AKR1C1

Summary

AKR1C1 (aldo-keto reductase family 1 member C1, HGNC:384) is a protein-coding gene on chromosome 10p15.1, encoding Aldo-keto reductase family 1 member C1 (Q04828). Cytosolic aldo-keto reductase that catalyzes NADPH-dependent reduction of ketosteroids to hydroxysteroids.

This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reaction of progesterone to the inactive form 20-alpha-hydroxy-progesterone. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14.

Source: NCBI Gene 1645 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 72 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 9 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001353

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:384
Approved symbol	AKR1C1
Name	aldo-keto reductase family 1 member C1
Location	10p15.1
Locus type	gene with protein product
Status	Approved
Aliases	DDH, MBAB, DD1, HAKRC
Ensembl gene	ENSG00000187134
Ensembl biotype	protein_coding
OMIM	600449
Entrez	1645

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000380859, ENST00000380872, ENST00000442997, ENST00000476100, ENST00000477661, ENST00000859340, ENST00000859341, ENST00000859342, ENST00000859343, ENST00000970520, ENST00000970521

RefSeq mRNA: 1 — MANE Select: NM_001353 NM_001353

CCDS: CCDS7061

Canonical transcript exons

ENST00000380872 — 9 exons

Exon	Start	End
ENSE00001605320	4966927	4967043
ENSE00001782597	4968309	4968386
ENSE00001822803	4977700	4983283
ENSE00003513221	4963415	4963528
ENSE00003526498	4972201	4972310
ENSE00003569806	4975851	4975933
ENSE00003624441	4968822	4968944
ENSE00003646345	4965914	4966081
ENSE00003654214	4972584	4972749

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 99.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 78.5048 / max 5058.4078, expressed in 1271 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103611	77.7004	1246
103609	0.6495	405
103610	0.1549	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	99.31	gold quality
mucosa of stomach	UBERON:0001199	98.84	gold quality
right lobe of liver	UBERON:0001114	98.68	gold quality
right atrium auricular region	UBERON:0006631	97.69	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.28	gold quality
body of stomach	UBERON:0001161	97.23	gold quality
metanephros cortex	UBERON:0010533	97.22	gold quality
left coronary artery	UBERON:0001626	96.84	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.66	gold quality
cardiac atrium	UBERON:0002081	96.57	gold quality
ascending aorta	UBERON:0001496	96.55	gold quality
thoracic aorta	UBERON:0001515	96.49	gold quality
descending thoracic aorta	UBERON:0002345	96.25	gold quality
gall bladder	UBERON:0002110	96.03	gold quality
right lobe of thyroid gland	UBERON:0001119	95.76	gold quality
esophagus mucosa	UBERON:0002469	95.55	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.53	gold quality
tibial nerve	UBERON:0001323	95.52	gold quality
lower esophagus	UBERON:0013473	95.52	gold quality
esophagus	UBERON:0001043	95.39	gold quality
omental fat pad	UBERON:0010414	95.33	gold quality
peritoneum	UBERON:0002358	95.24	gold quality
minor salivary gland	UBERON:0001830	95.15	gold quality
apex of heart	UBERON:0002098	94.64	gold quality
gastrocnemius	UBERON:0001388	94.42	gold quality
lower esophagus mucosa	UBERON:0035834	94.27	gold quality
left lobe of thyroid gland	UBERON:0001120	94.26	gold quality
coronary artery	UBERON:0001621	94.05	gold quality
cortical plate	UBERON:0005343	94.00	gold quality
aorta	UBERON:0000947	93.78	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	3962.29
E-MTAB-6653	yes	2551.75
E-MTAB-10553	yes	31.34
E-MTAB-5061	yes	18.78
E-GEOD-93593	yes	11.76
E-HCAD-9	yes	8.26
E-GEOD-130148	yes	4.57
E-GEOD-83139	no	2.73
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, GLI2, NFE2L2, NFYA, STAT5B, SUPT20H

miRNA regulators (miRDB)

15 targeting AKR1C1, 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-3646	100.00	73.56	5283
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-1226-3P	97.51	66.32	1063

Literature-anchored findings (GeneRIF, showing 40)

• Expression of dihydrodiol dehydrogenase in the resected stage I non-small cell lung cancer (PMID:11956619)
• Reduction of dihydrodiol dehydrogenase expression is associated with resected hepatocellular carcinoma (PMID:12579257)
• progesterone itself contributes to the regulation of local progesterone concentration through 20alpha-HSD levels in endometrial stromal cells at peri-implantation periods. (PMID:12733716)
• X ray diffraction and site-directed mutagenesis: identification of an alternative binding site for C21-steroids (PMID:12899831)
• Glaucomatous optic nerve head astrocytes express a higher level of 3 alpha-HSD isoform AKR1C1 and its mRNA than normal astrocytes. (PMID:13678667)
• Expression of SRD5A1 (5alphaR1) and SRD5A2 (5alphaR2) is elevated, and expression of AKR1C1 (20alpha-HSO), AKR1C2 (3alpha-HSO3) and AKR1C3 (3alpha-HSO2) is reduced in tumorous as compared to normal breast tissue. (PMID:15212687)
• Loss of AKR1C1 and AKR1C2 in breast cancer results in decreased progesterone catabolism, which, in combination with increased PR expression, may augment progesterone signaling by its nuclear receptors. (PMID:15492289)
• mRNA abundance and activity of AKR1C enzymes in abdominal adipose tissue are positive correlates of adiposity in women. Increased progesterone and/or dihydrotestosterone reduction in abdominal adipose tissue may impact fat cell metabolism. (PMID:15494612)
• The expression of AKR1C1 and AKR1C3 in endometrial cancer will govern the ratio of P:E2. (PMID:16338060)
• DDH may play important roles in tumor progression of squamous cell carcinoma via induction of apoptosis- and drug-resistance (PMID:16361083)
• Activity of AKR1C1 in overall oracin reduction was one order of magnitude higher compared to AKR1C2 and 1C4. (PMID:17618725)
• Carbonyl reductase-1 (CBR1), microsomal prostaglandin E synthase-1 and 2 (mPGES-1, mPGES-2), cytosolic prostaglandin E synthase (cPGES), aldoketoreductase (AKR1C1) and prostaglandin F synthase (AKR1C3) were all expressed in hair follicles. (PMID:17697149)
• Overexpression of AKR1C1 counteracted the S-phase accumulation of cells and apoptosis caused by MTX treatment. This suggests a role of AKR1C1 in cell proliferation. (PMID:17945194)
• Incubations of normal human bronchial epithelial cells with individual heavy metals showed that the upregulation of AKR1C1 and AKR1C2 was predominantly caused by lead. (PMID:18654764)
• Induction of preadipocyte differentiation increased expression levels of AKR1C1 and modified the pattern of progesterone metabolism substantially, leaving 20alpha-hydroxyprogesterone as the main metabolite generated. (PMID:18984031)
• human AKR1C enzymes (AKR1C1-4) are able to reduce conjugated steroids such as Dht-17beta-glucuronide (DhtG), Dht-17beta-sulfate (DhtS), and Tib-17beta-sulfate (TibS) (PMID:19218247)
• AKR1C subfamily genes are stress-inducible and might function as survival factors in keratinocytes. (PMID:19320734)
• AKR1C isoforms as a novel target of jasmonates in cancer cells. (PMID:19487289)
• Human AKR1C enzymatic activity plays crucial roles on induction of neoplastic transformation of mouse NIH3T3 cells. (PMID:19696165)
• non-stereo-selective cytosolic human brain tissue 3-ketosteroid reductase is refractory to inhibition by AKR1C inhibitors (PMID:20673851)
• Functionally expressed human AKR1C1 (20alpha-hydroxysteroid dehydrogenase) in the fission yeast Schizosaccharomyces pombe and demonstrate the ability of the resulting yeast strain to efficiently catalyze the reduction of progesterone or dydrogesterone. (PMID:20727920)
• analysis of single nucleotide polymorphisms of AKR1C1 and AKR1C2 (PMID:21217827)
• enhanced metabolism of progesterone by SRD5A1 and the 20alpha-HSD and 3alpha/beta-HSD activities of AKR1C1, AKR1C2 and AKR1C3 (PMID:21232532)
• role of AKR1C1in the metabolism of testosterone and progesterone via the 5beta-reductase pathway. (PMID:21521174)
• Data suggest that interleukin-1beta facilitates progesterone metabolism in cervical fibroblasts by regulating expression of AKR1C1 and AKR1C2. (PMID:22064385)
• It was concluded that the truncated E6 protein of human papillomavirus 16, known as E6*I, has a novel function in upregulating expression of human AKR1C. (PMID:22278827)
• The involvement of up-regulated AKR1C1, AKR1C3 and proteasome in CDDP resistance of colon cancers. (PMID:23165153)
• Which promoted significant reduction of AKR1C1 and AKR1C2 expression. (PMID:23183084)
• activation of the Nrf2/AKR1C axis may contribute to oxaliplatin resistance in gastric carcinoma (PMID:23933386)
• Studies indicate that mutations in aldo-keto reductase family 1 (AKR1) enzymes AKR1C1 and AKR1C4 are responsible for sexual development dysgenesis and mutations in AKR1D1 are causative in bile-acid deficiency. (PMID:24189185)
• results suggest a gender-specific modulatory effect of AKR1C1 on anxiety levels, most likely through changes in progesterone and allopregnanolone levels within and outside the brain (PMID:24390875)
• Activation of AKR1C1/ERbeta induces apoptosis by downregulation of c-FLIP in prostate cancer cells. (PMID:25816367)
• Data show that increased levels of AKR1C1/C2 enhanced the sensitivity of esophageal squamous cell carcinoma (ESCC) cells to ethyl-3,4-dihydroxybenzoate (EDHB). (PMID:26934124)
• Decreased invasion caused by AKR1C1 knockdown suggests a novel role of AKR1C1 in cancer invasion, which is probably due to the regulation of Rac1, Src, or Akt. An inflammatory cytokine, interleukin-1beta, was found to increase AKR1C1 in bladder cancer cell lines. (PMID:27698389)
• the present study suggests that AKR1C1, AKR1C2, AKR1C3, and AKR1C4 are closely associated with drug resistance to both CDDP and 5FU, and that mefenamic acid, an inhibitor of AKR1C, restores sensitivity through inhibition of drug-resistance in human cancer cells. (PMID:28259989)
• AKR1C1 activates STAT3 pathway to promote NSCLC metastasis. (PMID:29344298)
• OPSCC with integrated HPV16 show upregulation of AKR1C1 and AKR1C3 expression. (PMID:30367463)
• AKR1C1 is a crucial regulator for cisplatin-resistance in HNSCC and also poor prognostic marker for patients. Targeting the AKR1C1-STAT axis may provide a new therapeutic strategy to treat patients who are refractory to cisplatin treatment. (PMID:31182137)
• Aldo-keto reductases protect metastatic melanoma from ER stress-independent ferroptosis. (PMID:31780644)
• Human dehydrogenase/reductase SDR family member 11 (DHRS11) and aldo-keto reductase 1C isoforms in comparison: Substrate and reaction specificity in the reduction of 11-keto-C19-steroids. (PMID:31926269)

Cross-species orthologs

18 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
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), AKR1C3 (ENSG00000196139), AKR1B10 (ENSG00000198074), AKR1C4 (ENSG00000198610), AKR7L (ENSG00000211454), AKR1B15 (ENSG00000227471), AKR1C8 (ENSG00000264006)

Protein

Protein identifiers

Aldo-keto reductase family 1 member C1 — Q04828 (reviewed: Q04828)

Alternative names: 20alpha-hydroxysteroid dehydrogenase, 3beta-hydroxysteroid 3-dehydrogenase, Chlordecone reductase homolog HAKRC, Dihydrodiol dehydrogenase 1, High-affinity hepatic bile acid-binding protein

All UniProt accessions (3): A6NHU4, Q04828, H0Y804

UniProt curated annotations — full annotation on UniProt →

Function. Cytosolic aldo-keto reductase that catalyzes NADPH-dependent reduction of ketosteroids to hydroxysteroids. Displays broad substrate specificity with distinct positional and stereochemistry, primarily generating 20alpha-hydroxysteroids, but also 3alpha/beta- and 17beta-hydroxysteroids. Involved in neurosteroid metabolism. Reduces 5alpha-dihydrodeoxycorticosterone (5-alpha-DHDOC) to neuroactive steroid 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC) known to alter neural excitability via allosteric activation of gamma-aminobutyric acid type A (GABAAR) receptors. Inactivates 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) into less potent neurosteroid 3alpha,20alpha-dihydroxy-5alpha-pregnane. Catalyzes the reduction of progesterone to less potent progestogen (20S)-hydroxypregn-4-en-3-one likely regulating ligand availability for progesterone receptors. In androgen catabolism, may predominantly act as a phase I enzyme by introducing a hydroxyl group prior to conjugation. It can nevertheless participate in the alternative phase II pathway by directly reducing sulfate- or glucuronide-conjugated androgens. In vitro can efficiently catalyze bidirectional conversion between ketosteroids and hydroxysteroids using NADPH/NADP(+) or NADH/NAD(+) as cofactors. In vivo however, the reductase activity prevails since the major reducing cofactor NADPH inhibits NAD(+)-dependent oxidase activity.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Expressed in all tissues tested including liver, prostate, testis, adrenal gland, brain, uterus, mammary gland and keratinocytes. Highest levels found in liver, mammary gland and brain.

Activity regulation. Inhibited by hexestrol with an IC(50) of 9.5 uM, 1,10-phenanthroline with an IC(50) of 55 uM, 1,7-phenanthroline with an IC(50) of 72 uM, flufenamic acid with an IC(50) of 6.0 uM, indomethacin with an IC(50) of 140 uM, ibuprofen with an IC(50) of 950 uM, lithocholic acid with an IC(50) of 25 uM, ursodeoxycholic acid with an IC(50) of 340 uM and chenodeoxycholic acid with an IC(50) of 570 uM. The oxidation reaction is inhibited by low micromolar concentrations of NADPH. Inhibited by benzodiazepines.

Pathway. Steroid metabolism.

Similarity. Belongs to the aldo/keto reductase family.

RefSeq proteins (1): NP_001344* (*=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
IPR044482	AKR1C	Family

Pfam: PF00248

Enzyme classification (BRENDA):

• EC 1.1.1.149 — 20alpha-hydroxysteroid dehydrogenase (BRENDA: 14 organisms, 224 substrates, 179 inhibitors, 237 Km, 77 kcat entries)
• EC 1.1.1.270 — 3beta-hydroxysteroid 3-dehydrogenase (BRENDA: 11 organisms, 123 substrates, 36 inhibitors, 43 Km, 32 kcat entries)
• EC 1.1.1.357 — 3alpha-hydroxysteroid 3-dehydrogenase (BRENDA: 8 organisms, 118 substrates, 31 inhibitors, 151 Km, 108 kcat entries)
• EC 1.1.1.50 — 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific) (BRENDA: 17 organisms, 293 substrates, 102 inhibitors, 177 Km, 105 kcat entries)
• EC 1.3.1.20 — trans-1,2-dihydrobenzene-1,2-diol dehydrogenase (BRENDA: 13 organisms, 160 substrates, 113 inhibitors, 105 Km, 72 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
CAMPHORQUINONE	0.1–26	24
ANDROSTERONE	0.0001–0.21	16
PROGESTERONE	0.0006–0.2833	15
D-XYLOSE	0.8–213	15
5ALPHA-DIHYDROTESTOSTERONE	0.0001–0.071	12
NAD+	0.0031–0.87	11
20ALPHA-HYDROXYPROGESTERONE	0.0012–2.5	10
CHOLIC ACID	0.025–586	10
NADPH	0.0002–0.052	9
NADP+	0.0007–0.025	8
ANDROSTERONE	0.0005–14	8
NAD+	0.081–1.2	8
TRANS-BENZENE DIHYDRODIOL	0.017–2.6	8
5ALPHA-DIHYDROTESTOSTERONE	0.0012–0.071	7
DIHYDROTESTOSTERONE	0.0011–0.016	7

Catalyzed reactions (Rhea), 12 shown:

• testosterone + NADP(+) = androst-4-ene-3,17-dione + NADPH + H(+) (RHEA:14981)
• (17R,20S)-17,20-dihydroxypregn-4-en-3-one + NAD(+) = 17alpha-hydroxyprogesterone + NADH + H(+) (RHEA:15853)
• (17R,20S)-17,20-dihydroxypregn-4-en-3-one + NADP(+) = 17alpha-hydroxyprogesterone + NADPH + H(+) (RHEA:15857)
• 5alpha-androstane-3beta,17beta-diol + NADP(+) = 17beta-hydroxy-5alpha-androstan-3-one + NADPH + H(+) (RHEA:16297)
• (S)-indan-1-ol + NAD(+) = indan-1-one + NADH + H(+) (RHEA:16317)
• (S)-indan-1-ol + NADP(+) = indan-1-one + NADPH + H(+) (RHEA:16321)
• (1R,2R)-1,2-dihydrobenzene-1,2-diol + NADP(+) = catechol + NADPH + H(+) (RHEA:16729)
• androsterone + NADP(+) = 5alpha-androstan-3,17-dione + NADPH + H(+) (RHEA:20377)
• 3beta-hydroxy-5beta-pregnane-20-one + NADP(+) = 5beta-pregnan-3,20-dione + NADPH + H(+) (RHEA:22944)
• 17beta-estradiol + NAD(+) = estrone + NADH + H(+) (RHEA:24612)
• 17beta-estradiol + NADP(+) = estrone + NADPH + H(+) (RHEA:24616)
• a 3alpha-hydroxysteroid + NADP(+) = a 3-oxosteroid + NADPH + H(+) (RHEA:34783)

UniProt features (61 total): helix 17, strand 12, binding site 10, mutagenesis site 7, sequence conflict 7, site 3, sequence variant 2, chain 1, active site 1, turn 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
1MRQ	X-RAY DIFFRACTION	1.59
3C3U	X-RAY DIFFRACTION	1.8
8JP2	X-RAY DIFFRACTION	1.8
3NTY	X-RAY DIFFRACTION	1.87
3GUG	X-RAY DIFFRACTION	1.9
6IJX	X-RAY DIFFRACTION	2.2
6A7A	X-RAY DIFFRACTION	2.37
4YVP	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q04828-F1	97.63	0.98

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 (4): 55 (proton donor); 54 (important for substrate specificity); 84 (lowers pka of active site tyr); 222 (may be involved in the mediating step between the transformation of progesterone and the release of the cofactor)

Ligand- & substrate-binding residues (10): 227; 270–280; 20–24; 24; 50; 117; 166–167; 190; 216–222; 222

Mutagenesis-validated functional residues (7):

Position	Phenotype
127	30-fold decrease in k(cat)/k(m) value for progesterone reduction; no effect on the k(m) value.
222	marked decrease in k(cat)/k(m) value for progesterone; 24-fold decrease for progesterone reduction; 18-fold decrease for
222	marked decrease in k(cat)/k(m) value for progesterone; 10-fold decrease for progesterone reduction; 3-fold decrease for
304	70-fold decrease in progesterone reduction. no effect on dht reduction.
305	no effect on progesterone reduction.
307	no effect on progesterone reduction.
309	no effect on progesterone reduction.

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-193368	Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-193775	Synthesis of bile acids and bile salts via 24-hydroxycholesterol
R-HSA-193807	Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-HSA-975634	Retinoid metabolism and transport
R-HSA-9757110	Prednisone ADME
R-HSA-1430728	Metabolism
R-HSA-192105	Synthesis of bile acids and bile salts
R-HSA-194068	Bile acid and bile salt metabolism
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-2187338	Visual phototransduction
R-HSA-556833	Metabolism of lipids
R-HSA-6806667	Metabolism of fat-soluble vitamins
R-HSA-8957322	Metabolism of steroids
R-HSA-9709957	Sensory Perception
R-HSA-9748784	Drug ADME

MSigDB gene sets: 290 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, MODULE_93, LI_CISPLATIN_RESISTANCE_DN, GOBP_DIGESTION, GOBP_EPITHELIUM_DEVELOPMENT, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_STEROL_HOMEOSTASIS, GOBP_CELLULAR_RESPONSE_TO_LIPID, JAEGER_METASTASIS_DN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOZGIT_ESR1_TARGETS_DN, GOBP_C21_STEROID_HORMONE_METABOLIC_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS

GO Biological Process (20): retinoid metabolic process (GO:0001523), prostaglandin metabolic process (GO:0006693), xenobiotic metabolic process (GO:0006805), digestion (GO:0007586), bile acid metabolic process (GO:0008206), bile acid and bile salt transport (GO:0015721), intestinal cholesterol absorption (GO:0030299), epithelial cell differentiation (GO:0030855), progesterone metabolic process (GO:0042448), retinal metabolic process (GO:0042574), cholesterol homeostasis (GO:0042632), daunorubicin metabolic process (GO:0044597), doxorubicin metabolic process (GO:0044598), cellular response to jasmonic acid stimulus (GO:0071395), positive regulation of reactive oxygen species metabolic process (GO:2000379), alcohol metabolic process (GO:0006066), lipid metabolic process (GO:0006629), steroid metabolic process (GO:0008202), monocarboxylic acid metabolic process (GO:0032787), hormone metabolic process (GO:0042445)

GO Molecular Function (20): aldose reductase (NADPH) activity (GO:0004032), estradiol 17-beta-dehydrogenase [NAD(P)+] activity (GO:0004303), alcohol dehydrogenase (NADP+) activity (GO:0008106), oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor (GO:0016655), carboxylic acid binding (GO:0031406), bile acid binding (GO:0032052), 3-beta-hydroxy-5-beta-steroid dehydrogenase (NADP+) activity (GO:0033703), steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0033764), 17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase [NAD(P)+] activity (GO:0047006), androsterone dehydrogenase [NAD(P)+] activity (GO:0047023), 5-alpha-androstane-3-beta,17-beta-diol dehydrogenase (NADP+) activity (GO:0047024), androstan-3-alpha,17-beta-diol dehydrogenase (NAD+) activity (GO:0047044), testosterone dehydrogenase (NADP+) activity (GO:0047045), ketosteroid monooxygenase activity (GO:0047086), trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity (GO:0047115), indanol dehydrogenase activity (GO:0047718), 3-alpha-hydroxysteroid 3-dehydrogenase [NAD(P)+] activity (GO:0140169), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), obsolete testosterone dehydrogenase [NAD(P)+] activity (GO:0030283)

GO Cellular Component (3): cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Synthesis of bile acids and bile salts	3
Metabolism	2
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1
Drug ADME	1
Bile acid and bile salt metabolism	1
Metabolism of steroids	1
Sensory Perception	1
Metabolism of vitamins and cofactors	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	7
ketone metabolic process	3
metabolic process	2
olefinic compound metabolic process	2
glycoside metabolic process	2
polyketide metabolic process	2
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	2
cellular anatomical structure	2
diterpenoid metabolic process	1
prostanoid metabolic process	1
cellular response to xenobiotic stimulus	1
multicellular organismal process	1
steroid metabolic process	1
monocarboxylic acid metabolic process	1
lipid transport	1
monocarboxylic acid transport	1
organic hydroxy compound transport	1
lipid digestion	1
intestinal lipid absorption	1
cell differentiation	1
epithelium development	1
C21-steroid hormone metabolic process	1
retinoid metabolic process	1
aldehyde metabolic process	1
sterol homeostasis	1
primary alcohol metabolic process	1
tertiary alcohol metabolic process	1
response to jasmonic acid	1
cellular response to hormone stimulus	1
cellular response to fatty acid	1
positive regulation of metabolic process	1
reactive oxygen species metabolic process	1
regulation of reactive oxygen species metabolic process	1
small molecule metabolic process	1
primary metabolic process	1
lipid metabolic process	1
carboxylic acid metabolic process	1
regulation of hormone levels	1
alcohol dehydrogenase (NADP+) activity	1
alcohol dehydrogenase [NAD(P)+] activity	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

35 interactions, top by confidence:

A	B	Type	Score
PTPN3	AKR1C1	psi-mi:“MI:0915”(physical association)	0.720
AKR1C1	PTPN3	psi-mi:“MI:0915”(physical association)	0.720
AKR1C2	AKR1C4	psi-mi:“MI:0914”(association)	0.640
AKR1C3	AKR1C4	psi-mi:“MI:0914”(association)	0.620
AKR1C1	AKR1D1	psi-mi:“MI:0915”(physical association)	0.590
AKR1C1	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
AKR1C2	AKR1C3	psi-mi:“MI:0914”(association)	0.530
TMEM59	B4GALT5	psi-mi:“MI:0914”(association)	0.530
COMMD8	AKR1C1	psi-mi:“MI:0915”(physical association)	0.370
AKR1C2	IPO8	psi-mi:“MI:0914”(association)	0.350
	AP3B1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
PIK3C2A	ACTN4	psi-mi:“MI:0914”(association)	0.350
FNDC5	A2ML1	psi-mi:“MI:0914”(association)	0.350
AKR1C2	BRD4	psi-mi:“MI:0914”(association)	0.350
AVPI1		psi-mi:“MI:0914”(association)	0.350
HOXB6	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
IL5RA	LETM1	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
ZC3HC1	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (38): PTPN3 (Two-hybrid), AKR1C1 (Affinity Capture-MS), AKR1C1 (Affinity Capture-MS), AKR1D1 (Affinity Capture-MS), AKR1C1 (Two-hybrid), TFF3 (Two-hybrid), AKR1C1 (Affinity Capture-Western), AKR1C1 (Affinity Capture-MS), AKR1C1 (Affinity Capture-MS), AKR1D1 (Affinity Capture-MS), AKR1C1 (Proximity Label-MS), AKR1C1 (Two-hybrid), AKR1C1 (Protein-RNA), AKR1C1 (Proximity Label-MS), AKR1C1 (Proximity Label-MS)

ESM2 similar proteins: A6QP05, B0BNF8, B2GV72, O00764, O14756, O35331, O54753, O54909, O75452, O75828, O88451, P16152, P17516, P42330, P46597, P47727, P47844, P48758, P50170, P52895, P55006, P80508, Q04828, Q1XAA8, Q28960, Q3SZD7, Q3SZM9, Q3T001, Q3U0B3, Q3ZBV9, Q5R7C9, Q5RCU5, Q5REQ0, Q6SKR2, Q6UWP2, Q6W8P9, Q71R50, Q8C436, Q8HZJ0, Q8K183

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

1 interactions.

A	Effect	B	Mechanism
hexestrol	down-regulates	AKR1C1	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	56
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
545134	Single allele	Likely pathogenic

SpliceAI

1044 predictions. Top by Δscore:

Variant	Effect	Δscore
10:4963807:G:GT	donor_gain	1.0000
10:4966925:A:AG	acceptor_gain	1.0000
10:4966926:G:GG	acceptor_gain	1.0000
10:4967039:TAAAG:T	donor_loss	1.0000
10:4967040:AAAGG:A	donor_loss	1.0000
10:4967041:AAGG:A	donor_loss	1.0000
10:4967042:AGGT:A	donor_loss	1.0000
10:4967043:GGTAG:G	donor_loss	1.0000
10:4967045:T:G	donor_loss	1.0000
10:4968818:CCAG:C	acceptor_loss	1.0000
10:4968820:A:AG	acceptor_gain	1.0000
10:4968820:A:C	acceptor_loss	1.0000
10:4968820:AG:A	acceptor_gain	1.0000
10:4968820:AGGCC:A	acceptor_gain	1.0000
10:4968821:G:GG	acceptor_gain	1.0000
10:4968821:GG:G	acceptor_gain	1.0000
10:4968821:GGCC:G	acceptor_gain	1.0000
10:4968821:GGCCG:G	acceptor_gain	1.0000
10:4968940:ACCAG:A	donor_gain	1.0000
10:4968941:CCAG:C	donor_gain	1.0000
10:4968942:CAG:C	donor_gain	1.0000
10:4968943:AG:A	donor_gain	1.0000
10:4968944:GG:G	donor_gain	1.0000
10:4968945:G:GG	donor_gain	1.0000
10:4972327:G:GT	donor_gain	1.0000
10:4972579:TCCA:T	acceptor_loss	1.0000
10:4972580:CCA:C	acceptor_loss	1.0000
10:4972582:A:AG	acceptor_gain	1.0000
10:4972582:A:AT	acceptor_loss	1.0000
10:4972582:AG:A	acceptor_gain	1.0000

AlphaMissense

2109 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:4966081:G:C	K84N	0.992
10:4966081:G:T	K84N	0.992
10:4968381:T:A	W148R	0.988
10:4968381:T:C	W148R	0.988
10:4968383:G:C	W148C	0.986
10:4968383:G:T	W148C	0.986
10:4968876:T:C	F168L	0.985
10:4968878:C:A	F168L	0.985
10:4968878:C:G	F168L	0.985
10:4965979:T:A	D50E	0.984
10:4965979:T:G	D50E	0.984
10:4966067:T:C	F80L	0.983
10:4966069:C:A	F80L	0.983
10:4966069:C:G	F80L	0.983
10:4968875:C:A	N167K	0.983
10:4968875:C:G	N167K	0.983
10:4966080:A:C	K84T	0.980
10:4972714:A:C	S271R	0.980
10:4972716:C:A	S271R	0.980
10:4972716:C:G	S271R	0.980
10:4965980:T:C	S51P	0.979
10:4967012:T:C	L113P	0.978
10:4972289:G:A	G220E	0.978
10:4965978:A:T	D50V	0.977
10:4966080:A:T	K84M	0.976
10:4977725:T:C	F319L	0.976
10:4977727:T:A	F319L	0.976
10:4977727:T:G	F319L	0.976
10:4965965:T:C	F46L	0.974
10:4965967:C:A	F46L	0.974

dbSNP variants (sampled 300 via entrez): RS1000884837 (10:4965230 G>A), RS1000946235 (10:4969804 AT>A,ATT), RS1001177154 (10:4964236 G>T), RS1001280493 (10:4963587 C>G), RS1001324190 (10:4968612 C>G), RS1002895765 (10:4962356 T>A,C), RS1002947005 (10:4967614 G>C), RS1002999470 (10:4967343 C>T), RS1003237490 (10:4983215 C>T), RS1003252514 (10:4962790 T>C), RS1003331873 (10:4966488 T>C), RS1003337783 (10:4966240 A>T), RS1003888837 (10:4969840 T>G), RS1005065876 (10:4965502 G>A,C,T), RS1005177509 (10:4970177 C>T)

Disease associations

OMIM: gene MIM:600449 | disease phenotypes: MIM:181500

GenCC curated gene-disease

Mondo (1): schizophrenia (MONDO:0005090)

Orphanet (1): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0100753	Schizophrenia

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST001515_3	Economic and political preferences (immigration/crime)	6.000000e-06
GCST002647_35	Height	2.000000e-15
GCST004748_18	Lung cancer	2.000000e-06
GCST004750_31	Squamous cell lung carcinoma	2.000000e-06
GCST009391_1751	Metabolite levels	5.000000e-06
GCST009391_1760	Metabolite levels	3.000000e-06
GCST010285_2	Hypopharyngeal or laryngeal cancer	1.000000e-07
GCST012226_101	Waist circumference adjusted for body mass index	8.000000e-12
GCST012226_102	Waist circumference adjusted for body mass index	2.000000e-09
GCST012228_392	Waist-hip index	5.000000e-19
GCST012228_393	Waist-hip index	1.000000e-09
GCST012228_394	Waist-hip index	4.000000e-12
GCST012228_395	Waist-hip index	1.000000e-13
GCST012228_396	Waist-hip index	1.000000e-08
GCST012229_130	Hip index	3.000000e-08
GCST012229_131	Hip index	1.000000e-08
GCST012229_79	Hip index	2.000000e-12
GCST012230_69	Waist-to-hip ratio adjusted for BMI	2.000000e-16
GCST012230_70	Waist-to-hip ratio adjusted for BMI	7.000000e-09
GCST012230_71	Waist-to-hip ratio adjusted for BMI	5.000000e-11
GCST012230_72	Waist-to-hip ratio adjusted for BMI	1.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004827	economic and social preference
EFO:0010369	lysophosphatidylethanolamine 18:2 measurement
EFO:0010370	lysophosphatidylethanolamine 20:4 measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5905 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

9 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 555,929 (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
CHEMBL12	DIAZEPAM	4	92,281
CHEMBL1481	GLIMEPIRIDE	4	33,335
CHEMBL388590	BENZBROMARONE	4	8,245
CHEMBL509	MECLOFENAMIC ACID	4	45,809
CHEMBL563	FLURBIPROFEN	4	71,809
CHEMBL6	INDOMETHACIN	4	156,366
CHEMBL686	MEFENAMIC ACID	4	61,835
CHEMBL717	MEDROXYPROGESTERONE ACETATE	4	51,452
CHEMBL23588	FLUFENAMIC ACID	2	34,797

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

Binding affinities (BindingDB)

17 measured of 31 human assays (31 total across all organisms); most potent 17 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[1-(4-chlorobenzoyl)-5-methoxy-3-methylindol-2-yl]propanoic acid	IC50	17.7 nM	US-9346803: Indomethacin analogs for the treatment of castrate-resistant prostate cancer
3-[1-(4-chlorobenzoyl)-3-ethyl-5-methoxyindol-2-yl]propanoic acid	IC50	30.7 nM	US-9346803: Indomethacin analogs for the treatment of castrate-resistant prostate cancer
3,5-dichloro-2-hydroxybenzoic acid	KI	58 nM
9-(4-chlorobenzoyl)-6-methoxy-1,2,3,4-tetrahydrocarbazole-3-carboxylic acid	IC50	76.2 nM	US-9346803: Indomethacin analogs for the treatment of castrate-resistant prostate cancer
3-[1-(4-chlorobenzoyl)-5-methoxy-3-methylindol-2-yl]-N-methylsulfonylpropanamide	IC50	100 nM	US-9346803: Indomethacin analogs for the treatment of castrate-resistant prostate cancer
2-[1-[4-(chloromethyl)benzoyl]-5-methoxy-2-methylindol-3-yl]acetic acid	IC50	100 nM	US-9346803: Indomethacin analogs for the treatment of castrate-resistant prostate cancer
(6alpha)-17-(Acetyloxy)-6-methylpreg-4-ene-3,20-dione	IC50	700 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid	IC50	980 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
3-(2,4-dinitroanilino)benzoic acid	KI	2660 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
DIAZEPAM	IC50	5600 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
2-(2-Hydroxyphenyl)-4H-chromen-4-one (3d)	IC50	6200 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
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-chlorophenyl)amino]benzoic acid	IC50	30200 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
2-[2-nitro-5-(trifluoromethyl)anilino]benzoic acid	IC50	50000 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof
2-[(1R,2R)-3-oxo-2-[(Z)-pent-2-enyl]cyclopentyl]acetic acid	KI	106000 nM	US-9271961: Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof

ChEMBL bioactivities

141 potent at pChembl≥5 of 222 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.07	Ki	0.86	nM	CHEMBL1275703
9.07	Ki	0.85	nM	CHEMBL1275703
8.92	Ki	1.2	nM	CHEMBL1275703
8.89	Ki	1.3	nM	CHEMBL1275704
8.89	Ki	1.3	nM	CHEMBL1275725
8.82	Ki	1.5	nM	CHEMBL1275703
8.77	Ki	1.7	nM	CHEMBL1275703
8.70	Ki	2	nM	CHEMBL1277648
8.68	Ki	2.1	nM	CHEMBL1277647
8.59	Ki	2.6	nM	CHEMBL1275723
8.40	Ki	4	nM	CHEMBL387536
8.39	Ki	4.1	nM	CHEMBL387536
8.32	Ki	4.8	nM	CHEMBL1275703
8.23	Ki	5.9	nM	CHEMBL449129
8.22	IC50	6	nM	CHEMBL449129
8.18	Ki	6.6	nM	CHEMBL449129
8.15	Ki	7	nM	CHEMBL449129
8.05	Ki	9	nM	CHEMBL447448
7.85	Ki	14	nM	CHEMBL387536
7.54	Ki	29	nM	CHEMBL1277741
7.48	IC50	33	nM	CHEMBL521800
7.40	IC50	40	nM	CHEMBL6144459
7.40	IC50	40	nM	CHEMBL6151784
7.32	IC50	48	nM	BENZBROMARONE
7.28	Kd	52.15	nM	CHEMBL5653589
7.28	ED50	52.15	nM	CHEMBL5653589
7.24	Ki	58	nM	CHEMBL449129
7.19	Ki	64	nM	CHEMBL1275724
7.16	Ki	70	nM	CHEMBL1275703
7.11	Ki	78	nM	CHEMBL449129
7.07	Ki	85	nM	CHEMBL449129
7.05	IC50	90	nM	CHEMBL6162926
7.02	Ki	96	nM	CHEMBL1277740
7.00	IC50	100	nM	CHEMBL6169938
7.00	IC50	100	nM	CHEMBL6175880
7.00	IC50	100	nM	CHEMBL1275703
6.95	Ki	113	nM	CHEMBL387536
6.85	Ki	140	nM	CHEMBL331146
6.68	IC50	210	nM	CHEMBL6160647
6.57	Ki	270	nM	CHEMBL449129
6.52	IC50	300	nM	CHEMBL1275725
6.47	Ki	340	nM	CHEMBL1277646
6.39	IC50	411	nM	CHEMBL4293881
6.36	IC50	433	nM	CHEMBL4291554
6.35	IC50	443	nM	CHEMBL4287291
6.34	IC50	460	nM	CHEMBL387536
6.33	IC50	462	nM	CHEMBL4294478
6.33	IC50	470	nM	CHEMBL5203670
6.31	IC50	487	nM	CHEMBL4294539
6.31	IC50	490	nM	CHEMBL6174124

PubChem BioAssay actives

108 with measured affinity, of 532 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
3-chloro-2-hydroxy-5-phenylbenzoic acid	591009: Competitive inhibition of human recombinant AKR1C1 Phe311Leu mutant by fluorescence assay	ki	0.0008	uM
3-fluoro-2-hydroxy-5-phenylbenzoic acid	536798: Inhibition of human wild type AKR1C1 dehydrogenase activity by fluorometric assay	ki	0.0013	uM
3-chloro-2-hydroxy-5-(3-methylphenyl)benzoic acid	536798: Inhibition of human wild type AKR1C1 dehydrogenase activity by fluorometric assay	ki	0.0013	uM
3-chloro-2-hydroxy-5-[4-(2-methylpropyl)phenyl]benzoic acid	536798: Inhibition of human wild type AKR1C1 dehydrogenase activity by fluorometric assay	ki	0.0020	uM
5-(4-butylphenyl)-3-chloro-2-hydroxybenzoic acid	536798: Inhibition of human wild type AKR1C1 dehydrogenase activity by fluorometric assay	ki	0.0021	uM
3-chloro-2-hydroxy-5-(4-methylphenyl)benzoic acid	536798: Inhibition of human wild type AKR1C1 dehydrogenase activity by fluorometric assay	ki	0.0026	uM
3-bromo-2-hydroxy-5-phenylbenzoic acid	350172: Inhibition of human recombinant 20-alpha HSD expressed in Escherichia coli JM109	ki	0.0040	uM
3,5-dichloro-2-hydroxybenzoic acid	1798661: Assay of Enzyme Activity from Article 10.1021/jm8003575: “Selectivity determinants of inhibitor binding to human 20alpha-hydroxysteroid dehydrogenase: crystal structure of the enzyme in ternary complex with coenzyme and the potent inhibitor 3,5-dichlorosalicylic acid.”	ki	0.0059	uM
3,5-Dibromosalicylic acid	350172: Inhibition of human recombinant 20-alpha HSD expressed in Escherichia coli JM109	ki	0.0090	uM
3-chloro-2-hydroxy-5-[4-(trifluoromethoxy)phenyl]benzoic acid	536798: Inhibition of human wild type AKR1C1 dehydrogenase activity by fluorometric assay	ki	0.0290	uM
3,3-bis(3,5-dibromo-4-hydroxyphenyl)-2-benzofuran-1-one	350176: Inhibition of 20-alpha HSD	ic50	0.0330	uM
(3,5-dibromo-4-hydroxyphenyl)-(2-ethyl-1-benzofuran-3-yl)methanone	350176: Inhibition of 20-alpha HSD	ic50	0.0480	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147832: Binding affinity to human AKR1C1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0522	uM
3-chloro-2-hydroxy-5-(2-phenylethynyl)benzoic acid	536798: Inhibition of human wild type AKR1C1 dehydrogenase activity by fluorometric assay	ki	0.0640	uM
5-(4-tert-butylphenyl)-3-chloro-2-hydroxybenzoic acid	536798: Inhibition of human wild type AKR1C1 dehydrogenase activity by fluorometric assay	ki	0.0960	uM
5-bromo-2-hydroxy-3-phenylbenzoic acid	350172: Inhibition of human recombinant 20-alpha HSD expressed in Escherichia coli JM109	ki	0.1400	uM
3-chloro-2-hydroxy-5-[4-(1-methoxyethyl)phenyl]benzoic acid	536798: Inhibition of human wild type AKR1C1 dehydrogenase activity by fluorometric assay	ki	0.3400	uM
6-amino-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-3-propyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	0.4110	uM
6-amino-3-(2-cyclopentylethyl)-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	0.4330	uM
6-amino-3-(2-cyclohexylethyl)-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	0.4430	uM
6-amino-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-1-methyl-3-propyl-4H-pyrano[3,2-d]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	0.4620	uM
7-[2-[(6-oxo-4-propyl-1H-pyrimidin-2-yl)sulfanyl]acetyl]-1,3,4,5-tetrahydro-1-benzazepin-2-one	1874809: Inhibition of human recombinant AKR1C1 transfected in Escherichia coli BL21 (DE3) pLysS competent cells assessed as inhibition of NADP+ dependent oxidation of S-tetralol using S-tetralol as substrate incubated for 10 mins by fluorescence microplate reader assay	ic50	0.4700	uM
6-amino-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	0.4870	uM
6-amino-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-3-pentyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	0.5310	uM
6-amino-3-hexyl-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	0.5340	uM
6-amino-4-(4-hydroxy-3-nitrophenyl)-3-propyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	0.6610	uM
1-[4-(3-phenylphenyl)phenyl]sulfonylpiperidine-3-carboxylic acid	703402: Inhibition of human recombinant N-terminal His6-tagged AKR1C1 expressed in Escherichia coli BL21(DE3) cells using 8-Acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-aza-benzo[de]anthracen-10-one as substrate after 1 hr by fluorimetric analysis	ic50	0.7300	uM
Meclofenamic Acid	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	0.7400	uM
3-[(8-chloro-3,4-dihydro-1H-isoquinolin-2-yl)sulfonyl]benzoic acid	703402: Inhibition of human recombinant N-terminal His6-tagged AKR1C1 expressed in Escherichia coli BL21(DE3) cells using 8-Acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-aza-benzo[de]anthracen-10-one as substrate after 1 hr by fluorimetric analysis	ic50	0.7400	uM
6-amino-3-ethyl-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	0.7900	uM
6-amino-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-3-(3-phenylpropyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	0.8010	uM
6-amino-3-butyl-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	0.8100	uM
Mefenamic Acid	703563: Inhibition of human recombinant AKR1C1 assessed as 1-acenaphthenol oxidation by spectrophotometry	ki	0.8100	uM
1-(4-bromophenyl)sulfonylindole-3-carboxylic acid	703402: Inhibition of human recombinant N-terminal His6-tagged AKR1C1 expressed in Escherichia coli BL21(DE3) cells using 8-Acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-aza-benzo[de]anthracen-10-one as substrate after 1 hr by fluorimetric analysis	ic50	0.8300	uM
6-amino-3-(2,2-dimethylpropyl)-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	0.8440	uM
6-amino-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-3-(3-methylbutyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	0.8700	uM
7-hydroxy-N-[3-(4-hydroxyphenyl)propyl]-2-oxochromene-3-carboxamide	1465663: Inhibition of recombinant human AKR1C1 using S-tetralol as substrate	ic50	0.9500	uM
6-amino-1-cyclopentyl-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-3-propyl-4H-pyrano[3,2-d]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	1.0500	uM
6-amino-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-1-(oxolan-3-yl)-3-propyl-4H-pyrano[3,2-d]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	1.0900	uM
3-[4-(3,5-dichlorophenyl)-3-(trifluoromethyl)phenyl]pentan-2-one	1997377: Inhibition of human recombinant AKR1C1 transfected in Escherichia coli BL21 (DE3) pLysS competent cells using S-tetralol as substrate assessed as inhibition of NADP+ dependent substrate oxidation incubated for 10 mins by fluorescence microplate reader assay	ic50	1.1500	uM
6-amino-3-heptyl-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	1.2000	uM
6-amino-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-3-(4-methylpentyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	1.2100	uM
6-amino-1-(2-fluorophenyl)-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-3-propyl-4H-pyrano[3,2-d]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	1.2700	uM
Medroxyprogesterone Acetate	735521: Inhibition of human recombinant AKR1C1 expressed in Escherichia coli assessed as decrease in oxidation of 1-acenaphthenol substrate by spectrophotometric analysis	ic50	1.8000	uM
Flurbiprofen	1997377: Inhibition of human recombinant AKR1C1 transfected in Escherichia coli BL21 (DE3) pLysS competent cells using S-tetralol as substrate assessed as inhibition of NADP+ dependent substrate oxidation incubated for 10 mins by fluorescence microplate reader assay	ic50	2.0500	uM
2-[4-(3-fluoro-4-methylphenyl)-3-(trifluoromethyl)phenyl]butanoic acid	1997377: Inhibition of human recombinant AKR1C1 transfected in Escherichia coli BL21 (DE3) pLysS competent cells using S-tetralol as substrate assessed as inhibition of NADP+ dependent substrate oxidation incubated for 10 mins by fluorescence microplate reader assay	ic50	2.0600	uM
6-amino-4-(4-hydroxy-3-methoxyphenyl)-3-propyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	2.4900	uM
6-amino-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-3-propyl-1-pyridin-2-yl-4H-pyrano[3,2-d]pyrazole-5-carbonitrile	1419334: Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 cells in presence of 9,10-phenanthrenequinone and NADPH by fluorescence assay	ic50	2.5200	uM
2-[3-(trifluoromethyl)anilino]benzoic acid	703402: Inhibition of human recombinant N-terminal His6-tagged AKR1C1 expressed in Escherichia coli BL21(DE3) cells using 8-Acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-aza-benzo[de]anthracen-10-one as substrate after 1 hr by fluorimetric analysis	ic50	2.6400	uM
5-[[(6-ethoxy-3,4-dihydro-2H-chromene-3-carbonyl)-methylamino]methyl]-2-methylfuran-3-carboxylic acid	1874809: Inhibition of human recombinant AKR1C1 transfected in Escherichia coli BL21 (DE3) pLysS competent cells assessed as inhibition of NADP+ dependent oxidation of S-tetralol using S-tetralol as substrate incubated for 10 mins by fluorescence microplate reader assay	ic50	2.8800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects response to substance, affects cotreatment, increases activity, increases reaction, decreases expression (+1 more)	11
sodium arsenite	affects reaction, affects expression, increases abundance, increases expression	9
Tobacco Smoke Pollution	decreases expression, increases expression	7
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	7
Progesterone	affects reduction, increases reduction, decreases expression, affects metabolic processing, decreases activity	6
Valproic Acid	affects cotreatment, increases expression	5
9,10-phenanthrenequinone	increases reduction, affects activity, increases metabolic processing	4
bisphenol A	increases expression, affects expression, decreases expression, decreases methylation	4
sulforaphane	increases expression, affects reaction	4
Air Pollutants	increases abundance, increases expression, decreases expression	4
Cisplatin	decreases reaction, increases reaction, decreases response to substance, affects cotreatment, increases expression	4
Flufenamic Acid	decreases activity, affects response to substance, decreases reaction, increases metabolic processing	4
Indomethacin	decreases activity, affects cotreatment, decreases expression, increases expression	4
Medroxyprogesterone Acetate	decreases activity, decreases expression, increases expression	4
Cadmium Chloride	increases abundance, increases expression	4
trichostatin A	increases expression, affects cotreatment	3
acenaphthene-1-ol	affects cotreatment, increases oxidation, increases metabolic processing, decreases reaction	3
bisphenol S	decreases expression, increases expression, affects cotreatment	3
Arsenic Trioxide	decreases response to substance, affects cotreatment, increases expression, affects binding, decreases reaction	3
Cadmium	increases abundance, increases expression	3
Hydrogen Peroxide	decreases expression, increases abundance, increases expression	3
Meclofenamic Acid	decreases activity	3
beta-Naphthoflavone	increases expression	3
quinomethionate	affects expression, increases expression	2
lead acetate	increases expression	2
cobaltous chloride	affects cotreatment, increases expression	2
2-tert-butylhydroquinone	increases expression	2
tetralol	affects oxidation, increases metabolic processing	2
perfluorooctanoic acid	decreases expression	2
1,10-phenanthroline	decreases activity	2

ChEMBL screening assays

100 unique, capped per target: 91 binding, 9 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1033524	Binding	Inhibition of human recombinant GST-tagged AKR1C1 expressed in Escherichia coli BL21 at 100 uM	New cyclopentane derivatives as inhibitors of steroid metabolizing enzymes AKR1C1 and AKR1C3. — Eur J Med Chem
CHEMBL4339427	ADMET	Inhibition of recombinant human AKR1C1 expressed in Escherichia coli BL21 (D3) at 200 uM using S-tetralol as substrate in presence of NADP+ by UV-spectrophotometric method relative to control	Potent and Highly Selective Aldo-Keto Reductase 1C3 (AKR1C3) Inhibitors Act as Chemotherapeutic Potentiators in Acute Myeloid Leukemia and T-Cell Acute Lymphoblastic Leukemia. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1RJ	Abcam U-87MG AKR1C1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety