HSD17B1

Summary

HSD17B1 (hydroxysteroid 17-beta dehydrogenase 1, HGNC:5210) is a protein-coding gene on chromosome 17q21.2, encoding 17-beta-hydroxysteroid dehydrogenase type 1 (P14061). Favors the reduction of estrogens and androgens.

This gene encodes a member of the 17beta-hydroxysteroid dehydrogenase family of short-chain dehydrogenases/reductases. It has a dual function in estrogen activation and androgen inactivation and plays a major role in establishing the estrogen E2 concentration gradient between serum and peripheral tissues. The encoded protein catalyzes the last step in estrogen activation, using NADPH to convert estrogens E1 and E2 and androgens like 4-androstenedione, to testosterone. It has an N-terminal short-chain dehydrogenase domain with a cofactor binding site, and a narrow, hydrophobic C-terminal domain with a steroid substrate binding site. This gene is expressed primarily in the placenta and ovarian granulosa cells, and to a lesser extent, in the endometrium, adipose tissue, and prostate. Polymorphisms in this gene have been linked to breast and prostate cancer. A pseudogene of this gene has been identified. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3292 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 86 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000413

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5210
Approved symbol	HSD17B1
Name	hydroxysteroid 17-beta dehydrogenase 1
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	HSD17, MGC138140, SDR28C1
Ensembl gene	ENSG00000108786
Ensembl biotype	protein_coding
OMIM	109684
Entrez	3292

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000225929, ENST00000585807, ENST00000587280, ENST00000590299, ENST00000593215

RefSeq mRNA: 2 — MANE Select: NM_000413 NM_000413, NM_001330219

CCDS: CCDS11428, CCDS82126

Canonical transcript exons

ENST00000585807 — 6 exons

Exon	Start	End
ENSE00000726150	42553439	42553618
ENSE00001644230	42553794	42553887
ENSE00003581355	42554405	42554582
ENSE00003630765	42552923	42553030
ENSE00003653922	42553124	42553291
ENSE00003902346	42554669	42555214

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 94.66.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3646 / max 395.0727, expressed in 18 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160955	0.3646	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	94.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.38	gold quality
lower esophagus mucosa	UBERON:0035834	80.20	gold quality
esophagus mucosa	UBERON:0002469	73.44	gold quality
left ovary	UBERON:0002119	73.39	gold quality
skin of abdomen	UBERON:0001416	72.96	gold quality
skin of leg	UBERON:0001511	72.63	gold quality
right ovary	UBERON:0002118	72.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.34	gold quality
stromal cell of endometrium	CL:0002255	71.04	gold quality
zone of skin	UBERON:0000014	70.90	gold quality
omental fat pad	UBERON:0010414	69.40	gold quality
peritoneum	UBERON:0002358	69.33	gold quality
adipose tissue of abdominal region	UBERON:0007808	68.93	gold quality
esophagus	UBERON:0001043	67.84	gold quality
mucosa of transverse colon	UBERON:0004991	67.77	gold quality
ovary	UBERON:0000992	67.73	gold quality
esophagus squamous epithelium	UBERON:0006920	67.26	gold quality
left coronary artery	UBERON:0001626	66.73	gold quality
epithelium of esophagus	UBERON:0001976	65.27	gold quality
prefrontal cortex	UBERON:0000451	65.22	gold quality
adipose tissue	UBERON:0001013	65.21	gold quality
coronary artery	UBERON:0001621	65.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	64.84	gold quality
left lobe of thyroid gland	UBERON:0001120	64.53	gold quality
left adrenal gland cortex	UBERON:0035825	64.37	gold quality
left adrenal gland	UBERON:0001234	64.13	gold quality
apex of heart	UBERON:0002098	64.13	gold quality
connective tissue	UBERON:0002384	64.08	gold quality
right adrenal gland	UBERON:0001233	63.99	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	2632.62
E-MTAB-6701	yes	43.59
E-HCAD-24	no	790.40
E-HCAD-38	no	174.38
E-ANND-3	no	2.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, BCL6, GATA2, GATA3, JUND, NFKB, NR4A1, PAX1, RELA, SP1, SP3, STAT5B, TFAP2A

miRNA regulators (miRDB)

6 targeting HSD17B1, 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-6832-5P	99.58	64.82	1132
HSA-MIR-3674	97.01	68.86	1171
HSA-MIR-4794	96.47	65.53	1063
HSA-MIR-664A-5P	95.84	64.93	949
HSA-MIR-3178	89.40	60.05	100
HSA-MIR-6784-5P	84.56	60.91	126

Literature-anchored findings (GeneRIF, showing 40)

• increased activity in hypothalamic obesity (PMID:12519880)
• possible hypothalamic mediators regulating adipose tissue 11 beta-HSD-1 might include down-regulation by CRH, ACTH, and alpha 2 sympathetic stimulation, and up-regulation by beta 2 sympathetic stimulation and by the cytokines TNFalpha and IL-1 beta (PMID:12519881)
• examination of amplification in breast cancer (PMID:12527905)
• Evidence for association between the Ser312Gly polymorphism in HSD17B1 and endometriosis was found in a Japanese population (PMID:15640252)
• the germline variants in HSD17B1 characterized by htSNPs do not substantially influence the risk of prostate cancer in U.S. and European whites (PMID:16311626)
• Corticotrophin-releasing hormone (CRH) increased whereas alpha-helical CRH decreased the mRNA levels of STS, CYP19A1, and HSD17B1, the key enzymes for estrogen synthesis. (PMID:16467490)
• HSD17B1 is a multispecific enzyme. (PMID:16480815)
• importance of 17HSD type 2 in breast cancer- & non-tumour breast cell lines; high or low expression affected oestradiol concentration significantly; response dependent on endogenous expression of 17HSD type 1 which seems to be dominant to 17HSD type 2 (PMID:16954436)
• These results suggest that soy consumption may interact with polymorphisms in the 17beta-HSD1 gene in relation to endometrial cancer risk. (PMID:17301695)
• 17beta-hydroxysteroid dehydrogenase type 1 was significantly upregulated in ovarian tissue of patients with ovarian endometriosis. (PMID:17454161)
• ER-positive patients with amplification of HSD17B1 showed lower breast cancer survival than patients without amplification (PMID:17457667)
• Data reported that a higher level of 17beta-hydroxysteroid dehydrogenase type 1mRNA was found in Polycystic Ovary Syndrome compared with the control tissues. (PMID:17953976)
• resequencing analysis does not support the existence of deleterious, gain-of-function or transcription mutations in HSD17B1, which could explain the clustering of breast cancer cases in non-BRCA1/2 high-risk French Canadian families (PMID:18083510)
• The ratio between the mRNA from 17beta-HSD type 1/type 2 was higher in polycystic ovarian syndrome endometria without treatment, whereas, a diminution in the 17beta-HSD type 2 activity was observed. (PMID:18467089)
• HSD17B1 polymorphism is not associated with the risk of breast cancer or fibrocystic breast disease in Chinese women. (PMID:18483327)
• The activity levels of 17beta-hydroxysteroid dehydrogenase (17beta-HSD), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD/3-KSR) and estrone sulfatase in ovarian epithelial carcinomas, were assayed. (PMID:18723074)
• The involvement of aromatase, steroid sulfatase (STS) and reductive 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) in the production of estrogens was determined in four cell lines of endometrial cancer and one cell line of cervix cancer. (PMID:18817841)
• It does not appear that common genetic variation in HSD17B1 is associated with a moderate modulation in breast cancer risk overall. (PMID:18843021)
• Higher mRNA levels of enzymes synthesizing and inactivating androgens are found in differentiated adipocytes, consistent with higher androgen-processing rates in these cells. (PMID:18984855)
• 11beta-HSD-1 gene expression regulation in subcutaneous fat is a consequence rather than cause of adiposity. (PMID:19050176)
• Abnormal increase in the fetal expression of HSD17B1 could contribute to the development of hormonal imbalances, and so result in female masculinization. (PMID:19061935)
• Data suggest that the 17HSD1/17HSD2 ratio might be useful as a predictive factor for tamoxifen treatment in ER-positive breast cancer patients. (PMID:19401349)
• determined the activity and expression levels of known estrogenic 17beta-HSDs, namely types 1, 7 and 12 17beta-HSD in preadipocytes before and after differentiation into mature adipocytes (PMID:19429442)
• 17betaHSD1 inhibitors selectively prevented stimulation of cell proliferation evoked by E1-treatment (PMID:19429452)
• equilibrium E1/E2 ratio maintained by human 17betaHSD1 in intact cells is governed by NADPH saturation, which is strongly dependent on both R38 and high intracellular NADPH/NADP(+) ratios. (PMID:19556422)
• Data report structures of the binary and ternary complexes of 17beta-HSD1 with a new inhibitor E2B, opening a new orientation of breast cancer treatment. (PMID:19929851)
• A significant increment of 17beta-HSD1 followed exemestane neoadjuvant therapy of postmenopausal ER-positive breast carcinoma. This may represent the compensatory response of breast carcinoma tissues to estrogen depletion. (PMID:20151319)
• This study suggests that HSD17B1 312Gly allele may be a protective factor for breast cancer development in Caucasians. (PMID:20151320)
• 17beta-HSD1 up-regulates breast cancer cell growth by a dual action on estradiol synthesis and dihydrotestosterone inactivation. (PMID:20172961)
• CYP17 (T1931C) and HSD17beta1 (A1954G) polymorphisms may jointly increase the risk of breast cancer. (PMID:20193327)
• An amino acid important for steroid/retinoid discrimination was identified and its significance was highlighted by the results of molecular modeling studies. (PMID:20382160)
• genetic assiciation studies [Japan, Brazil]: data suggest SNP in 17beta-HSD1 gene may modify association between dietary isoflavone intake & breast cancer (PMID:20432167)
• Genetic variants in ESR1, ESR2, and HSD17B1 genes could modify susceptibility to endometriosis and might influence the fertility status in endometriosis patients. (PMID:20586553)
• Obese women with selected CYP19 and 17-beta HSD gene variants had remarkably different E2 trajectories around the the final menstrual period, resulting in different postmenopausal E2 levels. (PMID:21198743)
• HSD17B1 gene may contribute to sex steroid-mediated effects on colorectal cancer development. (PMID:21317201)
• HSD17B1 upregulation by sodium butyrate is associated with increased conversion of E1 to E2 in colorectal cancer cells. (PMID:21563966)
• Data show that in 17beta-HSD1 inhibitors are placed in the substrate-binding site and they occupy an apolar subpocket consisting of the following amino acids: Gly94, Leu95, Leu96, Asn152, Tyr155, and Phe192. (PMID:21857977)
• reduced HSD17B1 expression can be associated with DNA methylation in the 5’ flanking region of HSD17B1 in CRC from the proximal colon. (PMID:22176788)
• SNPs (HSD17B1 (rs2010750, rs598126 and rs676387), COMT (rs4680), UGT1A1 (rs8175347) and ESR1 (rs9340799)) seem to be related to mammographic density in the same direction of their associations with breast cancer risk (PMID:22199302)
• Breast cancer cells T47D, MCF-7, BT 20, and JEG 3 as control cells, were chosen to evaluate the contribution of 17beta-hydroxysteroid dehydrogenase type 1 and type 2 to the estradiol/estrone ratio. (PMID:22253796)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hsd17b1	ENSDARG00000027469
mus_musculus	Hsd17b1	ENSMUSG00000019301
rattus_norvegicus	Hsd17b1	ENSRNOG00000019830

Paralogs (25): HSD17B6 (ENSG00000025423), RDH11 (ENSG00000072042), HSD17B10 (ENSG00000072506), DHRS9 (ENSG00000073737), HSD17B2 (ENSG00000086696), HSD17B14 (ENSG00000087076), DHRS12 (ENSG00000102796), HSDL1 (ENSG00000103160), RDH10 (ENSG00000121039), HSD17B3 (ENSG00000130948), HSD17B7 (ENSG00000132196), HSD17B4 (ENSG00000133835), RDH5 (ENSG00000135437), RDH16 (ENSG00000139547), RDH12 (ENSG00000139988), HSD17B12 (ENSG00000149084), BDH1 (ENSG00000161267), DHRS3 (ENSG00000162496), SDR9C7 (ENSG00000170426), HSD17B13 (ENSG00000170509), SDR16C5 (ENSG00000170786), HSD11B2 (ENSG00000176387), WWOX (ENSG00000186153), HSD17B11 (ENSG00000198189), HSD17B8 (ENSG00000204228)

Protein

Protein identifiers

17-beta-hydroxysteroid dehydrogenase type 1 — P14061 (reviewed: P14061)

Alternative names: 20 alpha-hydroxysteroid dehydrogenase, E2DH, Estradiol 17-beta-dehydrogenase 1, Placental 17-beta-hydroxysteroid dehydrogenase, Short chain dehydrogenase/reductase family 28C member 1

All UniProt accessions (3): P14061, A0A0A0MQS7, B4DU11

UniProt curated annotations — full annotation on UniProt →

Function. Favors the reduction of estrogens and androgens. Converts estrone (E1) to a more potent estrogen, 17beta-estradiol (E2). Also has 20-alpha-HSD activity. Uses preferentially NADH.

Subunit / interactions. Homodimer. Exists predominantly as a homodimer but also exits as monomer.

Subcellular location. Cytoplasm.

Pathway. Steroid biosynthesis; estrogen biosynthesis.

Similarity. Belongs to the short-chain dehydrogenases/reductases (SDR) family.

RefSeq proteins (2): NP_000404, NP_001317148 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR011348	17beta_DH	Family
IPR020904	Sc_DH/Rdtase_CS	Conserved_site
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF00106

Enzyme classification (BRENDA):

• EC 1.1.1.51 — 3(or 17)beta-hydroxysteroid dehydrogenase (BRENDA: 18 organisms, 150 substrates, 207 inhibitors, 72 Km, 42 kcat entries)
• EC 1.1.1.62 — 17beta-estradiol 17-dehydrogenase (BRENDA: 20 organisms, 283 substrates, 790 inhibitors, 95 Km, 44 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ESTRADIOL-17BETA	0.0008–0.025	14
ESTRONE	—	10
NADP+	0.0001–9	9
TESTOSTERONE	0.0006–0.31	7
17BETA-ESTRADIOL	0.0006–0.082	7
NADPH	0.0003–0.16	7
ESTRADIOL	0.0036–0.118	6
NAD+	0.023–0.26	5
NADH	0.0053–0.642	4
NADP+	0.0082–9.6	4
TESTOSTERONE	0.0071–0.263	4
5ALPHA-ANDROST-16-EN-3-ONE	0.068–0.176	3
5ALPHA-DIHYDROTESTOSTERONE	0.0076–0.2	3
DEHYDROEPIANDROSTERONE	0.0172–0.0598	3
5ALPHA-PREGNAN-3BETA-OL-20-ONE	0.0039–0.116	2

Catalyzed reactions (Rhea), 3 shown:

• testosterone + NADP(+) = androst-4-ene-3,17-dione + NADPH + H(+) (RHEA:14981)
• 17beta-estradiol + NAD(+) = estrone + NADH + H(+) (RHEA:24612)
• 17beta-estradiol + NADP(+) = estrone + NADPH + H(+) (RHEA:24616)

UniProt features (47 total): helix 15, mutagenesis site 10, strand 9, binding site 4, sequence variant 2, initiator methionine 1, chain 1, region of interest 1, sequence conflict 1, active site 1, turn 1, modified residue 1

Structure

Experimental structures (PDB)

28 structures.

PDB	Method	Resolution (Å)
1JTV	X-RAY DIFFRACTION	1.54
1I5R	X-RAY DIFFRACTION	1.6
1QYW	X-RAY DIFFRACTION	1.63
1FDS	X-RAY DIFFRACTION	1.7
3DEY	X-RAY DIFFRACTION	1.7
3KLM	X-RAY DIFFRACTION	1.7
1QYV	X-RAY DIFFRACTION	1.81
6MNE	X-RAY DIFFRACTION	1.86
1QYX	X-RAY DIFFRACTION	1.89
1A27	X-RAY DIFFRACTION	1.9
3HB5	X-RAY DIFFRACTION	2
6DTP	X-RAY DIFFRACTION	2
6CGC	X-RAY DIFFRACTION	2.1
1BHS	X-RAY DIFFRACTION	2.2
1FDT	X-RAY DIFFRACTION	2.2
6CGE	X-RAY DIFFRACTION	2.2
3HB4	X-RAY DIFFRACTION	2.21
1DHT	X-RAY DIFFRACTION	2.24
7X3Z	X-RAY DIFFRACTION	2.25
1IOL	X-RAY DIFFRACTION	2.3
3DHE	X-RAY DIFFRACTION	2.3
3KM0	X-RAY DIFFRACTION	2.3
6MNC	X-RAY DIFFRACTION	2.4
3KLP	X-RAY DIFFRACTION	2.5
1FDU	X-RAY DIFFRACTION	2.7
1FDW	X-RAY DIFFRACTION	2.7
1EQU	X-RAY DIFFRACTION	3
1FDV	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14061-F1	91.05	0.85

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 (1): 156 (proton acceptor)

Ligand- & substrate-binding residues (4): 10–38; 66; 143; 160

Post-translational modifications (1): 135

Mutagenesis-validated functional residues (10):

Position	Phenotype
112–114	loss of 17-beta-hydroxysteroid dehydrogenase activity.
135	abolishes phosphorylation. no effect on 17-beta-hydroxysteroid dehydrogenase activity.
143	loss of 17-beta-hydroxysteroid dehydrogenase activity.
150	alters substrate specificity.
156	loss of 17-beta-hydroxysteroid dehydrogenase activity.
160	loss of 17-beta-hydroxysteroid dehydrogenase activity.
171	loss of 17-beta-hydroxysteroid dehydrogenase activity.
222	no effect on conversion of estrone to 17beta-estradiol.
283	no effect on conversion of estrone to 17beta-estradiol.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-193144	Estrogen biosynthesis
R-HSA-2453902	The canonical retinoid cycle in rods (twilight vision)

MSigDB gene sets: 148 (showing top): GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_VACUOLE_ORGANIZATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_HORMONE_LEVELS, GGGTGGRR_PAX4_03, GOBP_KETONE_METABOLIC_PROCESS, GOBP_RESPONSE_TO_METAL_ION, GOMF_STEROID_DEHYDROGENASE_ACTIVITY_ACTING_ON_THE_CH_OH_GROUP_OF_DONORS_NAD_OR_NADP_AS_ACCEPTOR, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, RICKMAN_METASTASIS_DN, GOBP_BONE_DEVELOPMENT, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, MODULE_379

GO Biological Process (11): estrogen biosynthetic process (GO:0006703), lysosome organization (GO:0007040), skeletal muscle tissue development (GO:0007519), gene expression (GO:0010467), bone development (GO:0060348), adipose tissue development (GO:0060612), testosterone biosynthetic process (GO:0061370), cellular response to metal ion (GO:0071248), lipid metabolic process (GO:0006629), steroid biosynthetic process (GO:0006694), estrogen metabolic process (GO:0008210)

GO Molecular Function (14): estradiol 17-beta-dehydrogenase [NAD(P)+] activity (GO:0004303), steroid binding (GO:0005496), small molecule binding (GO:0036094), protein homodimerization activity (GO:0042803), testosterone dehydrogenase (NAD+) activity (GO:0047035), testosterone dehydrogenase (NADP+) activity (GO:0047045), NADP binding (GO:0050661), NADP+ binding (GO:0070401), 17-beta-hydroxysteroid dehydrogenase (NADP+) activity (GO:0072582), estradiol binding (GO:1903924), catalytic activity (GO:0003824), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), obsolete testosterone dehydrogenase [NAD(P)+] activity (GO:0030283)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of steroid hormones	1
Visual phototransduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	2
steroid metabolic process	2
steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	2
binding	2
cellular anatomical structure	2
estrogen metabolic process	1
hormone biosynthetic process	1
steroid hormone biosynthetic process	1
lytic vacuole organization	1
striated muscle tissue development	1
skeletal muscle organ development	1
macromolecule biosynthetic process	1
skeletal system development	1
connective tissue development	1
steroid biosynthetic process	1
ketone biosynthetic process	1
olefinic compound biosynthetic process	1
response to metal ion	1
cellular response to chemical stimulus	1
primary metabolic process	1
lipid biosynthetic process	1
hormone metabolic process	1
lipid binding	1
identical protein binding	1
protein dimerization activity	1
17-beta-hydroxysteroid dehydrogenase (NAD+) activity	1
17-beta-hydroxysteroid dehydrogenase (NADP+) activity	1
adenyl nucleotide binding	1
anion binding	1
NADP binding	1
steroid binding	1
molecular_function	1
catalytic activity	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3615 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSD17B1	HSD17B2	P37059	986
HSD17B1	HSD17B3	P37058	976
HSD17B1	DHRS11	Q6UWP2	964
HSD17B1	HSD17B4	P51659	928
HSD17B1	HSD17B7	P56937	918
HSD17B1	HSD3B1	P14060	876
HSD17B1	CYP17A1	P05093	822
HSD17B1	CYP19A1	P11511	822
HSD17B1	CYP11A1	P05108	801
HSD17B1	NAGLU	P54802	763
HSD17B1	STS	P08842	736
HSD17B1	AKR1C3	P42330	729
HSD17B1	MLX	Q9UH92	725
HSD17B1	MLXIP	Q9HAP2	715
HSD17B1	TRMT10C	Q7L0Y3	692

IntAct

7 interactions, top by confidence:

A	B	Type	Score
ALOX5	HSD17B1	psi-mi:“MI:0915”(physical association)	0.560
APBA3	HSD17B1	psi-mi:“MI:0915”(physical association)	0.370
HSD17B1	RAD21	psi-mi:“MI:0914”(association)	0.350
IL5RA	C4A	psi-mi:“MI:0914”(association)	0.350
ALOX5	HSD17B1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): HSD17B1 (Reconstituted Complex), HSD17B1 (Two-hybrid), HSD17B1 (Co-crystal Structure), HSD17B1 (Affinity Capture-RNA), MPZL1 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), RNASEL (Affinity Capture-MS), MCU (Affinity Capture-MS), RAB3B (Affinity Capture-MS), HMOX1 (Affinity Capture-MS), PDLIM5 (Affinity Capture-MS), AFAP1L1 (Affinity Capture-MS), HSD17B1 (Affinity Capture-MS), CCRN4L (Affinity Capture-MS), RAD21 (Affinity Capture-MS)

ESM2 similar proteins: A0A0H3KNE7, A0A3Q8GL18, A0A3Q8GLE8, A0A3Q8GYY4, A0A7N9VSG0, A0A7T8F1N2, A0A8F5XX49, A0A8I6GJ95, A0AAT9JA24, A5W4G5, A8C7R7, B8A5W4, D4A2B7, E9Q3D4, E9QUT3, G4N290, O35048, P0C622, P14061, P23102, P37440, P51656, P51661, P9WES5, P9WGQ2, P9WGQ3, Q08632, Q13268, Q17QU7, Q17QW3, Q4WR19, Q5C9I9, Q5R9W5, Q5SS80, Q7FAE1, Q7ZY31, Q8SPU8, Q8VBZ0, Q8XBJ4, Q91WL8

Diamond homologs: A0A017SE81, A0A0E3D8L9, A0A0U1LQE2, A0A140JWS5, A0A1U8QWA2, A0A5B8YU68, A0QYC2, A7IQF2, C0KTJ6, G0RH19, G4N286, G9N4A9, O16881, O55240, P05406, P0CU71, P0DKC7, P14061, P25970, P35731, P37694, P37959, P40471, P42317, P43713, P45200, P45375, P50160, P50203, P51658, P54554, P55006, P55336, P80873, Q04520, Q09851, Q0IH28, Q0VFE7, Q1QU27, Q1R183

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
HSD17B1	“up-regulates quantity”	estrone	“chemical modification”
HSD17B1	“up-regulates quantity”	17beta-estradiol	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

797 predictions. Top by Δscore:

Variant	Effect	Δscore
17:42553122:A:AG	acceptor_gain	1.0000
17:42553123:G:GA	acceptor_gain	1.0000
17:42553123:GT:G	acceptor_gain	1.0000
17:42553123:GTGT:G	acceptor_gain	1.0000
17:42553437:A:AG	acceptor_gain	1.0000
17:42553438:G:GA	acceptor_gain	1.0000
17:42553617:GG:G	donor_gain	1.0000
17:42553618:GG:G	donor_gain	1.0000
17:42554395:C:CA	acceptor_gain	1.0000
17:42554403:A:AG	acceptor_gain	1.0000
17:42554404:G:GG	acceptor_gain	1.0000
17:42554404:GCTT:G	acceptor_gain	1.0000
17:42554571:G:GT	donor_gain	1.0000
17:42554578:CGGAG:C	donor_loss	1.0000
17:42554580:GAGG:G	donor_loss	1.0000
17:42554581:AGGTG:A	donor_loss	1.0000
17:42554582:GGTG:G	donor_loss	1.0000
17:42554583:GTGA:G	donor_loss	1.0000
17:42554584:T:A	donor_loss	1.0000
17:42552925:A:AG	acceptor_gain	0.9900
17:42552926:G:GA	acceptor_gain	0.9900
17:42553113:A:AG	acceptor_gain	0.9900
17:42553116:A:G	acceptor_gain	0.9900
17:42553117:C:G	acceptor_gain	0.9900
17:42553122:AGT:A	acceptor_gain	0.9900
17:42553123:GTG:G	acceptor_gain	0.9900
17:42553289:TGGGT:T	donor_loss	0.9900
17:42553292:G:GA	donor_loss	0.9900
17:42553292:G:GG	donor_gain	0.9900
17:42553293:TGA:T	donor_loss	0.9900

AlphaMissense

2089 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:42553823:A:C	S159R	0.994
17:42553825:C:A	S159R	0.994
17:42553825:C:G	S159R	0.994
17:42553829:T:C	F161L	0.994
17:42553831:C:A	F161L	0.994
17:42553831:C:G	F161L	0.994
17:42553600:A:C	S143R	0.991
17:42553602:C:A	S143R	0.991
17:42553602:C:G	S143R	0.991
17:42553824:G:T	S159I	0.987
17:42553802:T:C	F152L	0.986
17:42553804:C:A	F152L	0.986
17:42553804:C:G	F152L	0.986
17:42553853:A:C	S169R	0.983
17:42553855:T:A	S169R	0.983
17:42553855:T:G	S169R	0.983
17:42552966:T:G	C11W	0.982
17:42553130:C:A	A35D	0.982
17:42553566:G:C	K131N	0.981
17:42553566:G:T	K131N	0.981
17:42553618:G:T	G149W	0.978
17:42553819:C:G	C157W	0.976
17:42553821:C:A	A158D	0.974
17:42554409:A:C	S182R	0.974
17:42554411:C:A	S182R	0.974
17:42554411:C:G	S182R	0.974
17:42554437:C:T	T191I	0.974
17:42553802:T:A	F152I	0.973
17:42553518:T:A	N115K	0.971
17:42553518:T:G	N115K	0.971

dbSNP variants (sampled 300 via entrez): RS1000027727 (17:42553972 G>A), RS1000409159 (17:42551317 T>C), RS1002344676 (17:42551178 T>A,C,G), RS1002850516 (17:42555396 A>G), RS1003758694 (17:42553696 G>C,T), RS1006683899 (17:42554912 G>C), RS1007097468 (17:42551939 T>A), RS1007393905 (17:42551768 A>T), RS1008917306 (17:42551627 G>A), RS1009853491 (17:42551581 C>T), RS1010170737 (17:42551866 G>A), RS1010905496 (17:42551895 T>C), RS1011086433 (17:42553954 TGCGGGAGCC>T), RS1011117656 (17:42554336 G>A), RS1012071135 (17:42555049 G>A)

Disease associations

OMIM: gene MIM:109684 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003984_19	Parkinson’s disease	7.000000e-08
GCST004278_32	Pulse pressure	3.000000e-09
GCST004278_41	Pulse pressure	6.000000e-08
GCST004278_63	Pulse pressure	3.000000e-09
GCST004278_71	Pulse pressure	4.000000e-07
GCST007269_304	Pulse pressure	5.000000e-14
GCST009718_5	Eczema	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3181 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 106,874 (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
CHEMBL1405	ESTRONE	4	36,722
CHEMBL44	GENISTEIN	2	44,212
CHEMBL150	KAEMPFEROL	1	25,940

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

Binding affinities (BindingDB)

38 measured of 61 human assays (61 total across all organisms); most potent 38 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-methoxy-5-(6-methoxynaphthalen-2-yl)-N-phenylbenzamide	IC50	7 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
N-[2-methoxy-4-(6-methoxynaphthalen-2-yl)phenyl]acetamide	IC50	10 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
6-(3-hydroxyphenyl)-1-(4-morpholin-4-ylphenyl)naphthalen-2-ol	IC50	20 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
4-[4-[2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl]anilino]-4-oxobutanoic acid	IC50	20 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
N-[3-[2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl]phenyl]methanesulfonamide	IC50	23 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
(E)-3-[3-methoxy-5-(6-methoxynaphthalen-2-yl)phenyl]-N-methylprop-2-enamide	IC50	30 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
US8546392, 68	IC50	39 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
N-[3-[2-hydroxy-6-(3-hydroxyphenyl)naphthalen-1-yl]phenyl]acetamide	IC50	40 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
3-[3-methoxy-5-(6-methoxynaphthalen-2-yl)phenyl]-N-methylpropanamide	IC50	50 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
3-methoxy-5-(6-methoxynaphthalen-2-yl)-N-methylbenzamide	IC50	50 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
4-[2-(3-hydroxyphenyl)-1,3-thiazol-5-yl]phenol	IC50	50 nM
EM1745	IC50	52 nM
(E)-3-[3-methoxy-5-(6-methoxynaphthalen-2-yl)phenyl]-N-phenylprop-2-enamide	IC50	60 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
3-[5-(4-hydroxyphenyl)thiophen-2-yl]phenol	IC50	69 nM
ethyl (E)-3-[2-methoxy-6-(3-methoxyphenyl)naphthalen-1-yl]prop-2-enoate	IC50	70 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
3-[4-(4-hydroxyphenyl)thiophen-2-yl]phenol	IC50	77 nM
3-[2-methoxy-6-(3-methoxyphenyl)naphthalen-1-yl]-N-(1,3-thiazol-2-yl)benzenesulfonamide	IC50	90 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
[5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl 8-[(1S,10R,11S,14S,15S)-5,14-dihydroxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2,4,6-trien-13-yl]octanoate	IC50	93 nM
3-[5-(3-hydroxyphenyl)pyridin-2-yl]phenol	IC50	101 nM
3-methoxy-7-(3-methoxyphenyl)-N-methylnaphthalene-2-carboxamide	IC50	114 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
3-[3-methoxy-5-(6-methoxynaphthalen-2-yl)phenyl]-N-phenylpropanamide	IC50	140 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
[5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl 10-[(1S,10R,11S,14S,15S)-5,14-dihydroxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2,4,6-trien-13-yl]decanoate	IC50	140 nM
4-[4-(3-hydroxyphenyl)thiophen-2-yl]phenol	IC50	151 nM
3-[5-(3-hydroxyphenyl)-1,2,4-thiadiazol-3-yl]phenol	IC50	169 nM
3-[5-(3-hydroxyphenyl)thiophen-2-yl]phenol	IC50	173 nM
3-[4-(3-hydroxyphenyl)phenyl]phenol	IC50	173 nM
3-[4-(3-hydroxyphenyl)thiophen-2-yl]phenol	IC50	185 nM
cid_269792	IC50	201 nM
3-[2-(3-hydroxyphenyl)-1,3-thiazol-5-yl]phenol	IC50	243 nM
3-[5-(3-hydroxyphenyl)-1,3,4-thiadiazol-2-yl]phenol	IC50	336 nM
3-(5-phenylthiophen-2-yl)phenol	IC50	342 nM
4-[5-(3-hydroxyphenyl)-1,2,4-thiadiazol-3-yl]phenol	IC50	413 nM
3-[2-(3-hydroxyphenyl)-1,3-thiazol-4-yl]phenol	IC50	455 nM
3-[4-(4-hydroxyphenyl)phenyl]phenol	IC50	471 nM
2-methoxy-6-[3-methoxy-5-(6-methoxynaphthalen-2-yl)phenyl]naphthalene	IC50	500 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
6-(3-hydroxyphenyl)-1-(6-methoxy-3-pyridinyl)naphthalen-2-ol	IC50	840 nM	US-8546392: 17Beta-hydroxysteroid dehydrogenase type 1 inhibitors for the treatment of hormone-related diseases
3-[5-(3-hydroxyphenyl)pyrazin-2-yl]phenol	IC50	1000 nM
[5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl nonanoate	KI	250000 nM

ChEMBL bioactivities

722 potent at pChembl≥5 of 789 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL4457145
10.00	IC50	0.1	nM	CHEMBL4529443
9.70	IC50	0.2	nM	CHEMBL4063985
9.52	IC50	0.3	nM	CHEMBL4103524
9.40	IC50	0.4	nM	CHEMBL4101264
9.40	IC50	0.4	nM	CHEMBL4283851
9.30	IC50	0.5	nM	CHEMBL4063839
9.30	IC50	0.5	nM	CHEMBL4079675
9.30	IC50	0.5	nM	CHEMBL4454887
9.22	IC50	0.6	nM	CHEMBL4466918
9.15	IC50	0.7	nM	CHEMBL4546082
9.10	IC50	0.8	nM	CHEMBL4464314
9.05	IC50	0.9	nM	CHEMBL4077264
9.05	IC50	0.9	nM	CHEMBL4286251
8.96	IC50	1.1	nM	CHEMBL4071245
8.92	IC50	1.2	nM	CHEMBL4099360
8.92	IC50	1.2	nM	CHEMBL4290218
8.92	IC50	1.2	nM	CHEMBL4441152
8.89	IC50	1.3	nM	CHEMBL4062959
8.85	IC50	1.4	nM	CHEMBL4062685
8.85	IC50	1.4	nM	CHEMBL4072794
8.85	IC50	1.4	nM	CHEMBL4582194
8.82	IC50	1.5	nM	CHEMBL4287575
8.77	IC50	1.7	nM	CHEMBL4291714
8.77	IC50	1.7	nM	CHEMBL4538007
8.70	IC50	2	nM	CHEMBL3629585
8.70	IC50	2	nM	CHEMBL3629587
8.70	IC50	2	nM	CHEMBL3629590
8.70	IC50	2	nM	CHEMBL4585585
8.68	IC50	2.1	nM	CHEMBL4060257
8.68	IC50	2.1	nM	CHEMBL4082298
8.66	IC50	2.2	nM	CHEMBL4078356
8.66	IC50	2.2	nM	CHEMBL373257
8.64	IC50	2.3	nM	CHEMBL4443578
8.62	IC50	2.4	nM	CHEMBL4091749
8.62	IC50	2.4	nM	CHEMBL4450585
8.60	IC50	2.5	nM	CHEMBL4102153
8.57	IC50	2.7	nM	CHEMBL4099681
8.57	IC50	2.7	nM	CHEMBL5089787
8.54	IC50	2.9	nM	CHEMBL5090458
8.54	IC50	2.9	nM	CHEMBL5080299
8.52	IC50	3	nM	CHEMBL3629586
8.52	IC50	3	nM	CHEMBL4071588
8.52	IC50	3	nM	CHEMBL4537350
8.52	Ki	3	nM	CHEMBL371948
8.52	Ki	3	nM	ESTRONE
8.51	IC50	3.1	nM	CHEMBL4071588
8.51	IC50	3.1	nM	CHEMBL4286141
8.51	IC50	3.1	nM	CHEMBL4576023
8.49	IC50	3.2	nM	CHEMBL5440157

PubChem BioAssay actives

688 with measured affinity, of 2113 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
4-methyl-N-[3-[5-(2,4,5-trifluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]benzenesulfonamide	1601560: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis	ic50	0.0001	uM
3-methyl-N-[3-[5-(2,4,5-trifluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]benzenesulfonamide	1601560: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis	ic50	0.0001	uM
[5-(3-chloro-4-hydroxy-5-methylphenyl)thiophen-2-yl]-(2,6-difluoro-3-hydroxyphenyl)methanone	1428181: Inhibition of human placental cytosolic 17beta-HSD1 assessed as reduction in activation of [2,4,6,7-3H]-E1 substrate to E2 after 10 mins in presence of NADH by RP-HPLC method	ic50	0.0002	uM
[5-(3-chloro-4-methoxy-5-methylphenyl)thiophen-2-yl]-(2,6-difluoro-3-hydroxyphenyl)methanone	1428181: Inhibition of human placental cytosolic 17beta-HSD1 assessed as reduction in activation of [2,4,6,7-3H]-E1 substrate to E2 after 10 mins in presence of NADH by RP-HPLC method	ic50	0.0003	uM
[5-(3,5-dichloro-4-methoxyphenyl)thiophen-2-yl]-(2,4,5-trifluoro-3-hydroxyphenyl)methanone	1415114: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1 as substrate after 10 mins in presence of NADPH by radio-flow detector based analysis	ic50	0.0004	uM
(2,6-difluoro-3-hydroxyphenyl)-[5-(4-hydroxy-3,5-dimethylphenyl)thiophen-2-yl]methanone	1428181: Inhibition of human placental cytosolic 17beta-HSD1 assessed as reduction in activation of [2,4,6,7-3H]-E1 substrate to E2 after 10 mins in presence of NADH by RP-HPLC method	ic50	0.0004	uM
(6-chloro-2-fluoro-3-hydroxyphenyl)-[5-(3,5-dichloro-4-methoxyphenyl)thiophen-2-yl]methanone	1566789: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis	ic50	0.0005	uM
[5-(3,5-dichloro-4-methoxyphenyl)thiophen-2-yl]-(2,6-difluoro-3-hydroxyphenyl)methanone	1428181: Inhibition of human placental cytosolic 17beta-HSD1 assessed as reduction in activation of [2,4,6,7-3H]-E1 substrate to E2 after 10 mins in presence of NADH by RP-HPLC method	ic50	0.0005	uM
[5-(3-chloro-4-hydroxyphenyl)thiophen-2-yl]-(2,6-difluoro-3-hydroxyphenyl)methanone	1428181: Inhibition of human placental cytosolic 17beta-HSD1 assessed as reduction in activation of [2,4,6,7-3H]-E1 substrate to E2 after 10 mins in presence of NADH by RP-HPLC method	ic50	0.0005	uM
2-cyano-N-[3-[5-(2,4,5-trifluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]benzenesulfonamide	1564135: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis	ic50	0.0006	uM
4-chloro-N-[3-[5-(2,4,5-trifluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]benzenesulfonamide	1601560: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis	ic50	0.0007	uM
3-chloro-N-[3-[5-(2,4,5-trifluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]benzenesulfonamide	1601560: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis	ic50	0.0008	uM
[5-(4-hydroxy-3,5-dimethylphenyl)thiophen-2-yl]-(2,4,5-trifluoro-3-hydroxyphenyl)methanone	1415114: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1 as substrate after 10 mins in presence of NADPH by radio-flow detector based analysis	ic50	0.0009	uM
(2,6-difluoro-3-hydroxyphenyl)-[5-(4-methoxy-3,5-dimethylphenyl)thiophen-2-yl]methanone	1428181: Inhibition of human placental cytosolic 17beta-HSD1 assessed as reduction in activation of [2,4,6,7-3H]-E1 substrate to E2 after 10 mins in presence of NADH by RP-HPLC method	ic50	0.0009	uM
[2-chloro-4-[5-(2,6-difluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl] sulfamate	1482688: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1/E1 substrate and NADH after 10 mins by HPLC based radio-detection method	ic50	0.0011	uM
[5-(4-methoxy-3,5-dimethylphenyl)thiophen-2-yl]-(2,4,5-trifluoro-3-hydroxyphenyl)methanone	1415114: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1 as substrate after 10 mins in presence of NADPH by radio-flow detector based analysis	ic50	0.0012	uM
[5-(3-chlorophenyl)thiophen-2-yl]-(2,6-difluoro-3-hydroxyphenyl)methanone	1428181: Inhibition of human placental cytosolic 17beta-HSD1 assessed as reduction in activation of [2,4,6,7-3H]-E1 substrate to E2 after 10 mins in presence of NADH by RP-HPLC method	ic50	0.0012	uM
4-fluoro-N-[3-[5-(2,4,5-trifluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]benzenesulfonamide	1564135: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis	ic50	0.0012	uM
[5-(3-chloro-4-methoxyphenyl)thiophen-2-yl]-(2,6-difluoro-3-hydroxyphenyl)methanone	1428181: Inhibition of human placental cytosolic 17beta-HSD1 assessed as reduction in activation of [2,4,6,7-3H]-E1 substrate to E2 after 10 mins in presence of NADH by RP-HPLC method	ic50	0.0013	uM
1-[4-[[3-chloro-5-[5-(2,6-difluoro-3-hydroxybenzoyl)thiophen-2-yl]-2-methoxyphenyl]methyl]piperazin-1-yl]ethanone	1428181: Inhibition of human placental cytosolic 17beta-HSD1 assessed as reduction in activation of [2,4,6,7-3H]-E1 substrate to E2 after 10 mins in presence of NADH by RP-HPLC method	ic50	0.0014	uM
[2-chloro-4-[5-(2,6-difluoro-3-hydroxybenzoyl)thiophen-2-yl]-3-fluorophenyl] sulfamate	1482688: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1/E1 substrate and NADH after 10 mins by HPLC based radio-detection method	ic50	0.0014	uM
N-[3-[5-(2,6-difluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]benzenesulfonamide	1601560: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis	ic50	0.0014	uM
[5-(1H-indol-4-yl)thiophen-2-yl]-(2,4,5-trifluoro-3-hydroxyphenyl)methanone	1415114: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1 as substrate after 10 mins in presence of NADPH by radio-flow detector based analysis	ic50	0.0015	uM
[5-(3-chloro-4-hydroxyphenyl)thiophen-2-yl]-(2,4,5-trifluoro-3-hydroxyphenyl)methanone	1415114: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1 as substrate after 10 mins in presence of NADPH by radio-flow detector based analysis	ic50	0.0017	uM
N-[3-[5-(6-chloro-2-fluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]benzenesulfonamide	1601560: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis	ic50	0.0017	uM
4-bromo-N-[3-[5-(2,6-difluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]-2-(trifluoromethoxy)benzenesulfonamide	1252528: Inhibition of human placental cytosolic 17beta HSD1 using unlabeled- and labelled [2,4,6,7-3H]-E1 as substrate incubated for 10 mins by HPLC analysis	ic50	0.0020	uM
N-[3-[5-(2,6-difluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]-2-(trifluoromethyl)benzenesulfonamide	1252528: Inhibition of human placental cytosolic 17beta HSD1 using unlabeled- and labelled [2,4,6,7-3H]-E1 as substrate incubated for 10 mins by HPLC analysis	ic50	0.0020	uM
N-[3-[5-(2,6-difluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]cyclopropanesulfonamide	1252528: Inhibition of human placental cytosolic 17beta HSD1 using unlabeled- and labelled [2,4,6,7-3H]-E1 as substrate incubated for 10 mins by HPLC analysis	ic50	0.0020	uM
4-fluoro-N-[2-methyl-5-[5-(2,4,5-trifluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]benzenesulfonamide	1564135: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis	ic50	0.0020	uM
1-[4-[[3-chloro-5-[5-(2,6-difluoro-3-hydroxybenzoyl)thiophen-2-yl]-2-hydroxyphenyl]methyl]piperazin-1-yl]ethanone	1428181: Inhibition of human placental cytosolic 17beta-HSD1 assessed as reduction in activation of [2,4,6,7-3H]-E1 substrate to E2 after 10 mins in presence of NADH by RP-HPLC method	ic50	0.0021	uM
[5-[3-chloro-4-methoxy-5-(triazol-1-ylmethyl)phenyl]thiophen-2-yl]-(2,6-difluoro-3-hydroxyphenyl)methanone	1428181: Inhibition of human placental cytosolic 17beta-HSD1 assessed as reduction in activation of [2,4,6,7-3H]-E1 substrate to E2 after 10 mins in presence of NADH by RP-HPLC method	ic50	0.0021	uM
3-(4-fluorophenyl)-5-[4-[4-methyl-5-[2-(trifluoromethyl)phenyl]-1,2,4-triazol-3-yl]-1-bicyclo[2.2.2]octanyl]-1,2,4-oxadiazole	366733: Inhibition of human 11beta-HSD1	ic50	0.0022	uM
[3-[5-(2,6-difluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl] sulfamate	1482688: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1/E1 substrate and NADH after 10 mins by HPLC based radio-detection method	ic50	0.0022	uM
4-fluoro-N-[2-fluoro-5-[5-(2,4,5-trifluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]benzenesulfonamide	1564135: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis	ic50	0.0023	uM
4-bromo-N-[3-[5-(2,4,5-trifluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]-2-(trifluoromethoxy)benzenesulfonamide	1601560: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis	ic50	0.0024	uM
[5-(3,5-dichloro-4-hydroxyphenyl)thiophen-2-yl]-(2,6-difluoro-3-hydroxyphenyl)methanone	1428181: Inhibition of human placental cytosolic 17beta-HSD1 assessed as reduction in activation of [2,4,6,7-3H]-E1 substrate to E2 after 10 mins in presence of NADH by RP-HPLC method	ic50	0.0024	uM
[4-[5-(2,6-difluoro-3-hydroxybenzoyl)thiophen-2-yl]-2-fluorophenyl] sulfamate	1482688: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1/E1 substrate and NADH after 10 mins by HPLC based radio-detection method	ic50	0.0025	uM
[4-[5-(2,6-difluoro-3-hydroxybenzoyl)thiophen-2-yl]-2,3-difluorophenyl] sulfamate	1482688: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1/E1 substrate and NADH after 10 mins by HPLC based radio-detection method	ic50	0.0027	uM
5-(3-chloro-4-hydroxyphenyl)-N-methyl-N-(2-methylphenyl)furan-2-carboxamide	1834417: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NADH measured after 10 mins by HPLC method	ic50	0.0027	uM
5-(4-hydroxy-3,5-dimethylphenyl)-N-methyl-N-(2-methylphenyl)furan-2-carboxamide	1981867: Inhibition of human 17beta-HSD1 expressed in human T47D cells using [3H]E1 as substrate incubated for 1 hr followed by substrate addition measured after 40 mins in presence of E1 by HPLC analysis	ic50	0.0029	uM
5-(3,5-dichloro-4-hydroxyphenyl)-N-methyl-N-(2-methylphenyl)furan-2-carboxamide	1834417: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NADH measured after 10 mins by HPLC method	ic50	0.0029	uM
N-[3-[5-(2,6-difluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]-2-(trifluoromethoxy)benzenesulfonamide	1252528: Inhibition of human placental cytosolic 17beta HSD1 using unlabeled- and labelled [2,4,6,7-3H]-E1 as substrate incubated for 10 mins by HPLC analysis	ic50	0.0030	uM
(2,6-difluoro-3-hydroxyphenyl)-[5-(4-hydroxyphenyl)thiophen-2-yl]methanone	1428181: Inhibition of human placental cytosolic 17beta-HSD1 assessed as reduction in activation of [2,4,6,7-3H]-E1 substrate to E2 after 10 mins in presence of NADH by RP-HPLC method	ic50	0.0030	uM
(6-chloro-2-fluoro-3-hydroxyphenyl)-[5-(3,5-dichloro-4-hydroxyphenyl)thiophen-2-yl]methanone	1566789: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis	ic50	0.0030	uM
[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl 9-[(8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-16-yl]nonanoate	1797613: Enzyme Inhibition on the Conversion of E2 to E1 by 17beta-HSD1 from Article 10.1096/fj.02-0026fje: “A concerted, rational design of type 1 17beta-hydroxysteroid dehydrogenase inhibitors: estradiol-adenosine hybrids with high affinity.”	ki	0.0030	uM
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl 9-[(8R,9S,13S,14S,16S,17S)-3,17-dihydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-16-yl]nonanoate	406995: Inhibition of human recombinant 17beta-HSD1 expressed in HEK293 cell lysate assessed as conversion of radiolabeled estrone to estradiol	ki	0.0030	uM
Estrone	396108: Inhibition of 17beta-HSD1 assessed as conversion of [14C]estradiol to [14C]estrone using NADP+	ki	0.0030	uM
[5-(3-fluoro-4-hydroxyphenyl)thiophen-2-yl]-(2,4,5-trifluoro-3-hydroxyphenyl)methanone	1415114: Inhibition of human placental cytosolic 17beta-HSD1 using [3H]-E1 as substrate after 10 mins in presence of NADPH by radio-flow detector based analysis	ic50	0.0031	uM
N-[2,3-difluoro-5-[5-(2,4,5-trifluoro-3-hydroxybenzoyl)thiophen-2-yl]phenyl]-4-fluorobenzenesulfonamide	1564135: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis	ic50	0.0031	uM
[3-[[5-(4-hydroxy-3,5-dimethylphenyl)furan-2-carbonyl]-methylamino]-4-methylphenyl] sulfamate	1981867: Inhibition of human 17beta-HSD1 expressed in human T47D cells using [3H]E1 as substrate incubated for 1 hr followed by substrate addition measured after 40 mins in presence of E1 by HPLC analysis	ic50	0.0032	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases activity, increases expression, decreases expression	5
Valproic Acid	affects expression, affects reaction, decreases expression, increases methylation	5
bisphenol A	affects expression, increases expression, decreases reaction, decreases expression, increases reaction	4
Colforsin	affects reaction, affects expression, affects cotreatment, decreases expression, increases expression	3
Estradiol	increases expression, affects metabolic processing, increases chemical synthesis	2
Estrone	affects cotreatment, decreases reaction, increases reduction, affects metabolic processing, increases chemical synthesis	2
Flame Retardants	decreases expression, increases expression	2
NADP	affects cotreatment, decreases reaction, increases reduction, affects binding, increases activity	2
8-Bromo Cyclic Adenosine Monophosphate	decreases expression, increases reaction, increases expression	2
Halogenated Diphenyl Ethers	increases expression	2
aristolochic acid I	increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	increases expression	1
fluorene-9-bisphenol	decreases expression, decreases reaction, affects expression	1
cyhexatin	increases activity, increases expression	1
perflubron	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	decreases reaction, increases expression, affects reaction	1
triphenyltin hydroxide	increases activity, increases expression	1
2,4,5,2’,5’-pentachlorobiphenyl	decreases expression	1
tributyltin	increases activity, increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
HT-2 toxin	increases expression	1
trichostatin A	decreases expression	1
triphenyltin chloride	increases activity, increases expression	1
2,4-dibromophenol	increases expression	1
formestane	decreases activity	1
beta-lapachone	increases expression	1
cypermethrin	increases expression	1
dibutyldichlorotin	increases activity	1
tetrabromobisphenol A	decreases expression	1

ChEMBL screening assays

182 unique, capped per target: 180 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1013419	Binding	Inhibition of 17beta-HSD1 expressed in HEK 293 cells assessed as conversion of [14C]estrone to [14C]estradiol at 0.1 uM using NADH	Design and synthesis of bisubstrate inhibitors of type 1 17beta-hydroxysteroid dehydrogenase: overview and perspectives. — Eur J Med Chem
CHEMBL864128	Functional	Inhibition of 17-beta HSD1 in T47D cells at 10 uM	Modification of estrone at the 6, 16, and 17 positions: novel potent inhibitors of 17beta-hydroxysteroid dehydrogenase type 1. — J Med Chem

Clinical trials (associated diseases)

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