CYP26A1

Summary

CYP26A1 (cytochrome P450 family 26 subfamily A member 1, HGNC:2603) is a protein-coding gene on chromosome 10q23.33, encoding Cytochrome P450 26A1 (O43174). A cytochrome P450 monooxygenase involved in the metabolism of retinoates (RAs), the active metabolites of vitamin A, and critical signaling molecules in animals.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum protein acts on retinoids, including all-trans-retinoic acid (RA), with both 4-hydroxylation and 18-hydroxylation activities. This enzyme regulates the cellular level of retinoic acid which is involved in regulation of gene expression in both embryonic and adult tissues. Two alternatively spliced transcript variants of this gene, which encode the distinct isoforms, have been reported.

Source: NCBI Gene 1592 — RefSeq curated summary.

At a glance

• GWAS associations: 68
• Clinical variants (ClinVar): 71 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000783

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2603
Approved symbol	CYP26A1
Name	cytochrome P450 family 26 subfamily A member 1
Location	10q23.33
Locus type	gene with protein product
Status	Approved
Aliases	P450RAI, CP26, CYP26, P450RAI1
Ensembl gene	ENSG00000095596
Ensembl biotype	protein_coding
OMIM	602239
Entrez	1592

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 retained_intron, 2 protein_coding, 1 nonsense_mediated_decay

ENST00000224356, ENST00000371531, ENST00000622925, ENST00000623162, ENST00000624589, ENST00000625202

RefSeq mRNA: 2 — MANE Select: NM_000783 NM_000783, NM_057157

CCDS: CCDS7426, CCDS7427

Canonical transcript exons

ENST00000224356 — 7 exons

Exon	Start	End
ENSE00000613213	93076544	93076696
ENSE00000714715	93075149	93075307
ENSE00000986564	93074779	93075069
ENSE00000986565	93075826	93075960
ENSE00001402485	93076963	93077885
ENSE00003525350	93074308	93074532
ENSE00003538418	93073893	93074123

Expression profiles

Bgee: expression breadth broad, 97 present calls, max score 84.77.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5567 / max 135.6286, expressed in 222 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106271	1.2658	204
106270	0.1763	66
106272	0.1146	60

Top tissues by expression

114 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	84.77	gold quality
right lobe of liver	UBERON:0001114	84.52	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.07	gold quality
liver	UBERON:0002107	81.35	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.28	silver quality
placenta	UBERON:0001987	70.49	gold quality
endometrium	UBERON:0001295	69.18	gold quality
prefrontal cortex	UBERON:0000451	69.06	gold quality
superior frontal gyrus	UBERON:0002661	64.53	gold quality
frontal cortex	UBERON:0001870	64.13	gold quality
Brodmann (1909) area 9	UBERON:0013540	62.09	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	60.31	gold quality
cerebral cortex	UBERON:0000956	60.00	gold quality
anterior cingulate cortex	UBERON:0009835	59.09	gold quality
right frontal lobe	UBERON:0002810	56.49	gold quality
primary visual cortex	UBERON:0002436	55.41	gold quality
bone marrow cell	CL:0002092	54.07	silver quality
embryo	UBERON:0000922	53.41	gold quality
ganglionic eminence	UBERON:0004023	53.41	gold quality
granulocyte	CL:0000094	52.05	gold quality
mucosa of transverse colon	UBERON:0004991	51.03	gold quality
brain	UBERON:0000955	49.90	gold quality
Ammon’s horn	UBERON:0001954	48.73	gold quality
caudate nucleus	UBERON:0001873	48.55	gold quality
hypothalamus	UBERON:0001898	47.88	gold quality
adenohypophysis	UBERON:0002196	47.63	gold quality
thoracic mammary gland	UBERON:0005200	45.87	gold quality
putamen	UBERON:0001874	45.28	gold quality
ventricular zone	UBERON:0003053	44.43	gold quality
vermiform appendix	UBERON:0001154	44.24	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6524	yes	471.28
E-GEOD-81383	no	285.66
E-ANND-3	no	1.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, HESX1, HNF4A, NCOR1, RARA, RARB, RARG, RBPJ, RXRA, SP3, TCF7L2, THRA, ZIC1

miRNA regulators (miRDB)

36 targeting CYP26A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-4536-5P	98.47	64.39	657
HSA-MIR-943	97.81	64.42	694
HSA-MIR-483-3P	97.77	64.95	731
HSA-MIR-4724-3P	97.57	67.31	785
HSA-MIR-320E	97.49	65.96	865

Literature-anchored findings (GeneRIF, showing 34)

• increased CYP26-mediated catabolism of retinoic by CRABP-I transfection might decrease the amount of retinoic acid that is accessible to the nuclear receptors (PMID:15281009)
• The identification of a functional retinoic acid response element located 2.0 kb upstream of the Cyp26A1 transcriptional start site is reported. (PMID:16053444)
• induction and regulation of CYP26A1 expression in human intestinal (Caco-2), liver (HepG2), endothelial (HUVEC), and APL (NB4) cell lines (PMID:16194896)
• Variants in CYP26A1 are unlikely to be a major risk factor for caudal regression syndrome; further study with a larger number of genotyped subjects is required. (PMID:16463413)
• Constitutive expression of CYP26AI in vivo and in organotypic culture was found to be restricted to basal epidermal keratinocytes, as well as eccrine sweat glands and sebaceous glands. (PMID:16778795)
• g.3116delT mutation is of particular interest because it was identified in a patient with spina bifida and likely encodes a truncated protein with no enzymatic activity, as demonstrated by preliminary in vitro data. (PMID:16933217)
• analysis of CYP26A1 active site architecture and ligand binding (PMID:17059167)
• Low CYP26A1 expression may explain high risk of resistance installation, by increase retinoid pressure. (PMID:17218384)
• Three new alleles termed as CYP26A1*2, CYP26A1*3, and CYP26A1*4, are potentially defective in all-trans retinoic acid metabolism. (PMID:17460545)
• Overexpression of CYP26A1 causes intracellular retinoic acid depletion and drives the cell into a highly proliferative and invasive state with induction of other known oncogenes (PMID:18059332)
• Results provide a biochemical framework for CYP26A1 function and offer insight into the role of CYP26A1 as a drug target as well as in fetal development and cell cycle regulation (PMID:18992717)
• cytochrome P450 family 26 (CYP26) enzymes have a role in determining the cellular exposure to retinoic acid by inactivating retinoic acid in cells that do not need retinoic acid–REVIEW (PMID:19519282)
• CYP26A1 is expressed in human liver microsomes; its expression correlates with retinoic acid hydroxylation. (PMID:20513361)
• the functioning of multiple RAREs may account for the strong inducibility of CYP26A1 in liver, which, in turn, may be important physiologically for restoring retinoid homeostasis when the concentration of RA rises. (PMID:20682464)
• Primary metabolites of all-trans-retinoic acid formed by CYP26A1 are identified and the ligand selectivity and ligand interactions of CYP26A1 are characterized. (PMID:21521770)
• CYP26A1 and CYP26C1 play a pivotal role in the pathogenesis of nonsyndromic bilateral and unilateral optic nerve aplasia. (PMID:21850183)
• The promoter region of CYP26A1 is significantly hypermethylated in allergic asthmatic subjects. (PMID:21975512)
• CYP26A1 and CYP26B1 are qualitatively similar retinoic acid hydroxylases with overlapping expression profiles; CYP26A1 has higher catalytic activity than CYP26B1. (PMID:22020119)
• Our observation suggests an involvement of enhanced CYP26A1 expression causing a functional vitamin A deficieny state in skin that can potentially lead to neoplastic transformation of keratinocytes in an early phase during skin carcinogenesis (PMID:22179182)
• CYP26 is able to inactivate retinoids in serum, preventing retinoic acid signaling and thus bone-marrow hematopoietic stem cell differentiation. (PMID:24043786)
• HNF4alpha coordinates with retinoic acid receptors in a retinoic acid-dependent manner to strongly induce CYP26A1 gene expression in the liver, which may explain the high level of response to retinoic acid observed in vivo. (PMID:24819304)
• data suggested that CYP26A1 overexpression might contribute to the development and progression of cervical malignancies and squamous neoplasia of the head and neck (PMID:25294402)
• In liver microsomes, CYP26A1 plays a role in clearing bioactive retinoids. (PMID:25492813)
• Molecular recognition of CYP26A1 binding pockets and structure-activity relationship studies for design of potent and selective retinoic acid metabolism blocking agents has been described. (PMID:25541526)
• CYP26A1 polymorphisms were associated with increased risk of malignant oral disorders in betel quid chewers. (PMID:25839051)
• CYP26A1-mediated oncogenic characteristics may be partially responsible for the elevated expression of fascin. (PMID:26058854)
• Accumulating evidence suggest that cytochrome P450 (CYP26), the primary retinoid-inactivating enzyme, plays a critical role in the integration of two neoplastic molecular programs: the retinoid metabolism and Hedgehog pathways. (Review) (PMID:28754309)
• We applied whole-genome sequencing (WGS) on 9 trios where the probands are sporadically affected with the most severe form of the disorder and harbor no coding sequence variants affecting the function of known Hirschsprung disease (HSCR) genes. We found de novo protein-altering variants in three intolerant to change genes-CCT2, VASH1, and CYP26A1-for which a plausible link with the enteric nervous system (ENS) exists (PMID:29483666)
• Cytochrome P450 26A1 modulates uterine dendritic cells in mice early pregnancy. (PMID:31148354)
• This review highlights the current knowledge of structure-function of CYP26 enzymes and focuses on their role in human retinoid metabolism in different tissues. (PMID:31419517)
• The combined effects of the novel CYP26 single nucleotide polymorphisms -environment approach may predict the risk of occurrence of oral malignant disorders. (PMID:31465460)
• Identification of a novel CYP26A1 mutation in a Chinese family with congenital microtia. (PMID:33197841)
• A novel Cytochrome P450 26A1 expressing NK cell subset at the mouse maternal-foetal interface. (PMID:33438367)
• CYP26A1 Is a Novel Cancer Biomarker of Pancreatic Carcinoma: Evidence from Integration Analysis and In Vitro Experiments. (PMID:35707714)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyp26a1	ENSDARG00000033999
mus_musculus	Cyp26a1	ENSMUSG00000024987
rattus_norvegicus	Cyp26a1	ENSRNOG00000016750

Paralogs (2): CYP26B1 (ENSG00000003137), CYP26C1 (ENSG00000187553)

Protein

Protein identifiers

Cytochrome P450 26A1 — O43174 (reviewed: O43174)

Alternative names: Cytochrome P450 retinoic acid-inactivating 1, Retinoic acid 4-hydroxylase, Retinoic acid-metabolizing cytochrome

All UniProt accessions (2): O43174, A0A096LNN2

UniProt curated annotations — full annotation on UniProt →

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. 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. 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.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

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).

Induction. By retinoic acid.

Similarity. Belongs to the cytochrome P450 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43174-1	1	yes
O43174-2	2

RefSeq proteins (2): NP_000774, NP_476498 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002403	Cyt_P450_E_grp-IV	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily

Pfam: PF00067

Catalyzed reactions (Rhea), 3 shown:

• all-trans-retinoate + reduced [NADPH–hemoprotein reductase] + O2 = all-trans-(4S)-hydroxyretinoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:51492)
• all-trans-(4S)-hydroxyretinoate + reduced [NADPH–hemoprotein reductase] + O2 = all-trans-(4S,16)-dihydroxyretinoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:51632)
• all-trans-retinoate + reduced [NADPH–hemoprotein reductase] + O2 = all-trans-18-hydroxyretinoate + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:55856)

UniProt features (5 total): sequence conflict 2, chain 1, binding site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43174-F1	89.64	0.65

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 442 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-211916	Vitamins
R-HSA-5365859	RA biosynthesis pathway

MSigDB gene sets: 210 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, MODULE_93, REACTOME_BIOLOGICAL_OXIDATIONS, BENPORATH_ES_WITH_H3K27ME3, MYOGENIN_Q6, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GGGNRMNNYCAT_UNKNOWN, SHEPARD_CRASH_AND_BURN_MUTANT_UP, MODULE_45, GOBP_REGULATION_OF_RETINOIC_ACID_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, LEE_LIVER_CANCER_CIPROFIBRATE_DN, NFKB_Q6, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (10): kidney development (GO:0001822), vitamin metabolic process (GO:0006766), xenobiotic metabolic process (GO:0006805), central nervous system development (GO:0007417), response to retinoic acid (GO:0032526), response to vitamin A (GO:0033189), retinoic acid catabolic process (GO:0034653), retinoic acid metabolic process (GO:0042573), negative regulation of retinoic acid receptor signaling pathway (GO:0048387), lipid metabolic process (GO:0006629)

GO Molecular Function (12): retinoic acid binding (GO:0001972), monooxygenase activity (GO:0004497), iron ion binding (GO:0005506), retinoic acid 4-hydroxylase activity (GO:0008401), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen (GO:0016709), oxygen binding (GO:0019825), heme binding (GO:0020037), all-trans retinoic acid 4-hydrolase activity (GO:0062182), all-trans retinoic acid 18-hydroxylase activity (GO:0062183), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cytochrome P450 - arranged by substrate type	1
Signaling by Retinoic Acid	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monooxygenase activity	3
response to lipid	2
oxidoreductase activity	2
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	2
animal organ development	1
renal system development	1
small molecule metabolic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
nervous system development	1
system development	1
response to oxygen-containing compound	1
response to vitamin	1
diterpenoid catabolic process	1
fat-soluble vitamin catabolic process	1
retinoic acid metabolic process	1
monocarboxylic acid catabolic process	1
retinoid metabolic process	1
monocarboxylic acid metabolic process	1
hormone metabolic process	1
retinoic acid receptor signaling pathway	1
regulation of retinoic acid receptor signaling pathway	1
negative regulation of intracellular signal transduction	1
primary metabolic process	1
retinoid binding	1
monocarboxylic acid binding	1
transition metal ion binding	1
small molecule binding	1
tetrapyrrole binding	1
retinoic acid 4-hydroxylase activity	1
catalytic activity	1
cation binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2275 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP26A1	ALDH1A2	O94788	905
CYP26A1	RARS1	P54136	847
CYP26A1	RBP2	P50120	811
CYP26A1	STRA8	Q7Z7C7	797
CYP26A1	RDH10	Q8IZV5	749
CYP26A1	BFSP2	Q13515	741
CYP26A1	STRA6	Q9BX79	733
CYP26A1	RARB	P10826	731
CYP26A1	RARG	P13631	728
CYP26A1	RARA	P10276	726
CYP26A1	ALDH1A3	P47895	720
CYP26A1	LRAT	O95237	718
CYP26A1	RBP1	P09455	714
CYP26A1	CRABP2	P29373	709
CYP26A1	SCEL	O95171	693

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): CYP26A1 (Affinity Capture-MS), ILK (Positive Genetic), CYP26A1 (Affinity Capture-RNA), CYP26A1 (Affinity Capture-MS)

ESM2 similar proteins: A0A067DT54, A0A067E1K2, A0A0B4KZX8, A0A0B4L1W8, A0A0S2II38, A0A0U2U8U5, A0A140JWM8, A0A1I9Q5Z0, A0A3Q7HBJ5, A0A3Q7HS74, A0A517FNB9, A0A517FNC5, A0A517FNC6, A0A517FND3, A0A5A4DV62, A0A5B8ND22, A0A9Y1LLN2, A0AAW1JA93, A0AAW1NEA3, A5BFI4, A9QNE7, B5BSX1, B8AJL3, B8AV52, B9G934, F6H9N6, H2DH16, I1GQE7, I1H7R8, I7C6E8, I7CT85, K4CEE8, K7NBR2, O23051, O43174, O48786, O55127, O64989, O81077, O93323

Diamond homologs: A0A068A9T2, A0A068AA98, A0A068ACU3, A0A068Q609, A0A0P0ZEA9, A0A1B4XBH0, A0A1B4XBH8, A0A1L7VEQ6, A0A1L9WQK2, A0A1R3RGJ7, A0A1V1FNM9, A0A1Z3GBS4, A0A218NGS0, A0A2B7YFS5, A0A2H3CNS9, A0A2P1DPA5, A0A343URW6, A0A343URW7, A0A3Q9R4N5, A0A3S9NM20, A0A411KUQ5, A0A5B8NBK9, A0A6S6QP77, A0A831A9C9, A0A8K1AW54, A0A9E7S4M3, A1C8C2, A2R6G9, A2RRT9, A3A871, B4FVP3, B6HFX9, B8NM64, C8V7P3, D1MX85, G0KYB2, G1XU01, G3Y420, H2DH24, I7ZK32

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
“all-trans-retinoic acid”	“up-regulates activity”	CYP26A1	“chemical activation”
CYP26A1	“down-regulates quantity”	“all-trans-retinoic acid”	“chemical modification”
CYP26A1	“down-regulates activity”	“all-trans-retinoic acid”	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

71 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

772 predictions. Top by Δscore:

Variant	Effect	Δscore
10:93074121:CAG:C	donor_loss	1.0000
10:93074122:AGG:A	donor_loss	1.0000
10:93074123:GGTA:G	donor_loss	1.0000
10:93074124:G:GA	donor_loss	1.0000
10:93074292:C:CA	acceptor_gain	1.0000
10:93074304:ACAGC:A	acceptor_gain	1.0000
10:93074305:C:G	acceptor_gain	1.0000
10:93074306:A:AG	acceptor_gain	1.0000
10:93074306:AGC:A	acceptor_gain	1.0000
10:93074306:AGCG:A	acceptor_gain	1.0000
10:93074307:G:GC	acceptor_gain	1.0000
10:93074307:GC:G	acceptor_gain	1.0000
10:93074307:GCG:G	acceptor_gain	1.0000
10:93074307:GCGG:G	acceptor_gain	1.0000
10:93074307:GCGGA:G	acceptor_gain	1.0000
10:93074769:C:A	acceptor_gain	1.0000
10:93074770:G:A	acceptor_gain	1.0000
10:93074774:CTCAG:C	acceptor_loss	1.0000
10:93074775:TCAGG:T	acceptor_loss	1.0000
10:93074776:CAGGT:C	acceptor_loss	1.0000
10:93074777:AGGT:A	acceptor_gain	1.0000
10:93074778:G:GT	acceptor_loss	1.0000
10:93074778:GGTG:G	acceptor_gain	1.0000
10:93074778:GGTGA:G	acceptor_gain	1.0000
10:93075068:GG:G	donor_gain	1.0000
10:93075069:GG:G	donor_gain	1.0000
10:93075069:GGTA:G	donor_loss	1.0000
10:93075070:G:GA	donor_loss	1.0000
10:93075071:T:G	donor_loss	1.0000
10:93075142:C:CA	acceptor_gain	1.0000

AlphaMissense

3246 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:93076991:T:A	V394D	0.998
10:93077113:T:C	F435L	0.998
10:93077115:T:A	F435L	0.998
10:93077115:T:G	F435L	0.998
10:93077203:T:A	W465R	0.998
10:93077203:T:C	W465R	0.998
10:93074073:G:T	G47W	0.997
10:93075162:G:C	R240P	0.997
10:93075851:T:C	L297P	0.997
10:93075880:A:C	S307R	0.997
10:93075882:T:A	S307R	0.997
10:93075882:T:G	S307R	0.997
10:93075886:G:C	A309P	0.997
10:93075941:G:C	R327P	0.997
10:93076629:A:T	E362V	0.997
10:93076638:G:C	R365P	0.997
10:93076984:T:A	W392R	0.997
10:93076984:T:C	W392R	0.997
10:93077050:T:C	F414L	0.997
10:93077051:T:C	F414S	0.997
10:93077052:T:A	F414L	0.997
10:93077052:T:G	F414L	0.997
10:93077129:G:T	R440M	0.997
10:93077186:T:C	L459P	0.997
10:93077267:T:C	L486P	0.997
10:93077279:T:C	F490S	0.997
10:93075887:C:A	A309D	0.996
10:93075896:T:C	L312P	0.996
10:93076999:A:C	S397R	0.996
10:93077001:T:A	S397R	0.996

dbSNP variants (sampled 300 via entrez): RS1001022495 (10:93075156 A>T), RS1001248055 (10:93076482 T>G), RS1001302064 (10:93076251 G>A,C), RS1002106717 (10:93072440 G>A,T), RS1002560975 (10:93072051 C>T), RS1003057209 (10:93072531 C>A,T), RS1003164953 (10:93072727 G>C), RS1003480401 (10:93077358 A>G), RS1004054905 (10:93071502 A>G), RS1004445483 (10:93077947 T>C), RS1004928489 (10:93077621 G>A), RS1005736535 (10:93077940 C>G), RS1005873001 (10:93076365 T>C), RS1006070001 (10:93075938 T>A,C), RS1007100912 (10:93071959 A>G)

Disease associations

OMIM: gene MIM:602239 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

68 associations (top):

Study	Trait	p-value
GCST000758_4	Triglycerides	2.000000e-08
GCST001858_14	Refractive error	1.000000e-11
GCST002216_12	Triglycerides	2.000000e-11
GCST003372_50	Glomerular filtration rate (creatinine)	8.000000e-08
GCST004237_9	Triglyceride levels	3.000000e-12
GCST004603_54	Platelet count	9.000000e-11
GCST004607_119	Plateletcrit	9.000000e-11
GCST005170_26	Intraocular pressure	5.000000e-11
GCST005407_1	Glaucoma (primary open-angle)	2.000000e-06
GCST005580_136	Intraocular pressure	1.000000e-36
GCST005580_198	Intraocular pressure	9.000000e-27
GCST005989_21	Serum total protein levels	4.000000e-08
GCST005991_23	Platelet count	1.000000e-11
GCST006003_19	Triglyceride levels	4.000000e-16
GCST006291_67	Spherical equivalent or myopia (age of diagnosis)	3.000000e-10
GCST006979_599	Heel bone mineral density	2.000000e-13
GCST007344_82	Estimated glomerular filtration rate	1.000000e-08
GCST007931_7	Medication use (HMG CoA reductase inhibitors)	4.000000e-10
GCST008058_85	Estimated glomerular filtration rate	1.000000e-21
GCST008059_87	Estimated glomerular filtration rate	9.000000e-20
GCST008062_34	Blood urea nitrogen levels	3.000000e-09
GCST008070_32	HDL cholesterol levels	2.000000e-09
GCST008074_118	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-12
GCST008074_3	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-12
GCST008074_42	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-25
GCST008075_110	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-16
GCST008075_125	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-06
GCST008075_202	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-06
GCST008075_74	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-08
GCST008076_25	Triglyceride levels	2.000000e-18

EFO canonical traits (18, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0004695	intraocular pressure measurement
EFO:0004847	age at onset
EFO:0009270	heel bone mineral density
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0007778	urinary albumin to creatinine ratio
EFO:0006939	cup-to-disc ratio measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004327	electrocardiography
EFO:0006781	coffee consumption measurement
EFO:0010091	tea consumption measurement
EFO:0007989	monocyte percentage of leukocytes
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5141 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 136,276 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1023	BEXAROTENE	4	40,951
CHEMBL157101	KETOCONAZOLE	4	75,361
CHEMBL25202	TAMIBAROTENE	4	5,139
CHEMBL389433	LIAROZOLE	2	14,636
CHEMBL459505	TALAROZOLE	2	189

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — CYP24, CYP26 and CYP27 families

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 5 [PMID: 21838328]	Inhibition	9.46	pIC50
R116010	Inhibition	8.4	pIC50
liarozole	Inhibition	5.7	pIC50

Binding affinities (BindingDB)

15 measured of 25 human assays (26 total across all organisms); most potent 15 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[4-[2-(dimethylamino)-1-imidazol-1-ylpropyl]phenyl]-1,3-benzothiazol-2-amine	IC50	4.3 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
R115866	EC50	5 nM
1-[4-[4-[[2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]ethanone	IC50	127 nM	US-9394290: Selective CYP11B1 inhibitors for the treatment of cortisol dependent diseases
Liazal	IC50	1900 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
4-[2-hydroxy-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethoxy]benzoic acid	IC50	3250 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
4-[(2E)-2-hydroxyimino-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethoxy]benzoic acid	IC50	3900 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
4-[2-oxo-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethoxy]benzoic acid	IC50	4400 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid	IC50	5600 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
4-(1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene-7-carboxamido)benzoic acid	IC50	6500 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
6-[2-(4,4-dimethyl-2,3-dihydrothiochromen-6-yl)ethynyl]pyridine-3-carboxylic acid	IC50	7600 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
methyl 4-[(2Z)-2-hydroxyimino-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethoxy]benzoate	IC50	9900 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
4-((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)ethynyl)benzoic acid	IC50	10500 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
3-fluoro-4-[[2-hydroxy-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)acetyl]amino]benzoic acid	IC50	14800 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
BMS753	IC50	40200 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase
methyl 4-[(2E)-2-hydroxyimino-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethoxy]benzoate	IC50	42500 nM	US-9963439: Specific inhibitors of cytochrome P450 26 retinoic acid hydroxylase

ChEMBL bioactivities

246 potent at pChembl≥5 of 283 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	IC50	0.3	nM	CHEMBL1831092
9.46	IC50	0.35	nM	CHEMBL1831083
9.46	IC50	0.35	nM	CHEMBL1831092
8.89	IC50	1.3	nM	CHEMBL208443
8.85	IC50	1.4	nM	CHEMBL205862
8.80	IC50	1.6	nM	CHEMBL207304
8.62	IC50	2.4	nM	CHEMBL57765
8.52	IC50	3	nM	CHEMBL1766005
8.52	IC50	3	nM	CHEMBL207486
8.52	IC50	3	nM	CHEMBL1766007
8.48	IC50	3.3	nM	CHEMBL368448
8.46	IC50	3.5	nM	CHEMBL426789
8.40	IC50	4	nM	CHEMBL224305
8.38	IC50	4.2	nM	CHEMBL207942
8.37	IC50	4.3	nM	CHEMBL5785788
8.30	IC50	5	nM	CHEMBL208155
8.30	IC50	5	nM	CHEMBL224305
8.29	IC50	5.1	nM	TALAROZOLE
8.28	IC50	5.2	nM	CHEMBL223072
8.24	IC50	5.7	nM	CHEMBL2146987
8.22	IC50	6	nM	CHEMBL359627
8.22	IC50	6	nM	CHEMBL1766003
8.20	IC50	6.3	nM	CHEMBL426789
8.20	IC50	6.3	nM	CHEMBL57765
8.17	IC50	6.7	nM	CHEMBL2147090
8.15	IC50	7	nM	CHEMBL181309
8.14	IC50	7.3	nM	CHEMBL377177
8.10	IC50	8	nM	CHEMBL1766001
8.10	IC50	8	nM	CHEMBL179550
8.10	IC50	8	nM	CHEMBL1766006
8.05	IC50	9	nM	CHEMBL210780
8.03	IC50	9.4	nM	CHEMBL2146981
8.00	IC50	10	nM	CHEMBL1766000
8.00	IC50	10	nM	CHEMBL3617993
8.00	IC50	10	nM	CHEMBL223072
8.00	IC50	10	nM	CHEMBL1766008
8.00	IC50	10	nM	CHEMBL517438
7.96	IC50	10.9	nM	CHEMBL57765
7.95	IC50	11.2	nM	CHEMBL207638
7.92	IC50	12	nM	CHEMBL368448
7.92	IC50	12	nM	CHEMBL1831088
7.89	IC50	13	nM	CHEMBL2205775
7.85	IC50	14	nM	CHEMBL2146986
7.84	IC50	14.4	nM	CHEMBL360072
7.80	IC50	16	nM	CHEMBL2146980
7.80	IC50	16	nM	CHEMBL178474
7.75	IC50	18	nM	CHEMBL181309
7.72	IC50	19	nM	CHEMBL362412
7.70	IC50	20	nM	CHEMBL360771
7.70	IC50	20	nM	CHEMBL208154

PubChem BioAssay actives

205 with measured affinity, of 318 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
methyl 2,2-dimethyl-3-[4-(naphthalen-2-ylamino)phenyl]-3-(1,2,4-triazol-1-yl)propanoate	619521: Inhibition of human CYP26A1 assessed using [11,12-3H]ATRA as substrate by scintillation counting	ic50	0.0003	uM
ethyl 3-imidazol-1-yl-2,2-dimethyl-3-[4-(naphthalen-2-ylamino)phenyl]propanoate	619521: Inhibition of human CYP26A1 assessed using [11,12-3H]ATRA as substrate by scintillation counting	ic50	0.0003	uM
3-[6-[(1R,2R)-2-(dimethylamino)-1-imidazol-1-ylbutyl]naphthalen-2-yl]oxy-2,2-dimethylpropanoic acid	264870: Inhibition of CYP26 expressed in human T47D cell line	ic50	0.0013	uM
1-[[6-[(1R,2R)-2-(diethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]cyclopentane-1-carboxylic acid	264870: Inhibition of CYP26 expressed in human T47D cell line	ic50	0.0014	uM
1-[[6-[(1R,2R)-1-imidazol-1-yl-2-[methyl(propan-2-yl)amino]propyl]naphthalen-2-yl]oxymethyl]cyclopentane-1-carboxylic acid	264870: Inhibition of CYP26 expressed in human T47D cell line	ic50	0.0016	uM
(2E,4E,6E,8E)-9-(3-imidazol-1-yl-2,6,6-trimethylcyclohexen-1-yl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid	282369: Inhibition of ATRA-induced CYP26 in human T47D cell microsome assessed as ATRA metabolism using [11.12-3H]-ATRA	ic50	0.0024	uM
3-[6-[(1R,2R)-1-imidazol-1-yl-2-[methyl(propan-2-yl)amino]propyl]naphthalen-2-yl]oxy-2,2-dimethylpropanoic acid	264870: Inhibition of CYP26 expressed in human T47D cell line	ic50	0.0030	uM
methyl 3-[4-[(6-hydroxynaphthalen-2-yl)amino]phenyl]-3-imidazol-1-yl-2,2-dimethylpropanoate	593893: Inhibition of CYP26A1 in human MCF7 cell microsomes using [3H]ATRA after 1 hr by scintillation counting	ic50	0.0030	uM
methyl 3-imidazol-1-yl-2,2-dimethyl-3-[4-(naphthalen-2-ylamino)phenyl]propanoate	1248099: Inhibition of CYP26A1 (unknown origin)	ic50	0.0030	uM
4-[[6-[2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]benzoic acid	241210: Potency towards cytochrome P 450 26 enzyme activity	ic50	0.0033	uM
3-[[6-[2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]benzoic acid	241210: Potency towards cytochrome P 450 26 enzyme activity	ic50	0.0035	uM
N-[4-[(1R)-2-ethyl-1-(1,2,4-triazol-1-yl)butyl]phenyl]-1,3-benzothiazol-2-amine	1248099: Inhibition of CYP26A1 (unknown origin)	ic50	0.0040	uM
1-[[6-[(1R,2R)-2-[ethyl(methyl)amino]-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]cyclopentane-1-carboxylic acid	264870: Inhibition of CYP26 expressed in human T47D cell line	ic50	0.0042	uM
3-[6-[(1R,2R)-2-(diethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxy-2,2-dimethylpropanoic acid	264870: Inhibition of CYP26 expressed in human T47D cell line	ic50	0.0050	uM
N-[4-[2-ethyl-1-(1,2,4-triazol-1-yl)butyl]phenyl]-1,3-benzothiazol-2-amine	1799732: Cell Assay from Article 10.1080/14756360802218334: “Design and synthesis of substituted imidazole and triazole N-phenylbenzo[d]oxazolamine inhibitors of retinoic acid metabolizing enzyme CYP26.”	ec50	0.0050	uM
(2E,4E,6E,8E)-1-imidazol-1-yl-9-(3-imidazol-1-yl-2,6,6-trimethylcyclohexen-1-yl)-3,7-dimethylnona-2,4,6,8-tetraen-1-one	282369: Inhibition of ATRA-induced CYP26 in human T47D cell microsome assessed as ATRA metabolism using [11.12-3H]-ATRA	ic50	0.0052	uM
methyl 3-[4-[(6-bromo-3-pyridinyl)amino]phenyl]-3-imidazol-1-yl-2,2-dimethylpropanoate	687394: Inhibition of CYP26A1-mediated retinoic acid metabolism in human MCF7 cell microsomes using [3H]ATRA as substrate after 1 hr by scintillation counting	ic50	0.0057	uM
4-[[6-[2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]benzonitrile	241210: Potency towards cytochrome P 450 26 enzyme activity	ic50	0.0060	uM
methyl 3-imidazol-1-yl-2,2-dimethyl-3-[4-(naphthalen-1-ylamino)phenyl]propanoate	593893: Inhibition of CYP26A1 in human MCF7 cell microsomes using [3H]ATRA after 1 hr by scintillation counting	ic50	0.0060	uM
methyl 3-[4-(1,3-benzodioxol-5-ylamino)phenyl]-2,2-dimethyl-3-(1,2,4-triazol-1-yl)propanoate	687394: Inhibition of CYP26A1-mediated retinoic acid metabolism in human MCF7 cell microsomes using [3H]ATRA as substrate after 1 hr by scintillation counting	ic50	0.0067	uM
methyl 3-[[6-[2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]benzoate	241210: Potency towards cytochrome P 450 26 enzyme activity	ic50	0.0070	uM
1-[[6-[(1R,2R)-2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]cyclopentane-1-carboxylic acid	264870: Inhibition of CYP26 expressed in human T47D cell line	ic50	0.0073	uM
2-[4-[[6-[2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]phenoxy]acetic acid	241210: Potency towards cytochrome P 450 26 enzyme activity	ic50	0.0080	uM
methyl 3-imidazol-1-yl-3-[4-[(6-methoxynaphthalen-2-yl)amino]phenyl]-2,2-dimethylpropanoate	593893: Inhibition of CYP26A1 in human MCF7 cell microsomes using [3H]ATRA after 1 hr by scintillation counting	ic50	0.0080	uM
methyl 3-[4-(1,3-benzodioxol-5-ylamino)phenyl]-3-imidazol-1-yl-2,2-dimethylpropanoate	593893: Inhibition of CYP26A1 in human MCF7 cell microsomes using [3H]ATRA after 1 hr by scintillation counting	ic50	0.0080	uM
3-[6-[(1R,2R)-2-[ethyl(methyl)amino]-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxy-2,2-dimethylpropanoic acid	264870: Inhibition of CYP26 expressed in human T47D cell line	ic50	0.0090	uM
methyl 3-imidazol-1-yl-2,2-dimethyl-3-[4-[4-(trifluoromethyl)anilino]phenyl]propanoate	687394: Inhibition of CYP26A1-mediated retinoic acid metabolism in human MCF7 cell microsomes using [3H]ATRA as substrate after 1 hr by scintillation counting	ic50	0.0094	uM
methyl 3-(4-anilinophenyl)-3-imidazol-1-yl-2,2-dimethylpropanoate	593893: Inhibition of CYP26A1 in human MCF7 cell microsomes using [3H]ATRA after 1 hr by scintillation counting	ic50	0.0100	uM
methyl 3-[4-(1,3-benzoxazol-2-ylamino)phenyl]-3-imidazol-1-yl-2,2-dimethylpropanoate	593893: Inhibition of CYP26A1 in human MCF7 cell microsomes using [3H]ATRA after 1 hr by scintillation counting	ic50	0.0100	uM
N-[4-[2-(dimethylamino)-1-(1,2,4-triazol-1-yl)propyl]phenyl]-1,3-benzothiazol-2-amine	1248099: Inhibition of CYP26A1 (unknown origin)	ic50	0.0100	uM
N-[4-[(1R,2R)-2-(dimethylamino)-1-imidazol-1-ylpropyl]phenyl]-1,3-benzothiazol-2-amine	593893: Inhibition of CYP26A1 in human MCF7 cell microsomes using [3H]ATRA after 1 hr by scintillation counting	ic50	0.0100	uM
1-[[6-[(1R,2R)-2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]cyclohexane-1-carboxylic acid	264870: Inhibition of CYP26 expressed in human T47D cell line	ic50	0.0112	uM
3-imidazol-1-yl-N,2,2-trimethyl-3-[4-(naphthalen-2-ylamino)phenyl]propanamide	619521: Inhibition of human CYP26A1 assessed using [11,12-3H]ATRA as substrate by scintillation counting	ic50	0.0120	uM
methyl 3-(4-anilinophenyl)-2,2-dimethyl-3-(1,2,4-triazol-1-yl)propanoate	713753: Inhibition of CYP26A1 in human MCF7 cell microsomes using [3H]ATRA as substrate after 1 hr by scintillation counter analysis	ic50	0.0130	uM
methyl 3-imidazol-1-yl-3-[4-(4-methoxy-3,5-dimethylanilino)phenyl]-2,2-dimethylpropanoate	687394: Inhibition of CYP26A1-mediated retinoic acid metabolism in human MCF7 cell microsomes using [3H]ATRA as substrate after 1 hr by scintillation counting	ic50	0.0140	uM
3-[[6-[2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]-N,N-dimethylbenzamide	241210: Potency towards cytochrome P 450 26 enzyme activity	ic50	0.0144	uM
methyl 4-[[6-[2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]benzoate	241210: Potency towards cytochrome P 450 26 enzyme activity	ic50	0.0160	uM
methyl 3-imidazol-1-yl-2,2-dimethyl-3-[4-(4-methylanilino)phenyl]propanoate	687394: Inhibition of CYP26A1-mediated retinoic acid metabolism in human MCF7 cell microsomes using [3H]ATRA as substrate after 1 hr by scintillation counting	ic50	0.0160	uM
methyl 2-[4-[[6-[2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]phenoxy]acetate	241210: Potency towards cytochrome P 450 26 enzyme activity	ic50	0.0190	uM
3-[6-[2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxy-2,2-dimethylpropanoic acid	241210: Potency towards cytochrome P 450 26 enzyme activity	ic50	0.0200	uM
3-[6-[(1R,2R)-2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxy-2,2-dimethylpropanoic acid	264870: Inhibition of CYP26 expressed in human T47D cell line	ic50	0.0200	uM
1-[6-(2,2-dimethylpropoxy)naphthalen-2-yl]-1-imidazol-1-yl-N,N-dimethylpropan-2-amine	241210: Potency towards cytochrome P 450 26 enzyme activity	ic50	0.0214	uM
(2E,4E,6E,8E)-N-(4-hydroxyphenyl)-9-(3-imidazol-1-yl-2,6,6-trimethylcyclohexen-1-yl)-3,7-dimethylnona-2,4,6,8-tetraenamide	282368: Inhibition of ATRA-induced CYP26 in human T47D cells assessed as ATRA metabolism using [11.12-3H]-ATRA	ic50	0.0240	uM
2-[4-[[6-[2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]phenyl]acetic acid	241210: Potency towards cytochrome P 450 26 enzyme activity	ic50	0.0250	uM
3-[6-[(1R)-2-(dimethylamino)-1-imidazol-1-yl-2-methylpropyl]naphthalen-2-yl]oxy-2,2-dimethylpropanoic acid	264870: Inhibition of CYP26 expressed in human T47D cell line	ic50	0.0260	uM
methyl (2R,3R)-3-(4-anilinophenyl)-3-imidazol-1-yl-2-methylpropanoate	593893: Inhibition of CYP26A1 in human MCF7 cell microsomes using [3H]ATRA after 1 hr by scintillation counting	ic50	0.0260	uM
1-imidazol-1-yl-N,N-dimethyl-1-[6-[[4-[(2-methylpropan-2-yl)oxy]phenyl]methoxy]naphthalen-2-yl]propan-2-amine	241210: Potency towards cytochrome P 450 26 enzyme activity	ic50	0.0340	uM
3-[6-[(1R,2R)-1-imidazol-1-yl-2-morpholin-4-ylpropyl]naphthalen-2-yl]oxy-2,2-dimethylpropanoic acid	264870: Inhibition of CYP26 expressed in human T47D cell line	ic50	0.0340	uM
1-[[6-[(1R,2R)-2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxymethyl]cyclopropane-1-carboxylic acid	264870: Inhibition of CYP26 expressed in human T47D cell line	ic50	0.0347	uM
3-[6-[2-(dimethylamino)-1-imidazol-1-ylpropyl]naphthalen-2-yl]oxy-N,N,2,2-tetramethylpropanamide	241210: Potency towards cytochrome P 450 26 enzyme activity	ic50	0.0350	uM

CTD chemical–gene interactions

89 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases response to substance, decreases activity, affects binding, increases chemical synthesis, decreases chemical synthesis (+11 more)	30
Valproic Acid	affects expression, decreases expression, increases methylation, affects cotreatment, increases expression	8
Ketoconazole	decreases reaction, increases chemical synthesis, decreases response to substance, decreases activity, decreases chemical synthesis (+3 more)	6
liarozole	increases expression, increases reaction, decreases activity, affects cotreatment	4
4-oxoretinoic acid	increases expression, increases chemical synthesis, increases metabolic processing, decreases reaction, decreases activity (+2 more)	3
methylmercuric chloride	increases expression	3
4-hydroxyretinoic acid	decreases chemical synthesis, decreases metabolic processing, increases expression, increases chemical synthesis, increases metabolic processing (+2 more)	3
Vitamin A	affects cotreatment, increases expression	3
Isotretinoin	increases expression	3
sodium arsenite	affects expression, increases expression	2
AGN 193109	decreases reaction, increases expression	2
entinostat	increases expression, affects cotreatment	2
R 115866	decreases activity, decreases chemical synthesis, decreases metabolic processing, decreases reaction, increases metabolic processing	2
R116010	affects cotreatment, increases expression, increases reaction	2
Alitretinoin	increases expression	2
Cisplatin	affects expression, decreases response to substance	2
Endosulfan	decreases reaction, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Progesterone	affects cotreatment, increases expression	2
Smoke	increases abundance, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
beta Carotene	increases expression	2
bisphenol F	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
terbufos	increases methylation	1
trichostatin A	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1

ChEMBL screening assays

35 unique, capped per target: 28 binding, 6 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1768149	Binding	Inhibition of CYP26A1 in human MCF7 cell microsomes using [3H]ATRA after 1 hr by scintillation counting	Small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26): synthesis and biological evaluation of imidazole methyl 3-(4-(aryl-2-ylamino)phenyl)propanoates. — J Med Chem
CHEMBL853200	Functional	Inhibition of CYP26 expressed in human T47D cell line	3-[6-(2-Dimethylamino-1-imidazol-1-yl-butyl)-naphthalen-2-yloxy]-2,2-dimethyl-propionic acid as a highly potent and selective retinoic acid metabolic blocking agent. — Bioorg Med Chem Lett
CHEMBL920016	ADMET	Inhibition of CYP26A1 in human MCF7 cells assessed as all-trans retinoic acid metabolism	Novel tetralone-derived retinoic acid metabolism blocking agents: synthesis and in vitro evaluation with liver microsomal and MCF-7 CYP26A1 cell assays. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.