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Spermine oxidase (SMOX).	[16]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Spermine oxidase (SMOX).	[17]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Spermine oxidase (SMOX).	[18]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Spermine oxidase (SMOX).	[16]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Spermine oxidase (SMOX).	[19]
Estrone	DM5T6US	Approved	Estrone increases the expression of Spermine oxidase (SMOX).	[16]
Mestranol	DMG3F94	Approved	Mestranol increases the expression of Spermine oxidase (SMOX).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Spermine oxidase (SMOX).	[20]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Spermine oxidase (SMOX).	[3]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Spermine oxidase (SMOX).	[8]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Spermine oxidase (SMOX).	[21]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Spermine oxidase (SMOX).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Spermine oxidase (SMOX).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Spermine oxidase (SMOX).	[24]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Spermine oxidase (SMOX).	[4]
HEXESTROL	DM9AGWQ	Withdrawn from market	HEXESTROL increases the expression of Spermine oxidase (SMOX).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Spermine oxidase (SMOX).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Spermine oxidase (SMOX).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Spermine oxidase (SMOX).	[27]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Spermine oxidase (SMOX).	[28]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Spermine oxidase (SMOX).	[29]

References

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