AKR1B10

Summary

AKR1B10 (aldo-keto reductase family 1 member B10, HGNC:382) is a protein-coding gene on chromosome 7q33, encoding Aldo-keto reductase family 1 member B10 (O60218). Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols.

This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. This member can efficiently reduce aliphatic and aromatic aldehydes, and it is less active on hexoses. It is highly expressed in adrenal gland, small intestine, and colon, and may play an important role in liver carcinogenesis.

Source: NCBI Gene 57016 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 69 total
• Druggable target: yes — 23 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_020299

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:382
Approved symbol	AKR1B10
Name	aldo-keto reductase family 1 member B10
Location	7q33
Locus type	gene with protein product
Status	Approved
Aliases	AKR1B12, ARL-1, HIS, ARL1, HSI, ALDRLn
Ensembl gene	ENSG00000198074
Ensembl biotype	protein_coding
OMIM	604707
Entrez	57016

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000359579, ENST00000475559, ENST00000496435, ENST00000498818, ENST00000898850, ENST00000898851, ENST00000898852, ENST00000948554, ENST00000948555, ENST00000948556, ENST00000948557

RefSeq mRNA: 1 — MANE Select: NM_020299 NM_020299

CCDS: CCDS5832

Canonical transcript exons

ENST00000359579 — 10 exons

Exon	Start	End
ENSE00001425200	134527567	134527977
ENSE00002457488	134536650	134536772
ENSE00002514637	134537051	134537157
ENSE00003503913	134531908	134532024
ENSE00003545655	134538194	134538277
ENSE00003558271	134541047	134541412
ENSE00003572736	134533004	134533081
ENSE00003612580	134530643	134530810
ENSE00003634681	134538935	134539017
ENSE00003678042	134537580	134537661

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 99.85.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4356 / max 86.1247, expressed in 93 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81257	0.2386	73
81256	0.1155	35
81255	0.0447	14
81254	0.0137	7
204781	0.0129	8
81258	0.0102	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.85	gold quality
ileal mucosa	UBERON:0000331	99.59	gold quality
gingiva	UBERON:0001828	99.27	gold quality
gingival epithelium	UBERON:0001949	99.23	gold quality
mucosa of transverse colon	UBERON:0004991	98.91	gold quality
gall bladder	UBERON:0002110	98.31	gold quality
tongue squamous epithelium	UBERON:0006919	98.27	gold quality
pancreatic ductal cell	CL:0002079	97.97	gold quality
mucosa of stomach	UBERON:0001199	97.84	gold quality
cervix squamous epithelium	UBERON:0006922	97.78	gold quality
squamous epithelium	UBERON:0006914	97.61	gold quality
lower esophagus mucosa	UBERON:0035834	97.45	gold quality
esophagus mucosa	UBERON:0002469	97.38	gold quality
colonic mucosa	UBERON:0000317	97.32	gold quality
islet of Langerhans	UBERON:0000006	97.15	gold quality
cervix epithelium	UBERON:0004801	96.92	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.92	gold quality
esophagus squamous epithelium	UBERON:0006920	96.89	gold quality
epithelium of esophagus	UBERON:0001976	96.10	gold quality
duodenum	UBERON:0002114	96.03	gold quality
pylorus	UBERON:0001166	95.21	gold quality
mammalian vulva	UBERON:0000997	95.02	gold quality
rectum	UBERON:0001052	94.35	gold quality
pharyngeal mucosa	UBERON:0000355	93.50	gold quality
body of tongue	UBERON:0011876	93.44	gold quality
jejunum	UBERON:0002115	93.01	gold quality
body of stomach	UBERON:0001161	91.32	gold quality
penis	UBERON:0000989	91.31	gold quality
small intestine	UBERON:0002108	90.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.35	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	5039.31
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPG, ETS1, JUN, NFE2L2, NR5A1, SP1, TP53

miRNA regulators (miRDB)

21 targeting AKR1B10, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-487B-5P	98.85	69.48	987
HSA-MIR-3192-3P	98.62	65.80	970
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-3689A-5P	98.35	70.12	1049
HSA-MIR-3689B-5P	98.35	70.12	1049
HSA-MIR-3689E	98.35	70.12	1049
HSA-MIR-3689F	98.35	70.08	1052
HSA-MIR-3151-3P	97.80	66.16	479
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-6511A-3P	97.60	66.61	713
HSA-MIR-6511B-3P	97.60	66.61	713
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-4298	97.26	66.59	765
HSA-MIR-383-5P	96.86	67.55	820

Literature-anchored findings (GeneRIF, showing 40)

• role as efficient retinal reductase and consequence in retinoid metabolism (PMID:12732097)
• Z-2 allele of the aldose reductase gene is a risk factor for the development of diabetic retinopathy in a group of Caucasian participants with Type 2 diabetes. (PMID:15745835)
• Aldose reductase might play a role in cell cycle progression of A549 tumor cells. (PMID:15928807)
• Data show tha activation of protein kinase C and tyrosine kinase by 12-O-tetradecanoylphorbol-13-acetate elicits increased promoter activity of aldose reductase gene via nuclear factor kappaB. (PMID:15936242)
• Data show that human aldose reductase increases atherosclerosis in diabetic mice. (PMID:16127462)
• crystallographic analysis of human aldose reductase (PMID:16204895)
• TIMP3, DAPK1 and AKR1B10 are important for squamous cell lung cancer tumorogenesis while AKR1B10 is potential oncogene whereas TIMP3 and DAPK1 are potential tumor suppressor genes. (PMID:17209433)
• Inhibition of aldose reductase prevented TNF-alpha-induced activation of protein kinase C and NF-kappaB which resulted in the abrogation of Cox-2 mRNA and protein expression (PMID:17300864)
• associated with tumor recurrence after surgery and keratinization of squamous cell carcinoma in cervical cancer but not endometrial cancer (PMID:17425679)
• AKR1B10 may regulate cell proliferation and cellular response to additional carbonyl stress (PMID:17597105)
• a tyrosine residue located in the catalytic site (Tyr48) is a likely candidate to act as proton acceptor upon inhibitor binding, as it occurs deprotonated to a remarkable extent if only the cofactor NADP+ is bound (PMID:17905306)
• AKR1B10 regulates the stability of acetyl-CoA carboxylase-alpha and is a novel regulator of the biosynthesis of fatty acid, an essential component of the cell membrane, in breast cancer cells (PMID:18056116)
• structural analysis of the high all-trans-retinaldehyde reductase activity of the tumor marker AKR1B10 (PMID:18087047)
• The reaction of C299S mutant AKR1B10 is inhibited by fenofibric acid, but manifests pure non-competitive inhibition kinetics that are different from those demonstrated for the wild-type enzyme. (PMID:18325492)
• AKR1B10 might be useful as a new marker for identification of high lung cancer risk patients in usual interstitial pneumonia. (PMID:18358633)
• Results describe cathepsin D and aldo-keto reductase 1C2 and 1B10 dysregulation in Barrett’s esophagus and esophageal adenocarcinoma. (PMID:18396902)
• AKR1B10 may play a greater role in lung carcinogenesis through dysregulation of retinoic acid homeostasis than through oxidation of PAH trans-dihydrodiols. (PMID:18788756)
• substrate specificity of AKR1B10 is drastically affected by mutation of residue 299 from Cys to Ser (PMID:19028477)
• The results demonstrated that AKR1B10 consists of 10 exons and 9 introns, stretching approximately 13.8 kb (PMID:19236911)
• novel role of AKR1B10 in controlling isoprenoid homeostasis that is important in cholesterol synthesis and cell proliferation through salvaging isoprenoid alcohols, as well as its metabolic regulation by endogenous steroids (PMID:19464995)
• AKR1B10 specifically expressed in the intestine is physiologically important in protecting the host cell against dietary and lipid-derived cytotoxic carbonyls. (PMID:19563777)
• Data suggest that AKR1B10 affects cell survival through modulating lipid synthesis, mitochondrial function, and oxidative status, as well as carbonyl levels, being an important cell survival protein. (PMID:19643728)
• Transgenic aldose reductase plays a novel role regulating the signaling pathways leading to neutrophil-endothelial cell adhesion during acute lung inflammation. (PMID:20007578)
• Overexpression of AKR1B10 in early stages of well and moderately differentiated tumors and its downregulation in advanced tumors with low grade of differentiation showed that AKR1B10 may be a marker for differentiation of primary liver tumors. (PMID:20036025)
• The significant decrease of AKR1B10 mRNA in most samples of colorectal cancer could be considered as potential diagnostic marker of this type of cancer. (PMID:20586184)
• Smoking per se mediates upregulation of AKR1B10 expression in the airway epithelia of healthy smokers with no evidence of lung cancer. (PMID:20705797)
• AKR1B10 might promote proliferation, inhibit apoptosis and induce malignant transformation of hepatocytes by regulating the expression level of some tumor-related genes. (PMID:20943077)
• Nrf2 is one of the major factors involved in the AKR1B10 gene regulation (PMID:21277289)
• overexpression and silencing of AKR1B10 decreased and increased, respectively, susceptibility to cytotoxic effects of MMC and 4-hydroxy-2-nonenal, which was formed as a product of lipid peroxidation by MMC treatment. (PMID:21317765)
• the enzyme activity of AKR1B10 and AKR1B1 toward alpha, beta-unsaturated carbonyl compounds with cellular and dietary origins (PMID:21329684)
• High AKR1B10 secretion is associated with neoplasms. (PMID:21585341)
• Confirm prognostic value of AKR1B10 in hepatocellular carcinoma and conclude that high expression reflects less aggressive tumour behaviour. (PMID:21645211)
• AKR1B10 is associated with smoking and smoking-related non-small-cell lung cancer. (PMID:21672310)
• AKR1B10 overexpression is a prominent feature in both hereditary and sporadic papillary renal cell carcinoma and is upregulated in cell lines carrying a fumarate hydratase mutation. (PMID:22014576)
• our data suggest that post-chemotherapy AKR1B10 expression may be associated with a poor prognosis in patients who received carboplatin-gemcitabine combination chemotherapy and underwent cystectomy (PMID:22198799)
• AKR1B10 is a unique enzyme involved in pancreatic carcinogenesis possibly via modulation of cell apoptosis and protein prenylation. (PMID:22222635)
• results suggest that AKR1B10 is up-regulated by EGF and insulin through AP-1 mitogenic signalling and may be implicated in hepatocarcinogenesis (PMID:22329800)
• AKR1B10 was the most efficient catalyst of the stoichiometric two-electron reduction of BQ. (PMID:22498646)
• AKR1B10 was up-regulated in association with serum alpha-fetoprotein, and was an independent risk factor for hepatocellular carcinoma in chronic hepatitis C patients. (PMID:22681639)
• The gene expression of AKR1B10 at the mRNA level was significantly increased. (PMID:23146748)

Cross-species orthologs

24 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:110366	ENSDARG00000004167
danio_rerio	akr1a1a	ENSDARG00000035257
danio_rerio	zgc:110782	ENSDARG00000044544
danio_rerio	zgc:101765	ENSDARG00000054934
danio_rerio	zgc:56622	ENSDARG00000099728
mus_musculus	Akr1b8	ENSMUSG00000029762
mus_musculus	Akr1b7	ENSMUSG00000052131
mus_musculus	Akr1b10	ENSMUSG00000061758
rattus_norvegicus	Akr1b8	ENSRNOG00000009734
rattus_norvegicus	Akr1b7	ENSRNOG00000009875
rattus_norvegicus	Akr1b10	ENSRNOG00000027433
drosophila_melanogaster	CG6083	FBGN0036183
drosophila_melanogaster	CG18547	FBGN0037973
drosophila_melanogaster	CG3397	FBGN0037975
caenorhabditis_elegans		WBGENE00003176
caenorhabditis_elegans		WBGENE00009980
caenorhabditis_elegans		WBGENE00009981
caenorhabditis_elegans		WBGENE00012722
caenorhabditis_elegans		WBGENE00012723
caenorhabditis_elegans		WBGENE00015307
caenorhabditis_elegans		WBGENE00015564
caenorhabditis_elegans		WBGENE00015565
caenorhabditis_elegans		WBGENE00016985
caenorhabditis_elegans		WBGENE00022887

Paralogs (16): AKR7A2 (ENSG00000053371), KCNAB2 (ENSG00000069424), AKR1B1 (ENSG00000085662), AKR1A1 (ENSG00000117448), AKR1D1 (ENSG00000122787), AKR1C2 (ENSG00000151632), AKR7A3 (ENSG00000162482), AKR1E2 (ENSG00000165568), KCNAB1 (ENSG00000169282), KCNAB3 (ENSG00000170049), AKR1C1 (ENSG00000187134), AKR1C3 (ENSG00000196139), AKR1C4 (ENSG00000198610), AKR7L (ENSG00000211454), AKR1B15 (ENSG00000227471), AKR1C8 (ENSG00000264006)

Protein

Protein identifiers

Aldo-keto reductase family 1 member B10 — O60218 (reviewed: O60218)

Alternative names: ARL-1, Aldose reductase-like, Aldose reductase-related protein, Small intestine reductase

All UniProt accessions (1): O60218

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays strong enzymatic activity toward all-trans-retinal, 9-cis-retinal, and 13-cis-retinal. Plays a critical role in detoxifying dietary and lipid-derived unsaturated carbonyls, such as crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, trans-2,4-hexadienal and their glutathione-conjugates carbonyls (GS-carbonyls). Displays no reductase activity towards glucose.

Subcellular location. Lysosome. Secreted.

Tissue specificity. Found in many tissues. Highly expressed in small intestine, colon and adrenal gland.

Activity regulation. Retinaldehyde reductase activity is inhibited by tolrestat.

Induction. Overexpressed in certain types of cancers, including hepatocellular carcinoma and lung cancer associated with tobacco smoking.

Pathway. Cofactor metabolism; retinol metabolism.

Miscellaneous. Has no counterpart in murine and rat species.

Similarity. Belongs to the aldo/keto reductase family.

RefSeq proteins (1): NP_064695* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018170	Aldo/ket_reductase_CS	Conserved_site
IPR020471	AKR	Family
IPR023210	NADP_OxRdtase_dom	Domain
IPR036812	NAD(P)_OxRdtase_dom_sf	Homologous_superfamily

Pfam: PF00248

Enzyme classification (BRENDA):

• EC 1.1.1.21 — aldose reductase (BRENDA: 36 organisms, 259 substrates, 1272 inhibitors, 280 Km, 134 kcat entries)

Substrate kinetics (BRENDA)

122 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DL-GLYCERALDEHYDE	0.02–730.2	42
D-XYLOSE	2–1340	21
D-GALACTOSE	40–572	11
D-GLUCURONATE	0.152–19.2	11
D-GLUCOSE	47.3–281	10
NADPH	0.0032–85	8
BENZALDEHYDE	0.0097–3.3	5
L-XYLOSE	100–1190	5
METHYLGLYOXAL	0.112–6.3	5
4-NITROBENZALDEHYDE	0.002–0.0035	4
D-LYXOSE	479.2–2740	4
D-RIBOSE	7–377	4
GLYOXAL	1.28–70	4
PYRIDINE-3-ALDEHYDE	0.012–4.5	4
D-ARABINOSE	110–448.4	3

Catalyzed reactions (Rhea), 11 shown:

• allyl alcohol + NADP(+) = acrolein + NADPH + H(+) (RHEA:12168)
• all-trans-retinol + NADP(+) = all-trans-retinal + NADPH + H(+) (RHEA:25033)
• 9-cis-retinol + NADP(+) = 9-cis-retinal + NADPH + H(+) (RHEA:54916)
• 13-cis-retinol + NADP(+) = 13-cis-retinal + NADPH + H(+) (RHEA:54920)
• a 4-hydroxynonen-1-ol + NADP(+) = a 4-hydroxynonenal + NADPH + H(+) (RHEA:58336)
• (E)-4-hydroxynon-2-en-1-ol + NADP(+) = (E)-4-hydroxynon-2-enal + NADPH + H(+) (RHEA:58416)
• prenol + NADP(+) = 3-methyl-2-butenal + NADPH + H(+) (RHEA:58420)
• (E)-hex-2-en-1-ol + NADP(+) = (E)-hex-2-enal + NADPH + H(+) (RHEA:58424)
• (E,E)-2,4-hexadien-1-ol + NADP(+) = (E,E)-2,4-hexadienal + NADPH + H(+) (RHEA:58428)
• (E)-4-oxonon-2-en-1-ol + NADP(+) = (E)-4-oxonon-2-enal + NADPH + H(+) (RHEA:58432)
• 4-methylpentan-1-ol + NADP(+) = 4-methylpentanal + NADPH + H(+) (RHEA:58436)

UniProt features (52 total): helix 16, strand 12, binding site 7, sequence variant 3, mutagenesis site 3, sequence conflict 3, turn 3, modified residue 2, chain 1, active site 1, site 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
1ZUA	X-RAY DIFFRACTION	1.25
4WEV	X-RAY DIFFRACTION	1.45
5M2F	X-RAY DIFFRACTION	1.5
4GAB	X-RAY DIFFRACTION	1.6
4XZL	X-RAY DIFFRACTION	1.7
4XZN	X-RAY DIFFRACTION	1.7
4XZM	X-RAY DIFFRACTION	1.75
5LIU	X-RAY DIFFRACTION	1.75
5LIW	X-RAY DIFFRACTION	1.75
4ICC	X-RAY DIFFRACTION	1.75
4GQG	X-RAY DIFFRACTION	1.92
4GA8	X-RAY DIFFRACTION	1.94
5LIX	X-RAY DIFFRACTION	1.95
5LIK	X-RAY DIFFRACTION	2.05
5LIY	X-RAY DIFFRACTION	2.05
4I5X	X-RAY DIFFRACTION	2.1
4GQ0	X-RAY DIFFRACTION	2.1
4JII	X-RAY DIFFRACTION	2.2
4JIH	X-RAY DIFFRACTION	2.3
5Y7N	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60218-F1	97.77	0.99

Functional residue map

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

Catalytic / active sites (2): 49 (proton donor); 78 (lowers pka of active site tyr)

Ligand- & substrate-binding residues (7): 20–22; 44; 111; 160–161; 184; 210–217; 261–273

Post-translational modifications (2): 125, 263

Mutagenesis-validated functional residues (3):

Position	Phenotype
125	increased affinity and reduced catalytic activity towards all-trans-retinaldehyde.
299	decreased affinity and reduced catalytic activity towards 4-hydroxynonenal.
301	reduced catalytic activity towards all-trans-retinaldehyde.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-975634	Retinoid metabolism and transport
R-HSA-1430728	Metabolism
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-2187338	Visual phototransduction
R-HSA-6806667	Metabolism of fat-soluble vitamins
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 370 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, KOBAYASHI_EGFR_SIGNALING_24HR_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, JAEGER_METASTASIS_DN, CMYB_01, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_RETINOL_METABOLIC_PROCESS, REACTOME_MEMBRANE_TRAFFICKING, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_KETONE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, MAHAJAN_RESPONSE_TO_IL1A_DN

GO Biological Process (7): retinoid metabolic process (GO:0001523), farnesol catabolic process (GO:0016488), daunorubicin metabolic process (GO:0044597), doxorubicin metabolic process (GO:0044598), cellular detoxification of aldehyde (GO:0110095), lipid metabolic process (GO:0006629), retinol metabolic process (GO:0042572)

GO Molecular Function (10): retinal dehydrogenase (NAD+) activity (GO:0001758), aldose reductase (NADPH) activity (GO:0004032), alcohol dehydrogenase (NADP+) activity (GO:0008106), obsolete geranylgeranyl reductase activity (GO:0045550), allyl-alcohol dehydrogenase activity (GO:0047655), indanol dehydrogenase activity (GO:0047718), all-trans-retinol dehydrogenase (NADP+) activity (GO:0052650), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616)

GO Cellular Component (4): extracellular region (GO:0005576), mitochondrion (GO:0005739), lysosome (GO:0005764), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1
Metabolism	1
Sensory Perception	1
Metabolism of vitamins and cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycoside metabolic process	2
polyketide metabolic process	2
ketone metabolic process	2
primary alcohol metabolic process	2
alcohol dehydrogenase (NADP+) activity	2
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	2
cellular anatomical structure	2
cytoplasm	2
diterpenoid metabolic process	1
polyprenol catabolic process	1
sesquiterpenoid catabolic process	1
farnesol metabolic process	1
primary alcohol catabolic process	1
tertiary alcohol metabolic process	1
cellular response to aldehyde	1
cellular detoxification	1
primary metabolic process	1
retinoid metabolic process	1
hormone metabolic process	1
olefinic compound metabolic process	1
aldehyde dehydrogenase (NAD+) activity	1
alcohol dehydrogenase [NAD(P)+] activity	1
retinol metabolic process	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
intracellular membrane-bounded organelle	1
lytic vacuole	1

Protein interactions and networks

STRING

1670 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AKR1B10	MIOX	Q9UGB7	808
AKR1B10	DHRS9	Q9BPW9	765
AKR1B10	ADM2	Q7Z4H4	763
AKR1B10	AKR7A2	O43488	692
AKR1B10	MAPK8IP2	Q13387	669
AKR1B10	PARVB	Q9HBI1	668
AKR1B10	ACACA	Q13085	582
AKR1B10	AKR7A3	O95154	552
AKR1B10	ALDH3A1	P30838	545
AKR1B10	CBR1	P16152	541
AKR1B10	SORD	Q00796	521
AKR1B10	NQO1	P15559	515
AKR1B10	HSP90AA1	P07900	468
AKR1B10	HSP90AB1	P08238	468
AKR1B10	GCLC	P48506	450

IntAct

46 interactions, top by confidence:

A	B	Type	Score
ACACA	AKR1B10	psi-mi:“MI:0915”(physical association)	0.560
AKR1B10	ACACA	psi-mi:“MI:0915”(physical association)	0.560
AKR1B10	ACACA	psi-mi:“MI:0403”(colocalization)	0.560
AKR1B10	POTEF	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
AKR1D1	AKR1B10	psi-mi:“MI:0914”(association)	0.530
AKR1B10	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
AKR1B10	AKR1B15	psi-mi:“MI:0915”(physical association)	0.500
AKR1B10	VDAC1	psi-mi:“MI:0915”(physical association)	0.400
AKR1B10	rep	psi-mi:“MI:0915”(physical association)	0.370
Nedd1		psi-mi:“MI:0914”(association)	0.350
TSNAX		psi-mi:“MI:0914”(association)	0.350
Slain1	OARD1	psi-mi:“MI:0914”(association)	0.350
Jup		psi-mi:“MI:0914”(association)	0.350
PDE4DIP	A2ML1	psi-mi:“MI:0914”(association)	0.350
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
DDX19B	IGLL5	psi-mi:“MI:0914”(association)	0.350
ADCK5	AKR1B10	psi-mi:“MI:0914”(association)	0.350
INPPL1	ACTN4	psi-mi:“MI:0914”(association)	0.350
SRRT	A2ML1	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (62): AKR1B15 (Affinity Capture-MS), POTEF (Affinity Capture-MS), PCBP3 (Affinity Capture-MS), AKR1B10 (Affinity Capture-MS), AKR1B10 (Affinity Capture-MS), AKR1B10 (Affinity Capture-MS), AKR1B10 (Co-fractionation), AKR1B10 (Co-fractionation), AKR1B10 (Affinity Capture-MS), AKR1B10 (Affinity Capture-MS), AKR1B10 (Affinity Capture-MS), AKR1B10 (Affinity Capture-MS), AKR1B15 (Affinity Capture-MS), AKR1B10 (Affinity Capture-MS), AKR1B10 (Affinity Capture-MS)

ESM2 similar proteins: C9JRZ8, M9PF61, O08782, O14088, O60218, O70473, O80944, O94735, P02532, P07943, P0DXG9, P0DXH7, P14550, P15121, P15122, P16116, P17264, P21300, P28475, P31210, P31867, P38715, P45376, P45377, P47137, P50578, P51635, P51857, P78736, P80276, P82125, Q0PGJ6, Q28FD1, Q3ZCJ2, Q54NZ7, Q568L5, Q5R5D5, Q5RJP0, Q5U1Y4, Q5ZK84

Diamond homologs: A0A1D5XGW0, A0A1X9QHJ0, A0A2P1GIY9, A0A9E7S518, A0A9E7S5B9, B4F9A4, B9VRJ2, C9JRZ8, D3ZF77, E7C196, H9JTG9, M9PF61, O08782, O32210, O34678, O49133, O60218, O70473, O80944, P02532, P05980, P07943, P0DKI7, P0DXG9, P0DXH7, P14065, P14550, P15121, P15122, P16116, P17264, P17516, P21300, P23457, P23901, P26690, P28475, P31867, P42330, P45376

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2644 predictions. Top by Δscore:

Variant	Effect	Δscore
12:101396577:CCT:C	acceptor_loss	1.0000
12:101396578:C:CC	acceptor_gain	1.0000
12:101405842:A:AC	donor_gain	1.0000
12:101405843:C:CC	donor_gain	1.0000
12:101407654:C:CA	donor_gain	1.0000
12:101407663:C:A	donor_gain	1.0000
12:101407676:T:TA	donor_gain	1.0000
12:101407684:T:TA	donor_gain	1.0000
7:134530639:TCAG:T	acceptor_loss	1.0000
7:134530640:CAGT:C	acceptor_loss	1.0000
7:134530641:A:AG	acceptor_gain	1.0000
7:134530641:A:C	acceptor_loss	1.0000
7:134530642:G:GA	acceptor_gain	1.0000
7:134530642:GT:G	acceptor_gain	1.0000
7:134530642:GTC:G	acceptor_gain	1.0000
7:134530642:GTCT:G	acceptor_gain	1.0000
7:134530642:GTCTC:G	acceptor_gain	1.0000
7:134530808:AAGGT:A	donor_loss	1.0000
7:134530809:AGG:A	donor_loss	1.0000
7:134530810:GGTGC:G	donor_loss	1.0000
7:134530811:GT:G	donor_loss	1.0000
7:134533002:A:AG	acceptor_gain	1.0000
7:134533003:G:GG	acceptor_gain	1.0000
7:134536771:AG:A	donor_loss	1.0000
7:134536772:GGT:G	donor_loss	1.0000
7:134536773:G:A	donor_loss	1.0000
7:134537574:CCCTA:C	acceptor_loss	1.0000
7:134537575:CCTA:C	acceptor_loss	1.0000
7:134537576:CTAGG:C	acceptor_loss	1.0000
7:134537577:TAGG:T	acceptor_loss	1.0000

AlphaMissense

2101 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:134530810:G:C	K78N	0.998
7:134530810:G:T	K78N	0.998
7:134530805:A:C	S77R	0.996
7:134530807:C:A	S77R	0.996
7:134530807:C:G	S77R	0.996
7:134536703:T:A	N161K	0.996
7:134536703:T:G	N161K	0.996
7:134530809:A:T	K78M	0.995
7:134533076:T:A	W142R	0.995
7:134533076:T:C	W142R	0.995
7:134530708:C:A	D44E	0.994
7:134530708:C:G	D44E	0.994
7:134530809:A:C	K78T	0.994
7:134527972:T:A	W21R	0.993
7:134527972:T:C	W21R	0.993
7:134530806:G:T	S77I	0.993
7:134531911:T:A	W80R	0.993
7:134531911:T:C	W80R	0.993
7:134530680:C:A	A35D	0.992
7:134530729:T:A	N51K	0.992
7:134530729:T:G	N51K	0.992
7:134530808:A:C	K78Q	0.992
7:134536698:T:C	S160P	0.992
7:134536704:T:C	F162L	0.992
7:134536706:C:A	F162L	0.992
7:134536706:C:G	F162L	0.992
7:134538241:G:C	K263N	0.992
7:134538241:G:T	K263N	0.992
7:134539000:G:C	R297S	0.992
7:134539000:G:T	R297S	0.992

dbSNP variants (sampled 300 via entrez): RS1000376879 (7:134526815 G>A), RS1000471820 (7:134527103 C>A), RS1000656333 (7:134532357 T>A), RS1001557217 (7:134526461 G>A), RS1001820298 (7:134532024 G>C,T), RS1001961198 (7:134537276 C>G,T), RS1002035168 (7:134541520 T>C), RS1002108931 (7:134541753 C>T), RS1002351287 (7:134537083 A>G,T), RS1002664810 (7:134534883 G>T), RS1002782018 (7:134539573 T>C), RS1003396211 (7:134530335 T>C), RS1003711256 (7:134540264 A>G,T), RS1003784882 (7:134540577 T>C), RS1004003846 (7:134539355 C>G)

Disease associations

OMIM: gene MIM:604707 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002408_10	Response to methotrexate in juvenile idiopathic arthritis	5.000000e-06
GCST004747_21	Lung cancer in never smokers	7.000000e-06
GCST006087_17	Familial lung adenocarcinoma	3.000000e-06
GCST006221_1	White matter growth	9.000000e-09
GCST006630_13	Diastolic blood pressure	2.000000e-14
GCST007930_146	Medication use (agents acting on the renin-angiotensin system)	4.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006953	family history of lung cancer
EFO:0009335	white matter growth measurement
EFO:0006336	diastolic blood pressure
EFO:0009931	Agents acting on the renin-angiotensin system use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5983 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

23 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 784,902 (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
CHEMBL135	ESTRADIOL	4	123,080
CHEMBL139	DICLOFENAC	4	125,009
CHEMBL1405	ESTRONE	4	36,722
CHEMBL15770	SULINDAC	4	80,712
CHEMBL436	TOLRESTAT	4	3,768
CHEMBL509	MECLOFENAMIC ACID	4	45,809
CHEMBL56337	EPALRESTAT	4	110
CHEMBL686	MEFENAMIC ACID	4	61,835
CHEMBL145	CAFFEIC ACID	3	36,305
CHEMBL266497	SORBINIL	3	2,026
CHEMBL50	QUERCETIN	3	74,559
CHEMBL10372	ZOPOLRESTAT	2	3,266
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL169	URSOLIC ACID	2	20,825
CHEMBL2057301	SEPRANOLONE	2	452
CHEMBL230006	ENOXOLONE	2	24,361
CHEMBL23588	FLUFENAMIC ACID	2	34,797
CHEMBL273910	MINALRESTAT	2	1,586
CHEMBL284616	CHLOROGENIC ACID	2	41,945
CHEMBL44	GENISTEIN	2	44,212
CHEMBL8145	DAIDZEIN	2
CHEMBL84446	FIDARESTAT	2
CHEMBL269277	BETULINIC ACID	1

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

Binding affinities (BindingDB)

6 measured of 18 human assays (18 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-{[6-methoxy-5-(trifluoromethyl)naphthalen-1-yl]-N-methylmethanethioamido}acetic acid	IC50	1 nM
(4-oxo-3-{[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl}-3,4-dihydrophthalazin-1-yl)acetic acid	IC50	60 nM
(E)-3-(3,4-Dihydroxy-phenyl)-acrylic acid phenethyl ester	IC50	80 nM
4-acetyl-2-(2-carboxyanilino)benzoic acid	IC50	27700 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
3-[N-(4-acetylphenyl)amino]benzoic acid	IC50	38600 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
2-(5-methoxy-2-nitroanilino)benzoic acid	IC50	42700 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof

ChEMBL bioactivities

203 potent at pChembl≥5 of 236 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.89	Ki	1.3	nM	CHEMBL2440417
8.64	Ki	2.3	nM	CHEMBL4081954
8.59	Ki	2.6	nM	CHEMBL1940400
8.57	Ki	2.7	nM	CHEMBL1172665
8.46	IC50	3.5	nM	CHEMBL4089817
8.46	Ki	3.5	nM	CHEMBL1940400
8.42	Ki	3.8	nM	CHEMBL2440417
8.38	IC50	4.2	nM	CHEMBL4081954
8.33	IC50	4.7	nM	CHEMBL2440417
8.29	Ki	5.1	nM	CHEMBL1940400
8.24	Ki	5.8	nM	CHEMBL1940400
8.22	IC50	6	nM	CHEMBL1172665
8.22	IC50	6	nM	CHEMBL4060049
8.21	IC50	6.2	nM	CHEMBL1940400
8.19	IC50	6.4	nM	CHEMBL4098452
8.17	IC50	6.8	nM	CHEMBL2440422
8.15	IC50	7	nM	CHEMBL4062779
8.15	Ki	7.1	nM	CHEMBL1940400
8.12	IC50	7.6	nM	CHEMBL2440423
8.12	IC50	7.5	nM	CHEMBL4089816
8.12	Ki	7.6	nM	CHEMBL1940400
8.11	IC50	7.8	nM	CHEMBL4068704
8.08	IC50	8.3	nM	CHEMBL4071421
8.07	IC50	8.6	nM	CHEMBL2440424
8.06	IC50	8.8	nM	CHEMBL2440416
8.05	IC50	9	nM	CHEMBL1940399
8.01	IC50	9.7	nM	CHEMBL2440411
8.00	IC50	10	nM	CHEMBL1940394
8.00	IC50	10	nM	CHEMBL1171546
7.96	IC50	11	nM	CHEMBL2440415
7.96	IC50	11	nM	CHEMBL2440414
7.96	IC50	11	nM	CHEMBL4084456
7.96	IC50	11	nM	CHEMBL4071420
7.94	IC50	11.6	nM	TOLRESTAT
7.92	IC50	12	nM	CHEMBL2440428
7.92	Ki	12	nM	CHEMBL1171546
7.89	IC50	13	nM	CHEMBL2440427
7.89	IC50	13	nM	CHEMBL2440426
7.89	IC50	13	nM	CHEMBL1940396
7.89	IC50	13	nM	CHEMBL1940394
7.85	IC50	14	nM	CHEMBL2440425
7.85	IC50	14	nM	CHEMBL1940397
7.82	Ki	15	nM	ISOLITHOCHOLIC ACID
7.82	IC50	15	nM	CHEMBL1171546
7.82	Ki	15	nM	CHEMBL1940400
7.80	IC50	16	nM	CHEMBL2440413
7.80	Ki	16	nM	CHEMBL1169756
7.80	IC50	16	nM	CHEMBL1940398
7.77	IC50	17	nM	CHEMBL1940395
7.75	IC50	18	nM	CHEMBL2440412

PubChem BioAssay actives

167 with measured affinity, of 320 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
2-[[6-methoxy-5-(trifluoromethyl)naphthalene-1-carbothioyl]-methylamino]acetic acid	1802104: IC50-Activity Assay (AKR1B10) from Article 10.1021/acschembio.6b00382: “IDD388 Polyhalogenated Derivatives as Probes for an Improved Structure-Based Selectivity of AKR1B10 Inhibitors”	ic50	0.0012	uM
N-benzyl-7-hydroxy-2-(4-methoxyphenyl)iminochromene-3-carboxamide	779752: Competitive inhibition of wild-type human recombinant N-terminal His6-tagged AKR1B10 expressed in Escherichia coli using geraniol as substrate by double-reciprocal plot analysis in presence of NADP+	ki	0.0013	uM
7-hydroxy-N-[3-(4-hydroxyphenyl)propyl]-2-oxochromene-3-carboxamide	1465674: Competitive inhibition of recombinant human AKR1B10 in presence of geraniol as substrate by Lineweaver-Burk plot method	ki	0.0023	uM
3-(3-hydroxyphenyl)propyl (E)-3-(4-hydroxy-2-methoxyphenyl)prop-2-enoate	641082: Competitive inhibition at human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as inhibition of NADP+ linked geraniol oxidation by fluorescence analysis	ki	0.0026	uM
7-hydroxy-2-(4-methoxyphenyl)imino-N-pyridin-2-ylchromene-3-carboxamide	489632: Inhibition of dehydrogenase activity of N-terminal 6His-tagged AKR1B10 expressed in Escherichia coli BL21(DE3) assessed as inhibition of geraniol dehydrogenation in presence of saturating concentration of NADP+	ki	0.0027	uM
N-[3-(4-fluorophenyl)propyl]-7-hydroxy-2-oxochromene-3-carboxamide	1465658: Inhibition of recombinant human AKR1B10 using pyridine-3-aldehyde as substrate	ic50	0.0035	uM
N-[3-(3-fluorophenyl)propyl]-7-hydroxy-2-oxochromene-3-carboxamide	1465658: Inhibition of recombinant human AKR1B10 using pyridine-3-aldehyde as substrate	ic50	0.0060	uM
7-hydroxy-N-[3-(2-hydroxyphenyl)propyl]-2-oxochromene-3-carboxamide	1465658: Inhibition of recombinant human AKR1B10 using pyridine-3-aldehyde as substrate	ic50	0.0064	uM
7-hydroxy-2-(4-hydroxyphenyl)imino-N-pyridin-2-ylchromene-3-carboxamide	779756: Inhibition of human recombinant N-terminal His6-tagged AKR1B10 expressed in Escherichia coli by fluorescence assay in presence of NADPH	ic50	0.0068	uM
7-hydroxy-N-[3-(4-methylphenyl)propyl]-2-oxochromene-3-carboxamide	1465658: Inhibition of recombinant human AKR1B10 using pyridine-3-aldehyde as substrate	ic50	0.0070	uM
7-hydroxy-N-[3-(3-hydroxyphenyl)propyl]-2-(4-methoxyphenyl)iminochromene-3-carboxamide	1465658: Inhibition of recombinant human AKR1B10 using pyridine-3-aldehyde as substrate	ic50	0.0075	uM
4-[[7-hydroxy-3-(pyridin-2-ylcarbamoyl)chromen-2-ylidene]amino]benzoic acid	779756: Inhibition of human recombinant N-terminal His6-tagged AKR1B10 expressed in Escherichia coli by fluorescence assay in presence of NADPH	ic50	0.0076	uM
N-[3-(3,5-difluorophenyl)propyl]-7-hydroxy-2-oxochromene-3-carboxamide	1465658: Inhibition of recombinant human AKR1B10 using pyridine-3-aldehyde as substrate	ic50	0.0078	uM
7-hydroxy-N-[3-(3-hydroxyphenyl)propyl]-2-oxochromene-3-carboxamide	1465658: Inhibition of recombinant human AKR1B10 using pyridine-3-aldehyde as substrate	ic50	0.0083	uM
7-hydroxy-2-(4-methylphenyl)imino-N-pyridin-2-ylchromene-3-carboxamide	779756: Inhibition of human recombinant N-terminal His6-tagged AKR1B10 expressed in Escherichia coli by fluorescence assay in presence of NADPH	ic50	0.0086	uM
7-hydroxy-N-(3-hydroxypropyl)-2-(4-methoxyphenyl)iminochromene-3-carboxamide	779756: Inhibition of human recombinant N-terminal His6-tagged AKR1B10 expressed in Escherichia coli by fluorescence assay in presence of NADPH	ic50	0.0088	uM
3-(2-hydroxyphenyl)propyl (E)-3-(4-hydroxy-2-methoxyphenyl)prop-2-enoate	641086: Inhibition of human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as pyridine-3-aldehyde reduction by spectrometric analysis	ic50	0.0090	uM
7-hydroxy-2-(4-methoxyphenyl)imino-N-propan-2-ylchromene-3-carboxamide	779756: Inhibition of human recombinant N-terminal His6-tagged AKR1B10 expressed in Escherichia coli by fluorescence assay in presence of NADPH	ic50	0.0097	uM
N-cyclohexyl-7-hydroxy-2-(4-methoxyphenyl)iminochromene-3-carboxamide	779756: Inhibition of human recombinant N-terminal His6-tagged AKR1B10 expressed in Escherichia coli by fluorescence assay in presence of NADPH	ic50	0.0110	uM
7-hydroxy-N-(2-hydroxyethyl)-2-(4-methoxyphenyl)iminochromene-3-carboxamide	779756: Inhibition of human recombinant N-terminal His6-tagged AKR1B10 expressed in Escherichia coli by fluorescence assay in presence of NADPH	ic50	0.0110	uM
7-hydroxy-N-[4-(4-hydroxyphenyl)butyl]-2-oxochromene-3-carboxamide	1465658: Inhibition of recombinant human AKR1B10 using pyridine-3-aldehyde as substrate	ic50	0.0110	uM
7-hydroxy-N-[3-(4-methoxyphenyl)propyl]-2-oxochromene-3-carboxamide	1465658: Inhibition of recombinant human AKR1B10 using pyridine-3-aldehyde as substrate	ic50	0.0110	uM
2-(2,4-dimethoxyphenyl)imino-7-hydroxy-N-pyridin-2-ylchromene-3-carboxamide	489632: Inhibition of dehydrogenase activity of N-terminal 6His-tagged AKR1B10 expressed in Escherichia coli BL21(DE3) assessed as inhibition of geraniol dehydrogenation in presence of saturating concentration of NADP+	ki	0.0120	uM
7-hydroxy-2-phenylimino-N-pyridin-2-ylchromene-3-carboxamide	779756: Inhibition of human recombinant N-terminal His6-tagged AKR1B10 expressed in Escherichia coli by fluorescence assay in presence of NADPH	ic50	0.0120	uM
7-hydroxy-2-(4-iodophenyl)imino-N-pyridin-2-ylchromene-3-carboxamide	779756: Inhibition of human recombinant N-terminal His6-tagged AKR1B10 expressed in Escherichia coli by fluorescence assay in presence of NADPH	ic50	0.0130	uM
2-[4-[[7-hydroxy-3-(pyridin-2-ylcarbamoyl)chromen-2-ylidene]amino]phenyl]acetic acid	779756: Inhibition of human recombinant N-terminal His6-tagged AKR1B10 expressed in Escherichia coli by fluorescence assay in presence of NADPH	ic50	0.0130	uM
2-phenylethyl (E)-3-(4-hydroxy-2-methoxyphenyl)prop-2-enoate	641086: Inhibition of human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as pyridine-3-aldehyde reduction by spectrometric analysis	ic50	0.0130	uM
2-(3-hydroxyphenyl)ethyl (E)-3-(4-hydroxy-2-methoxyphenyl)prop-2-enoate	641086: Inhibition of human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as pyridine-3-aldehyde reduction by spectrometric analysis	ic50	0.0130	uM
2-(4-bromophenyl)imino-7-hydroxy-N-pyridin-2-ylchromene-3-carboxamide	779756: Inhibition of human recombinant N-terminal His6-tagged AKR1B10 expressed in Escherichia coli by fluorescence assay in presence of NADPH	ic50	0.0140	uM
2-(4-hydroxyphenyl)ethyl (E)-3-(4-hydroxy-2-methoxyphenyl)prop-2-enoate	641086: Inhibition of human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as pyridine-3-aldehyde reduction by spectrometric analysis	ic50	0.0140	uM
(4R)-4-[(3S,5R,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid	697009: Inhibition of reductase activity of N-terminal 6His-tagged human AKR1B10 expressed in Escherichia coli BL21(DE3) assessed as pyridine-3-aldehyde reduction	ki	0.0150	uM
2-(2,5-dimethoxyphenyl)imino-7-hydroxy-N-pyridin-2-ylchromene-3-carboxamide	489632: Inhibition of dehydrogenase activity of N-terminal 6His-tagged AKR1B10 expressed in Escherichia coli BL21(DE3) assessed as inhibition of geraniol dehydrogenation in presence of saturating concentration of NADP+	ki	0.0160	uM
7-hydroxy-2-(4-methoxyphenyl)imino-N-(2-methylpropyl)chromene-3-carboxamide	779756: Inhibition of human recombinant N-terminal His6-tagged AKR1B10 expressed in Escherichia coli by fluorescence assay in presence of NADPH	ic50	0.0160	uM
3-phenylpropyl (E)-3-(4-hydroxy-2-methoxyphenyl)prop-2-enoate	641086: Inhibition of human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as pyridine-3-aldehyde reduction by spectrometric analysis	ic50	0.0160	uM
2-(2-hydroxyphenyl)ethyl (E)-3-(4-hydroxy-2-methoxyphenyl)prop-2-enoate	641086: Inhibition of human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as pyridine-3-aldehyde reduction by spectrometric analysis	ic50	0.0170	uM
N-butyl-7-hydroxy-2-(4-methoxyphenyl)iminochromene-3-carboxamide	779756: Inhibition of human recombinant N-terminal His6-tagged AKR1B10 expressed in Escherichia coli by fluorescence assay in presence of NADPH	ic50	0.0180	uM
7-hydroxy-N-[2-(4-hydroxyphenyl)ethyl]-2-oxochromene-3-carboxamide	1465658: Inhibition of recombinant human AKR1B10 using pyridine-3-aldehyde as substrate	ic50	0.0200	uM
3-phenylpropyl (E)-3-(4-hydroxyphenyl)prop-2-enoate	641086: Inhibition of human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as pyridine-3-aldehyde reduction by spectrometric analysis	ic50	0.0210	uM
3-(4-hydroxyphenyl)propyl (E)-3-(4-hydroxy-2-methoxyphenyl)prop-2-enoate	641086: Inhibition of human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as pyridine-3-aldehyde reduction by spectrometric analysis	ic50	0.0230	uM
2-(3,4-dimethoxyphenyl)imino-7-hydroxy-N-(6-methyl-2-pyridinyl)chromene-3-carboxamide	489632: Inhibition of dehydrogenase activity of N-terminal 6His-tagged AKR1B10 expressed in Escherichia coli BL21(DE3) assessed as inhibition of geraniol dehydrogenation in presence of saturating concentration of NADP+	ki	0.0240	uM
2-[5-chloro-2-[(2,3,4,5,6-pentabromophenyl)methylcarbamoyl]phenoxy]acetic acid	1802104: IC50-Activity Assay (AKR1B10) from Article 10.1021/acschembio.6b00382: “IDD388 Polyhalogenated Derivatives as Probes for an Improved Structure-Based Selectivity of AKR1B10 Inhibitors”	ic50	0.0300	uM
2-[(5Z)-5-[(E)-2-methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid	1646337: Inhibition of AKR1B10 (unknown origin) pretreated with 0.25M DMSO followed by compound treatment by DMSO-perturbation assay	ic50	0.0352	uM
2-phenylethyl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate	641083: Mixed-type inhibition at human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as inhibition of NADP+ linked geraniol oxidation by fluorescence analysis	ki	0.0460	uM
(1E,6E)-1,7-bis(4-hydroxyphenyl)hepta-1,6-diene-3,5-dione	1465693: Inhibition of AKR1B10 (unknown origin)	ic50	0.0600	uM
2-phenylethyl (E)-3-(4-hydroxyphenyl)prop-2-enoate	641086: Inhibition of human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as pyridine-3-aldehyde reduction by spectrometric analysis	ic50	0.0690	uM
(4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid	697012: Competitive inhibition of dehydrogenase activity of N-terminal 6His-tagged human AKR1B10 expressed in Escherichia coli BL21(DE3) assessed as NADP+-linked geraniol oxidation	ki	0.0720	uM
benzyl (E)-3-(4-hydroxyphenyl)prop-2-enoate	641086: Inhibition of human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as pyridine-3-aldehyde reduction by spectrometric analysis	ic50	0.1300	uM
trans-(3R,5R)-3,5-bis[[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy]-1,4-dihydroxycyclohexane-1-carboxylic acid	641086: Inhibition of human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as pyridine-3-aldehyde reduction by spectrometric analysis	ic50	0.1300	uM
benzyl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate	641086: Inhibition of human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as pyridine-3-aldehyde reduction by spectrometric analysis	ic50	0.2100	uM
(1S,3R,4R,5R)-3,4-bis[[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxy]-1,5-dihydroxycyclohexane-1-carboxylic acid	641086: Inhibition of human recombinant N-terminus His6-tagged AKR1B10 expressed in Escherichia coli BL21 DE3 assessed as pyridine-3-aldehyde reduction by spectrometric analysis	ic50	0.2400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	13
sodium arsenite	increases abundance, increases expression	7
Tetrachlorodibenzodioxin	increases expression	6
Tobacco Smoke Pollution	affects expression, increases expression	6
Glyceraldehyde	affects cotreatment, affects reduction, increases metabolic processing, increases reduction, decreases reaction (+1 more)	5
NADP	increases oxidation, increases reduction, decreases reduction, affects binding, increases activity (+3 more)	5
pirinixic acid	decreases activity, affects binding, increases activity, increases expression, decreases reaction (+1 more)	4
Particulate Matter	decreases expression, increases abundance, increases expression	4
sulforaphane	increases expression	3
4-hydroxy-2-nonenal	increases metabolic processing, increases reduction, decreases reaction	3
resorcinol	increases expression	3
Acrolein	affects metabolic processing, decreases response to substance, increases reduction	3
Air Pollutants	decreases expression, increases abundance, increases expression	3
Cisplatin	decreases response to substance, affects cotreatment, increases expression	3
Estradiol	affects cotreatment, decreases expression	3
Eugenol	increases expression	3
fenofibric acid	decreases reaction, increases reduction, decreases activity	2
lead acetate	increases expression	2
2-butenal	affects metabolic processing, decreases response to substance, increases reduction	2
ciprofibrate	increases reduction, decreases activity, decreases reaction	2
perfluorooctanoic acid	increases expression	2
sorbinil	increases reduction, decreases activity, decreases reaction	2
zopolrestat	increases reduction, decreases activity, decreases reaction	2
ethyl 1-benzyl-3-hydroxy-2(5H)-oxopyrrole-4-carboxylate	decreases reaction, increases reduction, decreases activity	2
U 0126	decreases expression, decreases reaction	2
4-oxo-2-nonenal	decreases reaction, decreases activity, increases metabolic processing, increases reduction	2
Acetaminophen	decreases expression	2
Aerosols	increases expression, affects expression	2
Ampicillin	decreases expression	2
Antimony Potassium Tartrate	increases expression, increases abundance	2

ChEMBL screening assays

88 unique, capped per target: 86 binding, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1174247	Binding	Inhibition of reductase activity of N-terminal 6His-tagged AKR1B10 expressed in Escherichia coli BL21(DE3) assessed as inhibition of NADPH linked pyridine-3-aldehyde reduction	Chromene-3-carboxamide derivatives discovered from virtual screening as potent inhibitors of the tumour maker, AKR1B10. — Bioorg Med Chem
CHEMBL3821395	ADMET	Binding affinity to AKR1B10 in human HepG2 assessed as intensity fold change of cumulated normalized intensity of protein between capture and competition assay at 100 uM after 1 hr in presence of inactive Tcp-CC 14 by differential competiti	Identification of Potential Off-target Toxicity Liabilities of Catechol-O-methyltransferase Inhibitors by Differential Competition Capture Compound Mass Spectrometry. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0TJ	Ubigene Hep G2 AKR1B10 KO	Cancer cell line	Male
CVCL_SC10	HAP1 AKR1B10 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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