Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL1DFWV)

• DOT Name: Cytochrome P450 26A1 (CYP26A1)
• Synonyms: CYP26A1; EC 1.14.13.-; Cytochrome P450 retinoic acid-inactivating 1; Cytochrome P450RAI; hP450RAI; Retinoic acid 4-hydroxylase; Retinoic acid-metabolizing cytochrome
• Gene Name: CYP26A1
• UniProt ID: CP26A_HUMAN
• EC Number: 1.14.13.-
• Pfam ID: PF00067
• Sequence:
  MGLPALLASALCTFVLPLLLFLAAIKLWDLYCVSGRDRSCALPLPPGTMGFPFFGETLQM
  VLQRRKFLQMKRRKYGFIYKTHLFGRPTVRVMGADNVRRILLGEHRLVSVHWPASVRTIL
  GSGCLSNLHDSSHKQRKKVIMRAFSREALECYVPVITEEVGSSLEQWLSCGERGLLVYPE
  VKRLMFRIAMRILLGCEPQLAGDGDSEQQLVEAFEEMTRNLFSLPIDVPFSGLYRGMKAR
  NLIHARIEQNIRAKICGLRASEAGQGCKDALQLLIEHSWERGERLDMQALKQSSTELLFG
  GHETTASAATSLITYLGLYPHVLQKVREELKSKGLLCKSNQDNKLDMEILEQLKYIGCVI
  KETLRLNPPVPGGFRVALKTFELNGYQIPKGWNVIYSICDTHDVAEIFTNKEEFNPDRFM
  LPHPEDASRFSFIPFGGGLRSCVGKEFAKILLKIFTVELARHCDWQLLNGPPTMKTSPTV
  YPVDNLPARFTHFHGEI
• Function: A cytochrome P450 monooxygenase involved in the metabolism of retinoates (RAs), the active metabolites of vitamin A, and critical signaling molecules in animals. RAs exist as at least four different isomers: all-trans-RA (atRA), 9-cis-RA, 13-cis-RA, and 9,13-dicis-RA, where atRA is considered to be the biologically active isomer, although 9-cis-RA and 13-cis-RA also have activity (Probable). Catalyzes the hydroxylation of atRA primarily at C-4 and C-18, thereby contributing to the regulation of atRA homeostasis and signaling. Hydroxylation of atRA limits its biological activity and initiates a degradative process leading to its eventual elimination (Probable). Involved in the convertion of atRA to all-trans-4-oxo-RA. Able to metabolize other RAs such as 9-cis, 13-cis and 9,13-di-cis RA. Can oxidize all-trans-13,14-dihydroretinoate (DRA) to metabolites which could include all-trans-4-oxo-DRA, all-trans-4-hydroxy-DRA, all-trans-5,8-epoxy-DRA, and all-trans-18-hydroxy-DRA. May play a role in the oxidative metabolism of xenobiotics such as tazarotenic acid.
• Tissue Specificity: Expressed in most fetal and adult tissues with highest levels in adult liver, heart, pituitary gland, adrenal gland, placenta and regions of the brain . Expressed at high levels in lung, pancreas, skin and uterus (at protein level) . Lower expression level is detected in spleen, kidney, intestine and adipose tissue (at protein level) .
• KEGG Pathway:
  Retinol metabolism (hsa00830)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  RA biosynthesis pathway (R-HSA-5365859)
  Vitamins (R-HSA-211916)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Cytochrome P450 26A1 (CYP26A1) decreases the metabolism of Tretinoin.	[29]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cytochrome P450 26A1 (CYP26A1) decreases the response to substance of Cisplatin.	[30]
Hydrogen peroxide	DM1NG5W	Approved	Cytochrome P450 26A1 (CYP26A1) decreases the response to substance of Hydrogen peroxide.	[30]
Etoposide	DMNH3PG	Approved	Cytochrome P450 26A1 (CYP26A1) decreases the response to substance of Etoposide.	[30]

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 Cytochrome P450 26A1 (CYP26A1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Cytochrome P450 26A1 (CYP26A1).	[20]

32 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 Cytochrome P450 26A1 (CYP26A1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytochrome P450 26A1 (CYP26A1).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cytochrome P450 26A1 (CYP26A1).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cytochrome P450 26A1 (CYP26A1).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cytochrome P450 26A1 (CYP26A1).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Cytochrome P450 26A1 (CYP26A1).	[7]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Cytochrome P450 26A1 (CYP26A1).	[8]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Cytochrome P450 26A1 (CYP26A1).	[9]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Cytochrome P450 26A1 (CYP26A1).	[10]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Cytochrome P450 26A1 (CYP26A1).	[11]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Cytochrome P450 26A1 (CYP26A1).	[9]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Cytochrome P450 26A1 (CYP26A1).	[12]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Cytochrome P450 26A1 (CYP26A1).	[13]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Cytochrome P450 26A1 (CYP26A1).	[9]
Dolutegravir	DMCZGRE	Approved	Dolutegravir decreases the expression of Cytochrome P450 26A1 (CYP26A1).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cytochrome P450 26A1 (CYP26A1).	[15]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Cytochrome P450 26A1 (CYP26A1).	[16]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Cytochrome P450 26A1 (CYP26A1).	[17]
LIAROZOLE	DM4OYXE	Phase 2/3	LIAROZOLE decreases the activity of Cytochrome P450 26A1 (CYP26A1).	[18]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Cytochrome P450 26A1 (CYP26A1).	[15]
Rambazole	DMP2DNS	Phase 2	Rambazole decreases the activity of Cytochrome P450 26A1 (CYP26A1).	[19]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Cytochrome P450 26A1 (CYP26A1).	[21]
MG-132	DMKA2YS	Preclinical	MG-132 decreases the expression of Cytochrome P450 26A1 (CYP26A1).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cytochrome P450 26A1 (CYP26A1).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cytochrome P450 26A1 (CYP26A1).	[24]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Cytochrome P450 26A1 (CYP26A1).	[25]
AHPN	DM8G6O4	Investigative	AHPN increases the expression of Cytochrome P450 26A1 (CYP26A1).	[21]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Cytochrome P450 26A1 (CYP26A1).	[19]
	DM9CEI5		increases the expression of Cytochrome P450 26A1 (CYP26A1).	[26]
All-trans-retinal	DM6CEVB	Investigative	All-trans-retinal increases the expression of Cytochrome P450 26A1 (CYP26A1).	[27]
TTNPB	DMSABD0	Investigative	TTNPB increases the expression of Cytochrome P450 26A1 (CYP26A1).	[28]
chlordane	DMMHU8G	Investigative	chlordane increases the expression of Cytochrome P450 26A1 (CYP26A1).	[28]

References

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