Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTILF8T)

• DOT Name: Flavin-containing monooxygenase 5 (FMO5)
• Synonyms: FMO 5; Baeyer-Villiger monooxygenase 1; hBVMO1; EC 1.14.13.-; Dimethylaniline monooxygenase 5; EC 1.14.13.8; Dimethylaniline oxidase 5; NADPH oxidase; EC 1.6.3.1
• Gene Name: FMO5
• Related Disease: Congenital heart disease
• UniProt ID: FMO5_HUMAN
• EC Number: 1.14.13.-; 1.14.13.8; 1.6.3.1
• Pfam ID: PF00743
• Sequence:
  MTKKRIAVIGGGVSGLSSIKCCVEEGLEPVCFERTDDIGGLWRFQENPEEGRASIYKSVI
  INTSKEMMCFSDYPIPDHYPNFMHNAQVLEYFRMYAKEFDLLKYIRFKTTVCSVKKQPDF
  ATSGQWEVVTESEGKKEMNVFDGVMVCTGHHTNAHLPLESFPGIEKFKGQYFHSRDYKNP
  EGFTGKRVIIIGIGNSGGDLAVEISQTAKQVFLSTRRGAWILNRVGDYGYPADVLFSSRL
  THFIWKICGQSLANKYLEKKINQRFDHEMFGLKPKHRALSQHPTLNDDLPNRIISGLVKV
  KGNVKEFTETAAIFEDGSREDDIDAVIFATGYSFDFPFLEDSVKVVKNKISLYKKVFPPN
  LERPTLAIIGLIQPLGAIMPISELQGRWATQVFKGLKTLPSQSEMMAEISKAQEEIDKRY
  VESQRHTIQGDYIDTMEELADLVGVRPNLLSLAFTDPKLALHLLLGPCTPIHYRVQGPGK
  WDGARKAILTTDDRIRKPLMTRVVERSSSMTSTMTIGKFMLALAFFAIIIAYF
• Function: Acts as a Baeyer-Villiger monooxygenase on a broad range of substrates. Catalyzes the insertion of an oxygen atom into a carbon-carbon bond adjacent to a carbonyl, which converts ketones to esters. Active on diverse carbonyl compounds, whereas soft nucleophiles are mostly non- or poorly reactive. In contrast with other forms of FMO it is non- or poorly active on 'classical' substrates such as drugs, pesticides, and dietary components containing soft nucleophilic heteroatoms (Probable). Able to oxidize drug molecules bearing a carbonyl group on an aliphatic chain, such as nabumetone and pentoxifylline. Also, in the absence of substrates, shows slow but yet significant NADPH oxidase activity. Acts as a positive modulator of cholesterol biosynthesis as well as glucose homeostasis, promoting metabolic aging via pleiotropic effects.
• Tissue Specificity: Expressed in fetal and adult liver.
• KEGG Pathway:
  Taurine and hypotaurine metabolism (hsa00430)
  Drug metabolism - cytochrome P450 (hsa00982)
  Metabolic pathways (hsa01100)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital heart disease	DISQBA23	Disputed	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Flavin-containing monooxygenase 5 (FMO5).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Flavin-containing monooxygenase 5 (FMO5).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Flavin-containing monooxygenase 5 (FMO5).	[8]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[9]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[10]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[11]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[10]
Penicillamine	DM40EF6	Approved	Penicillamine increases the expression of Flavin-containing monooxygenase 5 (FMO5).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[13]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Flavin-containing monooxygenase 5 (FMO5).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[15]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[16]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Flavin-containing monooxygenase 5 (FMO5).	[17]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Flavin-containing monooxygenase 5 (FMO5).	[18]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Flavin-containing monooxygenase 5 (FMO5).	[19]

References

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• [14] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
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• [16] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [17] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [18] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [19] The cinnamon-derived Michael acceptor cinnamic aldehyde impairs melanoma cell proliferation, invasiveness, and tumor growth. Free Radic Biol Med. 2009 Jan 15;46(2):220-31.