AKR1A1

Summary

AKR1A1 (aldo-keto reductase family 1 member A1, HGNC:380) is a protein-coding gene on chromosome 1p34.1, encoding Aldo-keto reductase family 1 member A1 (P14550). 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, also known as aldehyde reductase, is involved in the reduction of biogenic and xenobiotic aldehydes and is present in virtually every tissue. Multiple alternatively spliced transcript variants of this gene exist, all encoding the same protein.

Source: NCBI Gene 10327 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 59 total
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_153326

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:380
Approved symbol	AKR1A1
Name	aldo-keto reductase family 1 member A1
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	ALR, DD3
Ensembl gene	ENSG00000117448
Ensembl biotype	protein_coding
OMIM	103830
Entrez	10327

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 32 protein_coding, 8 protein_coding_CDS_not_defined

ENST00000351829, ENST00000372070, ENST00000434299, ENST00000471651, ENST00000473038, ENST00000475919, ENST00000475985, ENST00000476957, ENST00000481885, ENST00000487654, ENST00000495913, ENST00000496999, ENST00000497973, ENST00000621846, ENST00000863936, ENST00000863937, ENST00000863938, ENST00000863939, ENST00000863940, ENST00000863941, ENST00000863942, ENST00000863943, ENST00000863944, ENST00000863945, ENST00000863946, ENST00000863947, ENST00000863948, ENST00000863949, ENST00000863950, ENST00000863951, ENST00000863952, ENST00000863953, ENST00000940609, ENST00000940610, ENST00000940611, ENST00000940612, ENST00000940613, ENST00000940614, ENST00000962573, ENST00000962574

RefSeq mRNA: 4 — MANE Select: NM_153326 NM_001202413, NM_001202414, NM_006066, NM_153326

CCDS: CCDS523

Canonical transcript exons

ENST00000351829 — 9 exons

Exon	Start	End
ENSE00003537714	45568927	45568999
ENSE00003579967	45567982	45568177
ENSE00003645396	45569891	45570049
ENSE00003653931	45568485	45568684
ENSE00003655052	45569143	45569229
ENSE00003704568	45566869	45567020
ENSE00003705768	45561789	45561878
ENSE00003708315	45566569	45566688
ENSE00003908341	45550826	45551155

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.7389 / max 450.6606, expressed in 1826 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2691	34.1457	1817
2693	24.4896	1818
2694	9.2701	1663
2692	3.8336	1353

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nephron tubule	UBERON:0001231	99.13	gold quality
kidney epithelium	UBERON:0004819	98.84	gold quality
nasal cavity epithelium	UBERON:0005384	98.83	gold quality
ileal mucosa	UBERON:0000331	98.80	gold quality
right lobe of liver	UBERON:0001114	98.78	gold quality
palpebral conjunctiva	UBERON:0001812	98.78	gold quality
adult mammalian kidney	UBERON:0000082	98.71	gold quality
body of pancreas	UBERON:0001150	98.66	gold quality
renal glomerulus	UBERON:0000074	98.55	gold quality
mucosa of transverse colon	UBERON:0004991	98.51	gold quality
parotid gland	UBERON:0001831	98.49	gold quality
metanephric glomerulus	UBERON:0004736	98.48	gold quality
duodenum	UBERON:0002114	98.45	gold quality
jejunal mucosa	UBERON:0000399	98.39	gold quality
cortex of kidney	UBERON:0001225	98.36	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.27	gold quality
esophagus mucosa	UBERON:0002469	98.25	gold quality
cortical plate	UBERON:0005343	98.25	gold quality
ganglionic eminence	UBERON:0004023	98.21	gold quality
adult organism	UBERON:0007023	98.17	gold quality
kidney	UBERON:0002113	98.13	gold quality
rectum	UBERON:0001052	98.11	gold quality
liver	UBERON:0002107	98.10	gold quality
pancreas	UBERON:0001264	98.05	gold quality
saliva-secreting gland	UBERON:0001044	98.01	gold quality
lower esophagus mucosa	UBERON:0035834	97.98	gold quality
minor salivary gland	UBERON:0001830	97.97	gold quality
adenohypophysis	UBERON:0002196	97.97	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.92	gold quality
mouth mucosa	UBERON:0003729	97.90	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	64.06
E-HCAD-10	yes	31.86
E-CURD-112	yes	5.30
E-MTAB-10042	yes	4.32
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CEBPG, GLI3, MYC, NR5A2, USF1

Literature-anchored findings (GeneRIF, showing 8)

• structure of Apo R268A human aldose reductase reveals hinges and latches that control the kinetic mechanism (PMID:15769597)
• the binding site residues deviating between ALR1 and ALR2 influence ligand affinity in a complex interplay, presumably involving changes of dynamic properties and differences of the solvation/desolvation balance upon ligand binding (PMID:18495158)
• AKR1A1 has little effect on the production of gamma-hydroxybutyrate (PMID:21276435)
• AKR1A1 could be involved in the metabolism of 4-hydroxynonenal and play a role in the resistance to oxidative stress (PMID:23643085)
• prostaglandin F synthase activity of human and bovine aldo-keto reductases (PMID:23747692)
• Data (including data from studies in knockout and transgenic mice) suggest that AKR1A1 in liver is involved in bioactivation of xenobiotic/carcinogen thioacetamide (TAA); Akr1a-/- knockout mice are resistant to TAA-induced liver injury/hepatotoxicity. (PMID:29763686)
• (5-Hydroxy-4-oxo-2-styryl-4H-pyridin-1-yl)-acetic Acid Derivatives as Multifunctional Aldose Reductase Inhibitors. (PMID:33158254)
• Mechanistic study of the Aldo-keto reductase family 1 member A1 in regulating mesenchymal stem cell fate decision toward adipogenesis and osteogenesis. (PMID:38092142)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	akr1a1b	ENSDARG00000052030
mus_musculus	Akr1a1	ENSMUSG00000028692
rattus_norvegicus	Akr1a1	ENSRNOG00000016727
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

Paralogs (16): AKR7A2 (ENSG00000053371), KCNAB2 (ENSG00000069424), AKR1B1 (ENSG00000085662), AKR1D1 (ENSG00000122787), AKR1C2 (ENSG00000151632), AKR7A3 (ENSG00000162482), AKR1E2 (ENSG00000165568), KCNAB1 (ENSG00000169282), KCNAB3 (ENSG00000170049), AKR1C1 (ENSG00000187134), AKR1C3 (ENSG00000196139), AKR1B10 (ENSG00000198074), AKR1C4 (ENSG00000198610), AKR7L (ENSG00000211454), AKR1B15 (ENSG00000227471), AKR1C8 (ENSG00000264006)

Protein

Protein identifiers

Aldo-keto reductase family 1 member A1 — P14550 (reviewed: P14550)

Alternative names: Alcohol dehydrogenase [NADP(+)], Aldehyde reductase, Glucuronate reductase, Glucuronolactone reductase, S-nitroso-CoA reductase

All UniProt accessions (5): P14550, Q5T621, V9GYG2, V9GYP9, V9HWI0

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 enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosaccharides and bile acids, with a preference for negatively charged substrates, such as glucuronate and succinic semialdehyde. Functions as a detoxifiying enzyme by reducing a range of toxic aldehydes. Reduces methylglyoxal and 3-deoxyglucosone, which are present at elevated levels under hyperglycemic conditions and are cytotoxic. Involved also in the detoxification of lipid-derived aldehydes like acrolein. Plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs, including the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN). Also acts as an inhibitor of protein S-nitrosylation by mediating degradation of S-nitroso-coenzyme A (S-nitroso-CoA), a cofactor required to S-nitrosylate proteins. S-nitroso-CoA reductase activity is involved in reprogramming intermediary metabolism in renal proximal tubules, notably by inhibiting protein S-nitrosylation of isoform 2 of PKM (PKM2). Also acts as a S-nitroso-glutathione reductase by catalyzing the NADPH-dependent reduction of S-nitrosoglutathione. Displays no reductase activity towards retinoids.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Cytosol. Apical cell membrane.

Tissue specificity. Widely expressed. Highly expressed in kidney, salivary gland and liver. Detected in trachea, stomach, brain, lung, prostate, placenta, mammary gland, small intestine and lung.

Similarity. Belongs to the aldo/keto reductase family.

RefSeq proteins (4): NP_001189342, NP_001189343, NP_006057, NP_697021* (*=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
IPR044481	AKR1A	Family

Pfam: PF00248

Enzyme classification (BRENDA):

• EC 1.1.1.2 — alcohol dehydrogenase (NADP+) (BRENDA: 93 organisms, 706 substrates, 243 inhibitors, 649 Km, 140 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
NADPH	0.001–4.11	57
NADP+	0.007–46.7	45
P-NITROBENZALDEHYDE	0.0013–5.9	34
DL-GLYCERALDEHYDE	1.3–76	27
ACETALDEHYDE	0.17–210	22
ETHANOL	0.013–600	22
D-GLUCURONATE	1.5–364	17
NADH	0.025–23.84	17
P-CARBOXYBENZALDEHYDE	0.004–4	17
NAD+	0.096–20	16
SUCCINIC SEMIALDEHYDE	0.028–18	15
3-PYRIDINECARBOXALDEHYDE	0.008–8.61	13
2-HYDROXYTETRAHYDROFURAN	0.85–6.38	10
PROPIONALDEHYDE	0.008–14.54	10
BENZALDEHYDE	0.01–9.09	9

Catalyzed reactions (Rhea), 12 shown:

• allyl alcohol + NADP(+) = acrolein + NADPH + H(+) (RHEA:12168)
• L-gulonate + NADP(+) = aldehydo-D-glucuronate + NADPH + H(+) (RHEA:14909)
• a primary alcohol + NADP(+) = an aldehyde + NADPH + H(+) (RHEA:15937)
• L-gulono-1,4-lactone + NADP(+) = D-glucurono-3,6-lactone + NADPH + H(+) (RHEA:18925)
• glycerol + NADP(+) = D-glyceraldehyde + NADPH + H(+) (RHEA:23592)
• hydroxyacetone + NADP(+) = methylglyoxal + NADPH + H(+) (RHEA:27986)
• glycerol + NADP(+) = L-glyceraldehyde + NADPH + H(+) (RHEA:38111)
• a 4-hydroxynonen-1-ol + NADP(+) = a 4-hydroxynonenal + NADPH + H(+) (RHEA:58336)
• 3-deoxyfructose + NADP(+) = 3-deoxyglucosone + NADPH + H(+) (RHEA:58668)
• pyridine 3-methanol + NADP(+) = pyridine-3-carbaldehyde + NADPH + H(+) (RHEA:58776)
• S-nitrosoglutathione + NADPH + H(+) = S-(hydroxysulfenamide)glutathione + NADP(+) (RHEA:63500)
• S-nitroso-CoA + NADPH + H(+) = sulfinamide-CoA + NADP(+) (RHEA:78375)

UniProt features (68 total): binding site 17, strand 14, helix 13, mutagenesis site 10, modified residue 7, sequence variant 2, initiator methionine 1, chain 1, active site 1, site 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2ALR	X-RAY DIFFRACTION	2.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14550-F1	96.93	0.92

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): 50 (proton donor); 80 (lowers pka of active site tyr)

Ligand- & substrate-binding residues (17): 213; 215; 216; 263; 264; 265; 266; 269; 272; 273; 11–20; 21 …

Post-translational modifications (7): 2, 4, 38, 127, 127, 145, 211

Mutagenesis-validated functional residues (10):

Position	Phenotype
50	abolished reductase activity.
50	complete loss of enzymatic activity.
80	complete loss of enzymatic activity.
113	strong decrease in enzymatic activity.
127	abolished s-nitroso-coa reductase activity without affecting ability to reduce s-nitrosoglutathione, glyceraldehyde or g
299	no change in enzymatic activity.
300	no change in enzymatic activity.
312	abolished s-nitrosoglutathione reductase activity without affecting ability to reduce s-nitroso-coa.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-156590	Glutathione conjugation
R-HSA-5661270	Formation of xylulose-5-phosphate
R-HSA-1430728	Metabolism
R-HSA-156580	Phase II - Conjugation of compounds
R-HSA-211859	Biological oxidations
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 227 (showing top): MODULE_93, REACTOME_BIOLOGICAL_OXIDATIONS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, AAGCCAT_MIR135A_MIR135B, GOBP_ALDEHYDE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_KETONE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS

GO Biological Process (9): lipid metabolic process (GO:0006629), obsolete D-glucuronate catabolic process to D-xylulose 5-phosphate (GO:0019640), negative regulation of apoptotic process (GO:0043066), daunorubicin metabolic process (GO:0044597), doxorubicin metabolic process (GO:0044598), aldehyde catabolic process (GO:0046185), cellular detoxification of aldehyde (GO:0110095), glutathione derivative biosynthetic process (GO:1901687), D-glucuronate catabolic process (GO:0042840)

GO Molecular Function (11): aldose reductase (NADPH) activity (GO:0004032), alcohol dehydrogenase (NADP+) activity (GO:0008106), allyl-alcohol dehydrogenase activity (GO:0047655), L-glucuronate reductase activity (GO:0047939), glucuronolactone reductase activity (GO:0047941), glycerol dehydrogenase (NADP+) activity (GO:0047956), S-nitrosoglutathione reductase (NADH) activity (GO:0080007), S-nitrosoglutathione reductase (NADPH) activity (GO:0160163), methylglyoxal reductase (NADPH) (acetol producing) activity (GO:1990002), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (8): obsolete extracellular space (GO:0005615), cytosol (GO:0005829), apical plasma membrane (GO:0016324), synapse (GO:0045202), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Metabolism	2
Phase II - Conjugation of compounds	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Biological oxidations	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	7
cellular anatomical structure	3
glycoside metabolic process	2
polyketide metabolic process	2
ketone metabolic process	2
primary metabolic process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
primary alcohol metabolic process	1
tertiary alcohol metabolic process	1
aldehyde metabolic process	1
catabolic process	1
cellular response to aldehyde	1
cellular detoxification	1
sulfur compound biosynthetic process	1
glucuronate catabolic process	1
alcohol dehydrogenase (NADP+) activity	1
alcohol dehydrogenase [NAD(P)+] activity	1
binding	1
catalytic activity	1
cytoplasm	1
apical part of cell	1
plasma membrane region	1
cell junction	1
extracellular vesicle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1818 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AKR1A1	CBR3	O75828	912
AKR1A1	CBR1	P16152	893
AKR1A1	MIOX	Q9UGB7	837
AKR1A1	AKR7A2	O43488	780
AKR1A1	ADM2	Q7Z4H4	761
AKR1A1	DHRS9	Q9BPW9	724
AKR1A1	MAPK8IP2	Q13387	649
AKR1A1	PARVB	Q9HBI1	649
AKR1A1	AKR7A3	O95154	604
AKR1A1	ALDH3A2	P51648	511
AKR1A1	ADH6	P28332	507
AKR1A1	ADH5	P11766	480
AKR1A1	DHDH	Q9UQ10	464
AKR1A1	SORD	Q00796	443
AKR1A1	MAOB	P27338	434

IntAct

42 interactions, top by confidence:

A	B	Type	Score
AKR1A1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
AKR1A1	HTT	psi-mi:“MI:0915”(physical association)	0.560
TERF2IP	AKR1A1	psi-mi:“MI:0915”(physical association)	0.510
AKR1A1	IGHG2	psi-mi:“MI:0915”(physical association)	0.400
AKR1A1	PRKAA1	psi-mi:“MI:0915”(physical association)	0.400
SLC16A4	AKR1A1	psi-mi:“MI:0915”(physical association)	0.400
AKR1A1	TERF1	psi-mi:“MI:0915”(physical association)	0.370
AKR1A1	HTR6	psi-mi:“MI:0915”(physical association)	0.370
AKR1A1	E7	psi-mi:“MI:0915”(physical association)	0.370
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
CAV1	PPM1G	psi-mi:“MI:0914”(association)	0.350
SH3BGRL	MYO1C	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
rep	EIF5B	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SAR1B	UBA6	psi-mi:“MI:0914”(association)	0.350
PBK	LGALS9	psi-mi:“MI:0914”(association)	0.350
SLC25A32	AKR1A1	psi-mi:“MI:0914”(association)	0.350
AKR1A1	AKR1B1	psi-mi:“MI:0914”(association)	0.350
AKR1A1	POTEF	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350
VCP	FAM171A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (78): IGHG2 (Affinity Capture-MS), AKR1A1 (Co-fractionation), AKR1A1 (Co-fractionation), AKR1A1 (Co-fractionation), AKR1A1 (Co-fractionation), AKR1A1 (Co-fractionation), AKR1A1 (Co-fractionation), AKR1A1 (Co-fractionation), AKR1A1 (Co-fractionation), AKR1A1 (Co-fractionation), AKR1A1 (Co-fractionation), AKR1A1 (Co-fractionation), AKR1A1 (Co-fractionation), AKR1A1 (Co-fractionation), AKR1A1 (Co-fractionation)

ESM2 similar proteins: A0A1D5XGW0, A0A1X9QHJ0, A0A2P1GIY9, A0A9E7S518, A0A9E7S5B9, A1CRI1, A1D4E3, A2Q8B5, B0XNR0, B4F9A4, B8N195, B9VRJ2, C5FFQ7, E7C196, G4MZI3, G4N708, O49133, O70473, O80944, P0DXG9, P0DXH7, P14550, P23901, P26690, P28475, P38715, P50578, P51635, Q00727, Q0PCF4, Q10PE7, Q2UKD0, Q3ZCJ2, Q4WJT9, Q5BGA7, Q5R5D5, Q5ZK84, Q6AZW2, Q7G764, Q7G765

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1378 predictions. Top by Δscore:

Variant	Effect	Δscore
1:45564238:GAGC:G	donor_gain	1.0000
1:45564241:C:G	donor_gain	1.0000
1:45566685:C:T	donor_gain	1.0000
1:45566686:AAGG:A	donor_loss	1.0000
1:45566687:AGG:A	donor_loss	1.0000
1:45566688:GGTAA:G	donor_loss	1.0000
1:45566689:G:GA	donor_loss	1.0000
1:45566690:T:G	donor_loss	1.0000
1:45566863:CACTA:C	acceptor_loss	1.0000
1:45566864:A:AG	acceptor_gain	1.0000
1:45566864:ACTAG:A	acceptor_gain	1.0000
1:45566865:C:G	acceptor_gain	1.0000
1:45566865:CTA:C	acceptor_loss	1.0000
1:45566866:TAG:T	acceptor_loss	1.0000
1:45566867:A:AG	acceptor_gain	1.0000
1:45566867:AGGC:A	acceptor_gain	1.0000
1:45566868:G:A	acceptor_loss	1.0000
1:45566868:G:GG	acceptor_gain	1.0000
1:45566868:GGC:G	acceptor_gain	1.0000
1:45566868:GGCG:G	acceptor_gain	1.0000
1:45566976:G:GT	donor_gain	1.0000
1:45566979:G:GG	donor_gain	1.0000
1:45567006:GCCT:G	donor_gain	1.0000
1:45567013:GCCTT:G	donor_gain	1.0000
1:45567016:TTTGA:T	donor_gain	1.0000
1:45567017:T:G	donor_gain	1.0000
1:45567017:T:TG	donor_gain	1.0000
1:45567019:GA:G	donor_gain	1.0000
1:45567020:AGTG:A	donor_loss	1.0000
1:45567021:G:GG	donor_gain	1.0000

AlphaMissense

2111 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:45566904:G:C	K80N	0.993
1:45566904:G:T	K80N	0.993
1:45566908:T:A	W82R	0.992
1:45566908:T:C	W82R	0.992
1:45568114:C:A	N163K	0.992
1:45568114:C:G	N163K	0.992
1:45566619:T:A	D45E	0.991
1:45566619:T:G	D45E	0.991
1:45568055:T:A	W144R	0.990
1:45568055:T:C	W144R	0.990
1:45569208:A:C	R297S	0.990
1:45569208:A:T	R297S	0.990
1:45568964:A:C	S264R	0.989
1:45568966:T:A	S264R	0.989
1:45568966:T:G	S264R	0.989
1:45569939:T:C	F321L	0.989
1:45569941:T:A	F321L	0.989
1:45569941:T:G	F321L	0.989
1:45568115:T:C	F164L	0.988
1:45568117:C:A	F164L	0.988
1:45568117:C:G	F164L	0.988
1:45568928:T:A	W252R	0.988
1:45568928:T:C	W252R	0.988
1:45568962:A:T	K263I	0.988
1:45566618:A:T	D45V	0.987
1:45566890:T:C	F76L	0.987
1:45566892:T:A	F76L	0.987
1:45566892:T:G	F76L	0.987
1:45566900:C:T	S79F	0.987
1:45568573:G:A	G214D	0.987

dbSNP variants (sampled 300 via entrez): RS1000042735 (1:45567730 G>A), RS1000104279 (1:45566449 C>T), RS1000185295 (1:45561221 G>A,C), RS1000189368 (1:45551675 C>T), RS1000521210 (1:45562725 G>A), RS1000598772 (1:45569598 G>A), RS1000838232 (1:45550205 T>C), RS1000859357 (1:45559392 G>A,C), RS1000952122 (1:45549842 C>G), RS1001354496 (1:45568826 G>A), RS1001673388 (1:45548981 G>A), RS1001935117 (1:45563395 G>A), RS1001986752 (1:45561940 C>A,G), RS1002040268 (1:45556644 C>T), RS1002071076 (1:45550520 G>T)

Disease associations

OMIM: gene MIM:103830 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): developmental and epileptic encephalopathy (MONDO:0100620)

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST004611_106	High light scatter reticulocyte count	4.000000e-12
GCST005951_37	Body mass index	8.000000e-10
GCST006585_1094	Blood protein levels	9.000000e-175
GCST006629_48	Pulse pressure	7.000000e-14
GCST007269_22	Pulse pressure	2.000000e-09
GCST008058_157	Estimated glomerular filtration rate	4.000000e-14
GCST008059_92	Estimated glomerular filtration rate	3.000000e-19
GCST010696_7	Cortical thickness (min-P)	3.000000e-08
GCST010697_28	Cortical surface area (min-P)	2.000000e-08
GCST010698_30	Subcortical volume (min-P)	3.000000e-08
GCST010699_45	Brain morphology (min-P)	3.000000e-08
GCST010700_23	Cortical thickness (MOSTest)	1.000000e-10
GCST010701_9	Cortical surface area (MOSTest)	2.000000e-08
GCST010702_139	Subcortical volume (MOSTest)	4.000000e-14
GCST010703_258	Brain morphology (MOSTest)	2.000000e-13
GCST90002385_611	High light scatter reticulocyte count	1.000000e-19
GCST90002406_141	Reticulocyte fraction of red cells	6.000000e-17

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0004340	body mass index
EFO:0005763	pulse pressure measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2246 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 83,252 (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
CHEMBL109	VALPROIC ACID	4	65,937
CHEMBL436	TOLRESTAT	4	3,768
CHEMBL56337	EPALRESTAT	4	110
CHEMBL266497	SORBINIL	3	2,026
CHEMBL10372	ZOPOLRESTAT	2	3,266
CHEMBL10413	ZENARESTAT	2	2,803
CHEMBL269455	IMIRESTAT	2	890
CHEMBL273910	MINALRESTAT	2	1,586
CHEMBL363387	LIDORESTAT	2	192
CHEMBL84446	FIDARESTAT	2	2,674

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6690497	AKR1A1		0.00	0
rs2229540	AKR1A1		0.00	0

Binding affinities (BindingDB)

40 measured of 40 human assays (40 total across all organisms); most potent 40 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
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
2-{3-[(6-chloro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	2100 nM
2-{6-chloro-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	2700 nM
2-(6-bromo-3-{[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl}-1H-indol-1-yl)acetic acid	IC50	3400 nM
2-{3-[(6-fluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	4500 nM
2-{5-bromo-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	4700 nM
2-[5-(benzyloxy)-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl]acetic acid	IC50	4800 nM
2-(5-chloro-3-{[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl}-1H-indol-1-yl)acetic acid	IC50	4900 nM
2-{3-[(4,6-difluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	5100 nM
2-(3-{[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl}-1H-indol-1-yl)acetic acid	IC50	5600 nM
2-{6-phenyl-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	6100 nM
2-{3-[(5-fluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	6400 nM
2-{3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}propanoic acid	IC50	6500 nM
2-{7-fluoro-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	7000 nM
2-{6-fluoro-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	7500 nM
FR 74366	IC50	9900 nM
2-{5-phenyl-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	10000 nM
2-(5-methyl-3-{[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl}-1H-indol-1-yl)acetic acid	IC50	10200 nM
2-{3-[(4-fluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	11000 nM
2-{5-chloro-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	11000 nM
2-{5-phenoxy-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	11000 nM
2-{3-[2-(4,5,7-trifluoro-1,3-benzothiazol-2-yl)ethyl]-1H-indol-1-yl}acetic acid	IC50	11000 nM
2-{6-methoxy-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	12000 nM
2-{3-[(5,6-difluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	13000 nM
2-{2-methyl-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	13000 nM
2-{6-methyl-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	13000 nM
2-{4-chloro-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	14000 nM
2-{2-phenyl-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	16000 nM
2-{3-[(7-fluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	18000 nM
2-{7-bromo-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	18000 nM
2-{7-chloro-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	19000 nM
2-{5-fluoro-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	21000 nM
2-{5-methoxy-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	21000 nM
2-{7-methyl-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	21000 nM
Indoleacetic Acid Inhibitor 9	IC50	27000 nM
2-{5-methyl-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}acetic acid	IC50	34000 nM
2-[5-(morpholin-4-yl)-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl]acetic acid	IC50	41000 nM
2-[6-(morpholin-4-yl)-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl]acetic acid	IC50	44000 nM
3-{3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]-1H-indol-1-yl}propanoic acid	IC50	88000 nM

ChEMBL bioactivities

60 potent at pChembl≥5 of 96 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.17	IC50	6.7	nM	MINALRESTAT
7.60	IC50	25	nM	CHEMBL5397238
7.54	IC50	29	nM	CHEMBL5431713
7.48	IC50	33	nM	CHEMBL5396251
7.38	IC50	42	nM	CHEMBL5400944
7.35	IC50	45	nM	IMIRESTAT
7.32	IC50	48	nM	CHEMBL5397238
7.29	IC50	51	nM	CHEMBL5417323
7.28	IC50	53	nM	CHEMBL5438141
7.24	IC50	57	nM	CHEMBL5431549
7.24	IC50	57	nM	IMIRESTAT
7.23	IC50	59	nM	CHEMBL5414200
7.20	IC50	63	nM	CHEMBL5399554
7.19	IC50	65	nM	TOLRESTAT
7.18	IC50	66	nM	CHEMBL5418720
7.17	IC50	67	nM	CHEMBL5400147
7.17	IC50	68	nM	CHEMBL5414059
7.17	IC50	67	nM	CHEMBL5396251
7.14	IC50	72	nM	CHEMBL5400501
7.13	IC50	74	nM	CHEMBL5421140
7.10	IC50	80	nM	CHEMBL5413369
7.09	IC50	82	nM	CHEMBL5397588
7.09	IC50	82	nM	CHEMBL5399554
7.03	IC50	93	nM	CHEMBL5483061
6.91	IC50	122	nM	CHEMBL5423635
6.90	IC50	127	nM	CHEMBL5420064
6.49	IC50	325	nM	EPALRESTAT
6.14	IC50	720	nM	TOLRESTAT
5.92	IC50	1200	nM	FIDARESTAT
5.92	IC50	1200	nM	SORBINIL
5.82	IC50	1500	nM	CHEMBL4081954
5.77	IC50	1700	nM	CHEMBL4089817
5.71	IC50	1940	nM	TOLRESTAT
5.68	IC50	2100	nM	CHEMBL192213
5.58	IC50	2600	nM	EPALRESTAT
5.57	IC50	2700	nM	CHEMBL371162
5.57	IC50	2700	nM	ZOPOLRESTAT
5.47	IC50	3400	nM	CHEMBL191570
5.35	IC50	4500	nM	CHEMBL193570
5.34	IC50	4600	nM	SORBINIL
5.33	IC50	4700	nM	CHEMBL192434
5.33	IC50	4700	nM	CHEMBL1944858
5.32	IC50	4800	nM	CHEMBL192399
5.31	IC50	4900	nM	CHEMBL371122
5.29	IC50	5100	nM	CHEMBL192534
5.27	IC50	5400	nM	SORBINIL
5.25	IC50	5600	nM	CHEMBL410917
5.21	IC50	6100	nM	CHEMBL195065
5.19	IC50	6400	nM	CHEMBL193569
5.19	IC50	6500	nM	CHEMBL193307

PubChem BioAssay actives

76 with measured affinity, of 166 total; 47 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-[(4-bromo-2-fluorophenyl)methyl]-6-fluorospiro[isoquinoline-4,3’-pyrrolidine]-1,2’,3,5’-tetrone	489639: Inhibition of N-terminal 6His-tagged human aldehyde reductase expressed in Escherichia coli BL21(DE3) mediated D-glucuronate reduction	ic50	0.0067	uM
2-(2,7-difluoro-3-hydroxy-2’,5’-dioxospiro[fluorene-9,4’-imidazolidine]-4-yl)acetic acid	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0250	uM
2,7-difluoro-3-(oxetan-3-yloxy)spiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0290	uM
2-cyclobutyl-7-fluorospiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0330	uM
2-(7-fluoro-2’,5’-dioxospiro[fluorene-9,4’-imidazolidine]-3-yl)oxyacetic acid	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0420	uM
2,7-difluorospiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987576: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using DL-glyceraldehyde as substrate	ic50	0.0450	uM
2-bromo-7-fluorospiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0510	uM
2-chlorospiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0530	uM
2-(2,7-difluoro-2’,5’-dioxospiro[fluorene-9,4’-imidazolidine]-4-yl)acetic acid	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0570	uM
4-[2-(azetidin-1-yl)-2-oxoethoxy]-2,7-difluorospiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0590	uM
2-(2,7-difluoro-2’,5’-dioxospiro[fluorene-9,4’-imidazolidine]-3-yl)oxyacetic acid	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0630	uM
2-[[6-methoxy-5-(trifluoromethyl)naphthalene-1-carbothioyl]-methylamino]acetic acid	1987576: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using DL-glyceraldehyde as substrate	ic50	0.0650	uM
4-(1-cyclopentyltriazol-4-yl)-2,7-difluorospiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0660	uM
2,5-difluorospiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0670	uM
2-fluoro-6-methoxyspiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0680	uM
3-cyclopropyl-2,7-difluorospiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0720	uM
2-fluoro-6-(2-hydroxyethoxy)spiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0740	uM
6-[2-(azetidin-1-yl)-2-oxoethoxy]-2-fluorospiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0800	uM
4-fluorospiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0820	uM
2-cyclopropylspiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.0930	uM
2-cyclopropyl-7-fluorospiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.1220	uM
2,7-dichlorospiro[fluorene-9,5’-imidazolidine]-2’,4’-dione	1987577: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using SNO-CoA as substrate incubated for 2 mins in presence of NADPH	ic50	0.1270	uM
2-[(5Z)-5-[(E)-2-methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]acetic acid	1987576: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using DL-glyceraldehyde as substrate	ic50	0.3250	uM
(2S,4S)-6-fluoro-2’,5’-dioxospiro[2,3-dihydrochromene-4,4’-imidazolidine]-2-carboxamide	242590: Inhibitory concentration against human ALR1 Aldehyde reductase using DL-glyceraldehyde	ic50	1.2000	uM
(4S)-6-fluorospiro[2,3-dihydrochromene-4,5’-imidazolidine]-2’,4’-dione	1987576: Inhibition of C-terminal 6His-tagged human recombinant SCoR2 AKR1A1 expressed in Escherichia coli BL21-CodonPlus competent cells using DL-glyceraldehyde as substrate	ic50	1.2000	uM
7-hydroxy-N-[3-(4-hydroxyphenyl)propyl]-2-oxochromene-3-carboxamide	1465662: Inhibition of recombinant human AKR1A1 using pyridine-3-aldehyde as substrate	ic50	1.5000	uM
N-[3-(4-fluorophenyl)propyl]-7-hydroxy-2-oxochromene-3-carboxamide	1465662: Inhibition of recombinant human AKR1A1 using pyridine-3-aldehyde as substrate	ic50	1.7000	uM
2-[3-[(6-chloro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	2.1000	uM
2-[4-oxo-3-[[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl]phthalazin-1-yl]acetic acid	489639: Inhibition of N-terminal 6His-tagged human aldehyde reductase expressed in Escherichia coli BL21(DE3) mediated D-glucuronate reduction	ic50	2.7000	uM
2-[6-chloro-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	2.7000	uM
2-[6-bromo-3-[[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl]indol-1-yl]acetic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	3.4000	uM
2-[3-[(6-fluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	4.5000	uM
2-[5-bromo-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	4.7000	uM
2-(2-benzyl-5,7-difluoro-1-sulfanylidene-3,4-dihydropyrido[3,4-b]indol-9-yl)acetic acid	643314: Inhibition of human recombinant AKR1A1 expressed in Escherichia coli BL21 cells using D-glucuronate as substrate by spectrophotometry	ic50	4.7000	uM
2-[5-phenylmethoxy-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	4.8000	uM
2-[5-chloro-3-[[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl]indol-1-yl]acetic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	4.9000	uM
2-[3-[(4,6-difluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	5.1000	uM
2-[3-[[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl]indol-1-yl]acetic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	5.6000	uM
2-[6-phenyl-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	6.1000	uM
2-[3-[(5-fluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	6.4000	uM
2-[3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]propanoic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	6.5000	uM
2-[7-fluoro-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	7.0000	uM
2-[6-fluoro-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	7.5000	uM
2-(2-benzyl-1-sulfanylidene-3,4-dihydropyrido[3,4-b]indol-9-yl)acetic acid	643314: Inhibition of human recombinant AKR1A1 expressed in Escherichia coli BL21 cells using D-glucuronate as substrate by spectrophotometry	ic50	9.5000	uM
2-[3-[(4-bromo-2-fluorophenyl)methyl]-7-chloro-2,4-dioxoquinazolin-1-yl]acetic acid	1797506: Enzyme Inhibition Assay from Article 10.1021/jm0492094: “Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.”	ic50	9.9000	uM
2-(2-benzyl-5,7-dichloro-1-sulfanylidene-3,4-dihydropyrido[3,4-b]indol-9-yl)acetic acid	643314: Inhibition of human recombinant AKR1A1 expressed in Escherichia coli BL21 cells using D-glucuronate as substrate by spectrophotometry	ic50	10.0000	uM
2-[5-phenyl-3-[(4,5,7-trifluoro-1,3-benzothiazol-2-yl)methyl]indol-1-yl]acetic acid	242605: In vitro inhibition of recombinant human aldehyde reductase	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
benzo(a)pyrene-7,8-dione	increases reduction, increases chemical synthesis, increases expression, increases reaction, affects chemical synthesis (+2 more)	4
benzo(a)pyrene 7,8-dihydrodiol	increases activity, affects cotreatment, decreases response to substance, increases reaction, affects metabolic processing (+3 more)	3
Cadmium Chloride	increases abundance, increases expression, decreases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
bisphenol A	decreases expression, increases expression	2
succinic semialdehyde	increases reduction	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Daunorubicin	increases chemical synthesis, affects metabolic processing, increases reduction, increases metabolic processing	2
Doxorubicin	increases reduction, increases metabolic processing, increases chemical synthesis, affects metabolic processing	2
NADP	increases oxidation, increases reduction, affects metabolic processing, increases activity, increases reaction (+2 more)	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	affects cotreatment, increases expression, affects expression	2
beta-Naphthoflavone	increases expression	2
aristolochic acid I	increases expression	1
daunorubicinol	increases chemical synthesis, increases metabolic processing	1
16-ketoestrone	increases reduction	1
9,10-phenanthrenequinone	affects activity, increases reduction	1
glycidyl methacrylate	decreases expression	1
sodium arsenate	decreases expression	1
adriamycinol	increases chemical synthesis, increases metabolic processing	1
pyrogallol 1,3-dimethyl ether	affects localization, decreases expression, affects cotreatment	1
sodium bichromate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
benzo(a)pyrene-3,6-quinone	affects activity, increases reduction	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ochratoxin A	decreases expression	1
4-hydroxy-2-nonenal	increases reduction	1
4-nitrobenzaldehyde	increases reduction	1
benzo(a)pyrene-1,6-quinone	affects activity, increases reduction	1

ChEMBL screening assays

26 unique, capped per target: 25 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1174255	Binding	Inhibition of N-terminal 6His-tagged human aldehyde reductase expressed in Escherichia coli BL21(DE3) mediated D-glucuronate reduction	Chromene-3-carboxamide derivatives discovered from virtual screening as potent inhibitors of the tumour maker, AKR1B10. — Bioorg Med Chem
CHEMBL4668532	ADMET	Inhibition of N-terminal His-tagged human AKR1A1 expressed in Escherichia coli BL21 (Condon Plus) competent cells using D,L-glyceraldehyde as substrate in presence of NADPH by fluorescence method	Overview of AKR1C3: Inhibitor Achievements and Disease Insights. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2RE	Abcam HEK293T AKR1A1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT04727970	PHASE1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT03876444	PHASE2/PHASE3	UNKNOWN	Intravenous Methylprednisolone Versus Oral Prednisolone for Infantile Spasms
NCT05279118	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome
NCT05364021	PHASE1/PHASE2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	PHASE1/PHASE2	SUSPENDED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT04302116	Not specified	RECRUITING	Vigabatrin With High Dose Prednisolone Combination Therapy vs Vigabatrin Alone for Infantile Spasm
NCT05538936	Not specified	COMPLETED	The Effect of Spa and Massage on Babies on Colic Symptoms
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06266234	Not specified	RECRUITING	Characterization by Automated System on Infantile Spasmes
NCT06380192	Not specified	RECRUITING	Developmental and Epileptic Encephalopathy of Genetic Etiology: Natural History Through Reuse of Clinical Data
NCT07396883	Not specified	NOT_YET_RECRUITING	Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing
NCT07413211	Not specified	RECRUITING	Genetic Developmental and Epileptic Encephalopathy Natural History Study for Clinical Trial Readiness
NCT07531511	Not specified	NOT_YET_RECRUITING	SLC6A1-NDD Prospective Longitudinal Natural History Study
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).