Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTD7Q0R)

• DTT Name: Cytochrome P450 26 (CYP26A1)
• Synonyms: Retinoic acid-metabolizing cytochrome; Retinoic acid inducible enzyme; Retinoic acid 4-hydroxylase; P450RAI; P450 retinoic acid-inactivating 1; HP450RAI; Cytochrome P450RAI; CYP26A1
• Gene Name: CYP26A1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Paired donor oxygen oxidoreductase
• UniProt ID: CP26A_HUMAN
• TTD ID: T84634
• EC Number: EC 1.14.13.-
• Sequence:
  MGLPALLASALCTFVLPLLLFLAAIKLWDLYCVSGRDRSCALPLPPGTMGFPFFGETLQM
  VLQRRKFLQMKRRKYGFIYKTHLFGRPTVRVMGADNVRRILLGEHRLVSVHWPASVRTIL
  GSGCLSNLHDSSHKQRKKVIMRAFSREALECYVPVITEEVGSSLEQWLSCGERGLLVYPE
  VKRLMFRIAMRILLGCEPQLAGDGDSEQQLVEAFEEMTRNLFSLPIDVPFSGLYRGMKAR
  NLIHARIEQNIRAKICGLRASEAGQGCKDALQLLIEHSWERGERLDMQALKQSSTELLFG
  GHETTASAATSLITYLGLYPHVLQKVREELKSKGLLCKSNQDNKLDMEILEQLKYIGCVI
  KETLRLNPPVPGGFRVALKTFELNGYQIPKGWNVIYSICDTHDVAEIFTNKEEFNPDRFM
  LPHPEDASRFSFIPFGGGLRSCVGKEFAKILLKIFTVELARHCDWQLLNGPPTMKTSPTV
  YPVDNLPARFTHFHGEI
• Function: Plays a key role in retinoic acid metabolism. Acts on retinoids, including all-trans-retinoic acid (RA) and its stereoisomer 9-cis-RA. Capable of both 4-hydroxylation and 18- hydroxylation. Responsible for generation of several hydroxylated forms of RA, including 4-OH-RA, 4-oxo-RA and 18-OH-RA.
• 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 DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LIAROZOLE	DM4OYXE	Dermatological disease	DA24.Y	Phase 2/3	[1]
Rambazole	DMP2DNS	Psoriasis vulgaris	EA90	Phase 2	[2]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-((+/-)-(1H-imidazol-1-yl)-(E)-methylretinoate	DMI15VQ	Discovery agent	N.A.	Investigative	[3]
4-((+/-)-(1H-imidazol-1-yl)-(E)-retinoic acid	DMKYB4D	Discovery agent	N.A.	Investigative	[3]

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

• DTT DME Name: Retinoic acid 4-hydroxylase 26A1 (CYP26A1) DME Info
• Gene Name: CYP26A1

1 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vitamin A	DMJ2AH4	Night blindness	9D45	Approved	[4]

References

• [1] Novel azolyl-(phenylmethyl)]aryl/heteroarylamines: potent CYP26 inhibitors and enhancers of all-trans retinoic acid activity in neuroblastoma cells. Bioorg Med Chem. 2008 Sep 1;16(17):8301-13.
• [2] Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
• [3] Novel retinoic acid metabolism blocking agents endowed with multiple biological activities are efficient growth inhibitors of human breast and pros... J Med Chem. 2004 Dec 30;47(27):6716-29.
• [4] Induction of CYP26A1 by metabolites of retinoic acid: evidence that CYP26A1 is an important enzyme in the elimination of active retinoids. Mol Pharmacol. 2015;87(3):430-41.