Target Information
| Target General Information | Top | |||||
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| Target ID |
T84634
(Former ID: TTDC00232)
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| Target Name |
Cytochrome P450 26 (CYP26A1)
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| Synonyms |
Retinoic acid-metabolizing cytochrome; Retinoic acid inducible enzyme; Retinoic acid 4-hydroxylase; P450RAI; P450 retinoic acid-inactivating 1; HP450RAI; Cytochrome P450RAI; CYP26A1
Click to Show/Hide
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| Gene Name |
CYP26A1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Oesophagitis [ICD-11: DA24] | |||||
| 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.
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| BioChemical Class |
Paired donor oxygen oxidoreductase
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| UniProt ID | ||||||
| EC Number |
EC 1.14.13.-
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| Sequence |
MGLPALLASALCTFVLPLLLFLAAIKLWDLYCVSGRDRSCALPLPPGTMGFPFFGETLQM
VLQRRKFLQMKRRKYGFIYKTHLFGRPTVRVMGADNVRRILLGEHRLVSVHWPASVRTIL GSGCLSNLHDSSHKQRKKVIMRAFSREALECYVPVITEEVGSSLEQWLSCGERGLLVYPE VKRLMFRIAMRILLGCEPQLAGDGDSEQQLVEAFEEMTRNLFSLPIDVPFSGLYRGMKAR NLIHARIEQNIRAKICGLRASEAGQGCKDALQLLIEHSWERGERLDMQALKQSSTELLFG GHETTASAATSLITYLGLYPHVLQKVREELKSKGLLCKSNQDNKLDMEILEQLKYIGCVI KETLRLNPPVPGGFRVALKTFELNGYQIPKGWNVIYSICDTHDVAEIFTNKEEFNPDRFM LPHPEDASRFSFIPFGGGLRSCVGKEFAKILLKIFTVELARHCDWQLLNGPPTMKTSPTV YPVDNLPARFTHFHGEI Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T55H1Y | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | LIAROZOLE | Drug Info | Phase 2/3 | Dermatological disease | [2], [3] | |
| 2 | Rambazole | Drug Info | Phase 2 | Psoriasis vulgaris | [4] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 4 Inhibitor drugs | + | ||||
| 1 | LIAROZOLE | Drug Info | [1] | |||
| 2 | Rambazole | Drug Info | [4] | |||
| 3 | 4-((+/-)-(1H-imidazol-1-yl)-(E)-methylretinoate | Drug Info | [5] | |||
| 4 | 4-((+/-)-(1H-imidazol-1-yl)-(E)-retinoic acid | Drug Info | [5] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Retinol metabolism | hsa00830 | Affiliated Target |
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| Class: Metabolism => Metabolism of cofactors and vitamins | Pathway Hierarchy | ||
| Degree | 9 | Degree centrality | 9.67E-04 | Betweenness centrality | 3.51E-03 |
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| Closeness centrality | 1.70E-01 | Radiality | 1.27E+01 | Clustering coefficient | 8.33E-02 |
| Neighborhood connectivity | 5.44E+00 | Topological coefficient | 1.92E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Retinol metabolism | |||||
| 2 | Metabolic pathways | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Retinol Metabolism | |||||
| WikiPathways | [+] 6 WikiPathways | + | ||||
| 1 | Vitamin A and Carotenoid Metabolism | |||||
| 2 | Metapathway biotransformation | |||||
| 3 | Oxidation by Cytochrome P450 | |||||
| 4 | Nuclear Receptors in Lipid Metabolism and Toxicity | |||||
| 5 | Adipogenesis | |||||
| 6 | Phase 1 - Functionalization of compounds | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 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. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5210). | |||||
| REF 3 | ClinicalTrials.gov (NCT00282724) Efficacy and Safety of Two Doses of Liarozole vs. Placebo for the Treatment of Lamellar Ichthyosis. U.S. National Institutes of Health. | |||||
| REF 4 | Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63. | |||||
| REF 5 | 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. | |||||
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