HPGD

Summary

HPGD (15-hydroxyprostaglandin dehydrogenase, HGNC:5154) is a protein-coding gene on chromosome 4q34.1, encoding 15-hydroxyprostaglandin dehydrogenase [NAD(+)] (P15428). Catalyzes the NAD-dependent dehydrogenation (oxidation) of a broad array of hydroxylated polyunsaturated fatty acids (mainly eicosanoids and docosanoids, including prostaglandins, lipoxins and resolvins), yielding their corresponding keto (oxo) metabolites.

This gene encodes a member of the short-chain nonmetalloenzyme alcohol dehydrogenase protein family. The encoded enzyme is responsible for the metabolism of prostaglandins, which function in a variety of physiologic and cellular processes such as inflammation. Mutations in this gene result in primary autosomal recessive hypertrophic osteoarthropathy and cranioosteoarthropathy. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3248 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypertrophic osteoarthropathy, primary, autosomal recessive, 1 (Definitive, GenCC) — +4 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 210 total — 24 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 79
• Druggable target: yes — 220 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000860

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5154
Approved symbol	HPGD
Name	15-hydroxyprostaglandin dehydrogenase
Location	4q34.1
Locus type	gene with protein product
Status	Approved
Aliases	SDR36C1
Ensembl gene	ENSG00000164120
Ensembl biotype	protein_coding
OMIM	601688
Entrez	3248

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000296521, ENST00000296522, ENST00000422112, ENST00000504433, ENST00000506910, ENST00000508330, ENST00000509512, ENST00000510835, ENST00000510901, ENST00000511499, ENST00000512410, ENST00000514584, ENST00000541923, ENST00000542498

RefSeq mRNA: 7 — MANE Select: NM_000860 NM_000860, NM_001145816, NM_001256301, NM_001256305, NM_001256306, NM_001256307, NM_001363574

CCDS: CCDS3821, CCDS54821, CCDS58933, CCDS58934, CCDS58935, CCDS87280

Canonical transcript exons

ENST00000296522 — 7 exons

Exon	Start	End
ENSE00002028043	174522359	174522488
ENSE00003491928	174508696	174508792
ENSE00003496323	174495548	174495624
ENSE00003522335	174521944	174522067
ENSE00003587014	174517971	174518077
ENSE00003660342	174493151	174493314
ENSE00003847689	174490175	174492094

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 99.23.

FANTOM5 (CAGE): breadth broad, TPM avg 51.7714 / max 13997.3525, expressed in 699 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54941	49.5120	643
203430	0.5397	101
54942	0.3627	123
203431	0.2425	80
203433	0.2042	62
54943	0.1879	76
203432	0.1635	69
54938	0.1446	61
54937	0.0874	40
203428	0.0829	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.23	gold quality
jejunal mucosa	UBERON:0000399	98.91	gold quality
lower esophagus mucosa	UBERON:0035834	98.81	gold quality
rectum	UBERON:0001052	97.32	gold quality
colonic mucosa	UBERON:0000317	96.91	gold quality
placenta	UBERON:0001987	96.77	gold quality
metanephric glomerulus	UBERON:0004736	96.58	gold quality
right lung	UBERON:0002167	96.52	gold quality
lower lobe of lung	UBERON:0008949	96.51	gold quality
renal glomerulus	UBERON:0000074	96.48	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.29	gold quality
mucosa of transverse colon	UBERON:0004991	96.00	gold quality
ileal mucosa	UBERON:0000331	95.97	gold quality
right lobe of liver	UBERON:0001114	95.85	gold quality
mucosa of urinary bladder	UBERON:0001259	95.68	gold quality
urinary bladder	UBERON:0001255	95.55	gold quality
transverse colon	UBERON:0001157	95.50	gold quality
duodenum	UBERON:0002114	95.37	gold quality
esophagus mucosa	UBERON:0002469	95.07	gold quality
upper arm skin	UBERON:0004263	94.99	gold quality
upper lobe of lung	UBERON:0008948	94.97	gold quality
upper lobe of left lung	UBERON:0008952	94.90	gold quality
upper leg skin	UBERON:0004262	94.88	gold quality
kidney epithelium	UBERON:0004819	94.87	gold quality
esophagus squamous epithelium	UBERON:0006920	94.85	gold quality
skin of leg	UBERON:0001511	94.75	gold quality
lung	UBERON:0002048	94.71	gold quality
epithelium of esophagus	UBERON:0001976	94.70	gold quality
vagina	UBERON:0000996	94.60	gold quality
large intestine	UBERON:0000059	94.45	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 26.

Experiment	Marker?	Max mean expression
E-MTAB-6505	yes	7663.01
E-MTAB-6678	yes	6855.04
E-MTAB-6308	yes	5266.58
E-HCAD-15	yes	4466.35
E-MTAB-6701	yes	3339.50
E-CURD-126	yes	3291.74
E-HCAD-23	yes	2556.81
E-MTAB-10553	yes	1930.12
E-MTAB-10662	yes	896.06
E-MTAB-9388	yes	322.26
E-HCAD-1	yes	47.16
E-CURD-88	yes	37.95
E-GEOD-135922	yes	25.00
E-HCAD-4	yes	22.60
E-HCAD-10	yes	19.48

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, ERG, ETS1, ETS2, ETV4, FOXA2, FOXO3, GLI2, HDAC2, NFIL3, PGR, SNAI1, SNAI2, SREBF1, TCF7L2, ZEB1

miRNA regulators (miRDB)

103 targeting HPGD, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• an examination of structure and function of this enzyme (PMID:12664592)
• in chorion trophoblast cells, endogenously produced corticotropin-releasing hormone exerts a tonic stimulatory effect on 15-hydroxyprostaglandin dehydrogenase activity (PMID:12679466)
• Cortisol inhibition and progesterone stimulation of PGDH may be mediated by progesterone receptor, but also via the glucocorticoid receptor, in chorion and placenta. (PMID:12788907)
• the genomic organisation of the complete human PGDH gene and characterise its transcriptional regulation (PMID:12914529)
• PGDH mRNA, protein, and enzyme activity are suppressed in the human ureter during obstruction. (PMID:14718596)
• At cesarean sections (unripe cervix), the level of 15-OH PGDH mRNA was significantly higher than the level in the ripe cervix at the time of partus, irrespective of the gestational length (PMID:15181076)
• 15-PGDH transcript and protein are both highly expressed by normal colonic epithelia but are nearly undetectable in colon cancers (PMID:15574495)
• Key NAD+-binding residues in HPGD were identified after site-directed mutagenesis studies. (PMID:15581601)
• The induction of 15-PGDH expression by dexamethasone and other glucocorticoids at the therapeutic level provides an additional biochemical mechanism for the anti-inflammatory action of these glucocorticoids. (PMID:15680906)
• COX-2 and 15-PGDH are regulated reciprocally in A549 cells (PMID:16632868)
• 15-Hydroxyprostaglandin dehydrogenase has a role in suppressing colon tumorigenesis (PMID:16880406)
• Data show that COX-1 inhibitors and sulindac sulfone, a non-COX inhibitor, increase 15-hydroxyprostaglandin-dehydrogenase (15-PGDH) activity, and suggest that 15-PGDH could be implicated in NSAIDs anti-proliferative effect. (PMID:16997128)
• in chorion trophoblast cells, CRHR1 and CRHR2 mediate divergent effects on PGDH expression, and this may provide a precise regulation of PGs levels from chorion to myometrium during pregnancy (PMID:17463062)
• 15-PGDH is downregulated by COX-2 in human gastric cancer and may contribute to the carcinogenesis and development of human gastric cancer (PMID:18174234)
• upon stimulation with the same upstream signals, different downstream intracellular pathways regulate PTGS2 and PGDH mRNA expression (PMID:18212353)
• 15-PGDH was expressed in human hair follicle mainly in melanocytes and keratinocytes (PMID:18328086)
• Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy (PMID:18500342)
• 15-PGDH is a direct downstream effector of HNF3beta and acts as a tumor suppressor in lung cancer. (PMID:18593902)
• Invasive apocrine carcinomas correspond to a distinct molecular subtype of breast carcinomas characterized by the expression of 15-prostaglandin dehydrogenase alone or in combination with a novel form of acyl-CoA synthetase medium-chain family member 1. (PMID:18632593)
• The involvement of 15-PGDH in the pathogenesis of Isolated congenital nail clubbing may open up interesting perspectives into the function of this enzyme in nail morphogenesis/development (PMID:18805827)
• class I histone deacetylase (HDACs), specifically HDAC2, and the transcriptional repressor Snail play a central role in the suppression of 15-hydroxyprostaglandin dehydrogenase expression. (PMID:19010907)
• Induced 15-PGDH expression may contribute to the inhibition of the invasive and metastatic capacity of colon cancer cells in vitro. (PMID:19034772)
• 15-PGDH is commonly down-regulated in NSCLC, an effect that contributes to the accumulation of multiple bioactive lipids in NSCLC. (PMID:19138967)
• Report homozygous mutations in the 15-hydroxyprostaglandin dehydrogenase gene in patients with primary hypertrophic osteoarthropathy. (PMID:19306095)
• demonstrates an important role of the 15-PGDH in regulation of local antitumor immune response and highlights the potential to be implemented to enhance the efficacy of cancer therapy and immunotherapy (PMID:19494278)
• The failure to identify any mutation in a family with an autosomal dominant type of isolated digital clubbing suggests that HPGD is not the major gene for this condition. (PMID:19568269)
• Results show that 15-PGDH is down-regulated in gastric cancer, which could potentially lead to accelerated tumor progression. (PMID:19584167)
• Bile acids inhibit NAD+-dependent 15-hydroxyprostaglandin dehydrogenase transcription in colonocytes. (PMID:19608733)
• positive correlation of COX-2 and VDR protein was found in the COV434 and HGL5 cells and an inverse correlation of 15-PGDH and VDR protein levels in all the investigated cell types (PMID:19667156)
• VDR protein levels were inversely correlated to the 15-PGDH protein levels and revealed that the MCF-10F cells had the highest VDR expression (PMID:19667157)
• These results suggest that enhanced PGE2 production proceeds through the expressions of COX-2 and microsomal PGES-1 and down-regulation of PGDH by SNAI2 in pancreatic tumors. (PMID:19820419)
• reduction of 15-PGDH is an independent predictor of poor survival associated with enhancement of cell proliferation in gastric adenocarcinoma. (PMID:19917058)
• Genetic variants in HPGD encoding 15-PGDH, appear to modulate colorectal risk. The present study appears to be the first to evaluate possible associations between genetic heterogeneity in HPGD and CRC risk. (PMID:20042636)
• Loss of PGDH expression contributes to a more malignant bladder cancer phenotype and may be necessary for bladder cancer development and/or progression. (PMID:20093479)
• The c.175_176delCT frameshift mutation appears to be recurrent and to be the commonest HPGD mutation in Caucasian families with primary hypertrophic osteoarthropathy. (PMID:20299379)
• analysis of expression of serum vitamin D receptor, cyclooxygenase-2, and 15-hydroxyprostaglandin dehydrogenase in benign and malignant ovarian tissue and 25-hydroxycholecalciferol and prostaglandin E2 in ovarian cancer patients (PMID:20304053)
• The study shows that cPLA2 and mPGES-1, in addition to COX-2, are constitutively overexpressed, and that 15-PGDH might be attenuated in colorectal cancer. Furthermore, cPLA2 and 15-PGDH as well as COX-2 could have an important role in tumor progression. (PMID:20635443)
• Reduced expression of 15-PGDH contributes to the elevated levels of PGs found in the skin following UVR exposure. (PMID:20643784)
• Results demonstrate that 15-PGDH acts as a tumor suppressor in gastric cancer and provide further validation for 15-PGDH as a potential therapeutic target for gastric cancer. (PMID:20699658)
• our data do not support the previously reported associations of HPGD tagSNPs and risk of colorectal cancer. (PMID:21047993)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	hpgd	ENSDARG00000012016
mus_musculus	Hpgd	ENSMUSG00000031613
rattus_norvegicus	Hpgd	ENSRNOG00000010610
drosophila_melanogaster	Adh	FBGN0000055
drosophila_melanogaster	Fbp2	FBGN0000640
drosophila_melanogaster	Pdh	FBGN0011693
drosophila_melanogaster	CG4842	FBGN0036620
drosophila_melanogaster	CG18814	FBGN0042137
caenorhabditis_elegans	Y92H12BL.5	WBGENE00022366

Protein

Protein identifiers

15-hydroxyprostaglandin dehydrogenase [NAD(+)] — P15428 (reviewed: P15428)

Alternative names: Eicosanoid/docosanoid dehydrogenase [NAD(+)], Prostaglandin dehydrogenase 1, Short chain dehydrogenase/reductase family 36C member 1

All UniProt accessions (6): P15428, D6RA66, D6RA83, D6RHF8, E9PBZ2, E9PD69

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the NAD-dependent dehydrogenation (oxidation) of a broad array of hydroxylated polyunsaturated fatty acids (mainly eicosanoids and docosanoids, including prostaglandins, lipoxins and resolvins), yielding their corresponding keto (oxo) metabolites. Decreases the levels of the pro-proliferative prostaglandins such as prostaglandin E2 (whose activity is increased in cancer because of an increase in the expression of cyclooxygenase 2) and generates oxo-fatty acid products that can profoundly influence cell function by abrogating pro-inflammatory cytokine expression. Converts resolvins E1, D1 and D2 to their oxo products, which represents a mode of resolvin inactivation. Resolvin E1 plays important roles during the resolution phase of acute inflammation, while resolvins D1 and D2 have a unique role in obesity-induced adipose inflammation.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in colon epithelium (at protein level).

Disease relevance. Hypertrophic osteoarthropathy, primary, autosomal recessive, 1 (PHOAR1) [MIM:259100] A disease characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. Other developmental anomalies include delayed closure of the cranial sutures and congenital heart disease. The disease is caused by variants affecting the gene represented in this entry. Cranioosteoarthropathy (COA) [MIM:259100] A form of osteoarthropathy characterized by swelling of the joints, digital clubbing, hyperhidrosis, delayed closure of the fontanels, periostosis, and variable patent ductus arteriosus. Pachydermia is not a prominent feature. The disease is caused by variants affecting the gene represented in this entry. Digital clubbing, isolated congenital (DIGC) [MIM:119900] A rare genodermatosis characterized by enlargement of the nail plate and terminal segments of the fingers and toes, resulting from proliferation of the connective tissues between the nail matrix and the distal phalanx. It is usually symmetrical and bilateral (in some cases unilateral). In nail clubbing usually the distal end of the nail matrix is relatively high compared to the proximal end, while the nail plate is complete but its dimensions and diameter more or less vary in comparison to normal. There may be different fingers and toes involved to varying degrees. Some fingers or toes are spared, but the thumbs are almost always involved. The disease is caused by variants affecting the gene represented in this entry.

Induction. Down-regulated by cortisol, dexamethasone and betamethasone. Down-regulated in colon cancer. Up-regulated by TGFB1.

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

Isoforms (5)

UniProt ID	Names	Canonical?
P15428-1	1	yes
P15428-2	2
P15428-3	3
P15428-4	4
P15428-5	5

RefSeq proteins (7): NP_000851, NP_001139288, NP_001243230, NP_001243234, NP_001243235, NP_001243236, NP_001350503 (=MANE)

Domains & families (InterPro)

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

Pfam: PF00106

Enzyme classification (BRENDA):

• EC 1.1.1.141 — 15-hydroxyprostaglandin dehydrogenase (NAD+) (BRENDA: 13 organisms, 86 substrates, 247 inhibitors, 94 Km, 25 kcat entries)
• EC 1.3.1.48 — 13,14-dehydro-15-oxoprostaglandin 13-reductase (BRENDA: 7 organisms, 86 substrates, 52 inhibitors, 65 Km, 28 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
NAD+	0.022–0.72	24
PROSTAGLANDIN E2	0.0016–0.059	17
(5Z,13E)-(15S)-11ALPHA,15-DIHYDROXY-9-OXOPROST-5	0.0012–0.026	16
PROSTAGLANDIN E1	0.0013–0.033	10
15-KETOPROSTAGLANDIN E1	0.001–0.0344	7
15-KETOPROSTAGLANDIN E2	0.0078–0.07	7
PROSTAGLANDIN F2ALPHA	0.0213–0.133	5
NADH	0.032–0.16	5
NADPH	0.008–0.0946	4
NADH	0.0156–0.0594	3
PROSTAGLANDIN A1	0.0045–0.038	3
15-KETOPROSTAGLANDIN F2ALPHA	0.0002–0.1088	3
(5Z,8E,10E,12S)-12-HYDROXY-5,8,10-HEPTADECATRIEN	0.0076–0.012	2
15-KETOPROSTAGLANDIN E2	0.0266–0.0528	2
PROSTAGLANDIN A2	0.003–0.022	2

Catalyzed reactions (Rhea), 12 shown:

• prostaglandin E2 + NAD(+) = 15-oxoprostaglandin E2 + NADH + H(+) (RHEA:11876)
• prostaglandin E1 + NAD(+) = 15-oxoprostaglandin E1 + NADH + H(+) (RHEA:16477)
• (15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + NAD(+) = 15-oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + NADH + H(+) (RHEA:23260)
• prostaglandin A1 + NAD(+) = 15-oxo-prostaglandin A1 + NADH + H(+) (RHEA:41263)
• lipoxin A4 + NAD(+) = 15-oxo-(5S,6R)-dihydroxy-(7E,9E,11Z,13E)-eicosatetraenoate + NADH + H(+) (RHEA:41572)
• 15-oxo-(5S,6R)-dihydroxy-(7E,9E,11Z)-eicosatrienoate + NADH + H(+) = (5S,6R,15S)-trihydroxy-(7E,9E,11Z)-eicosatrienoate + NAD(+) (RHEA:41596)
• (11R)-hydroxy-(5Z,8Z,12E,14Z)-eicosatetraenoate + NAD(+) = 11-oxo-(5Z,8Z,12E,14Z)-eicosatetraenoate + NADH + H(+) (RHEA:48640)
• 14-hydroxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate + NAD(+) = 14-oxo-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate + NADH + H(+) (RHEA:48952)
• resolvin E1 + NAD(+) = 18-oxo-resolvin E1 + NADH + H(+) (RHEA:49244)
• resolvin D1 + NAD(+) = 8-oxoresolvin D1 + NADH + H(+) (RHEA:50124)
• resolvin D1 + NAD(+) = 17-oxoresolvin D1 + NADH + H(+) (RHEA:50128)
• resolvin D2 + NAD(+) = 7-oxoresolvin D2 + NADH + H(+) (RHEA:53584)

UniProt features (54 total): helix 15, strand 10, binding site 8, splice variant 5, mutagenesis site 5, sequence variant 3, sequence conflict 3, turn 3, chain 1, active site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
2GDZ	X-RAY DIFFRACTION	1.65
9PFL	X-RAY DIFFRACTION	1.65
9PFM	X-RAY DIFFRACTION	1.88
8CVN	ELECTRON MICROSCOPY	2.4
8CWL	ELECTRON MICROSCOPY	2.9
8FD8	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15428-F1	96.82	0.95

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): 151 (proton acceptor)

Ligand- & substrate-binding residues (8): 12–20; 36–37; 63–65; 91; 138; 148; 151–155; 186–188

Mutagenesis-validated functional residues (5):

Position	Phenotype
148	loss of activity.
148	reduced affinity for nad and prostaglandin e2.
151	loss of activity.
151	loss 15-hydroxyprostaglandin dehydrogenase activity.
155	loss 15-hydroxyprostaglandin dehydrogenase activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2142700	Biosynthesis of Lipoxins (LX)
R-HSA-2162123	Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
R-HSA-9018676	Biosynthesis of D-series resolvins
R-HSA-9018896	Biosynthesis of E-series 18(S)-resolvins

MSigDB gene sets: 531 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, MODULE_93, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RESPONSE_TO_ETHANOL, GOBP_RESPONSE_TO_ESTRADIOL, chr4q34, GOBP_ARTERY_DEVELOPMENT, MEF2_02, GOBP_MUSCLE_CELL_PROLIFERATION, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_3, GOBP_POSITIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION

GO Biological Process (18): kidney development (GO:0001822), prostaglandin metabolic process (GO:0006693), transforming growth factor beta receptor signaling pathway (GO:0007179), female pregnancy (GO:0007565), parturition (GO:0007567), lipoxygenase pathway (GO:0019372), ovulation (GO:0030728), response to estradiol (GO:0032355), response to lipopolysaccharide (GO:0032496), positive regulation of apoptotic process (GO:0043065), response to ethanol (GO:0045471), negative regulation of cell cycle (GO:0045786), thrombin-activated receptor signaling pathway (GO:0070493), ductus arteriosus closure (GO:0097070), positive regulation of vascular associated smooth muscle cell proliferation (GO:1904707), regulation of prostaglandin catabolic process (GO:1905828), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (8): prostaglandin E receptor activity (GO:0004957), 15-hydroxyprostaglandin dehydrogenase (NAD+) activity (GO:0016404), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616), identical protein binding (GO:0042802), 15-hydroxyicosatetraenoate dehydrogenase activity (GO:0047034), NAD binding (GO:0051287), NAD+ binding (GO:0070403), oxidoreductase activity (GO:0016491)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), basolateral plasma membrane (GO:0016323), extracellular exosome (GO:0070062), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Biosynthesis of specialized proresolving mediators (SPMs)	1
Arachidonate metabolism	1
Biosynthesis of DHA-derived SPMs	1
Biosynthesis of EPA-derived SPMs	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
multi-organism reproductive process	2
multi-multicellular organism process	2
response to lipid	2
response to oxygen-containing compound	2
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	2
animal organ development	1
renal system development	1
prostanoid metabolic process	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
fatty acid metabolic process	1
icosanoid metabolic process	1
female gamete generation	1
multicellular organismal reproductive process	1
response to molecule of bacterial origin	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
response to alcohol	1
cell cycle	1
negative regulation of cellular process	1
regulation of cell cycle	1
G protein-coupled receptor signaling pathway	1
artery morphogenesis	1
positive regulation of smooth muscle cell proliferation	1
regulation of vascular associated smooth muscle cell proliferation	1
vascular associated smooth muscle cell proliferation	1
regulation of lipid catabolic process	1
prostaglandin catabolic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
prostaglandin receptor activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
protein binding	1
adenyl nucleotide binding	1
anion binding	1
NAD binding	1
catalytic activity	1

Protein interactions and networks

STRING

4054 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HPGD	HSD11B2	P80365	804
HPGD	SLCO2A1	Q92959	766
HPGD	PTGES	O14684	723
HPGD	HSD11B1	P28845	680
HPGD	PTGES3	Q15185	669
HPGD	PTGS2	P35354	667
HPGD	GAPDH	P00354	642
HPGD	PTGES2	Q9H7Z7	639
HPGD	PTGER4	P35408	625
HPGD	NR3C2	P08235	587
HPGD	PTGS1	P23219	570
HPGD	PTGR1	Q14914	565
HPGD	PPARG	P37231	541
HPGD	HSD17B2	P37059	522
HPGD	PTGER1	P34995	507

IntAct

6 interactions, top by confidence:

A	B	Type	Score
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
C18orf21	A2ML1	psi-mi:“MI:0914”(association)	0.350
SLC25A6	A2ML1	psi-mi:“MI:0914”(association)	0.350
MBNL1	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): HPGD (Affinity Capture-MS), HPGD (Proximity Label-MS), HPGD (Proximity Label-MS), HPGD (Affinity Capture-MS), HPGD (Affinity Capture-MS), HPGD (Affinity Capture-MS), HPGD (Affinity Capture-MS), HPGD (Affinity Capture-MS), HPGD (Affinity Capture-MS), HPGD (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A2VCW9, A4FUZ6, A8E657, A8XKG6, O02485, O08699, O17732, O48905, P11708, P13228, P14152, P15428, P46794, P51659, P51660, P57106, P70684, P93819, P97852, Q01373, Q08062, Q16698, Q29LW1, Q2TPA8, Q32PF2, Q3T0C2, Q3T145, Q4V8F9, Q54VM2, Q55FT1, Q59987, Q5RA68, Q66KC4, Q6DIY9, Q6P5L8, Q6PAB3, Q6PAY8, Q6YN16, Q7XDC8, Q7YRU4

Diamond homologs: A0A017SEY2, A0A023I4F1, A0A0C6DRT7, A0A1B7YCL6, A0A2P1DP77, A0A345BJN5, A0A482ND39, A0A4P8DJW5, A0A5B8YU33, A0AAW1NHX6, A2RVM0, B2X050, B6H062, B6HLP6, B8M9L2, C8V3Y7, D7UQ42, F4JJR8, G1XTZ5, G3Y422, G4MVZ5, G9N4A1, G9N4A6, I1S2J3, O48741, O75828, O80333, P00335, P0DXW2, P15428, P16232, P19992, P21218, P28845, P42317, P50199, P50203, P51975, P70684, P9WEF8

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SNAI2	“down-regulates quantity by repression”	HPGD	“transcriptional regulation”
HDAC2	“down-regulates quantity by repression”	HPGD	“transcriptional regulation”
SNAI1	“down-regulates quantity by repression”	HPGD	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	5
Uncertain significance	93
Likely benign	42
Benign	32

Top pathogenic / likely-pathogenic (29)

Variant ID	HGVS	Classification
1323063	NM_000860.6(HPGD):c.325-1G>C	Pathogenic
1459858	NC_000004.11:g.(?175429827)(175429963_?)del	Pathogenic
156026	NM_000860.6(HPGD):c.1A>T (p.Met1Leu)	Pathogenic
156027	NM_000860.6(HPGD):c.310_311del (p.Leu104fs)	Pathogenic
1708173	NM_000860.6(HPGD):c.498+1G>A	Pathogenic
1809761	NM_000860.6(HPGD):c.218-1G>A	Pathogenic
1906299	NM_000860.6(HPGD):c.218-1G>T	Pathogenic
2002334	NM_000860.6(HPGD):c.373del (p.Gln125fs)	Pathogenic
2116436	NM_000860.6(HPGD):c.361dup (p.Tyr121fs)	Pathogenic
2203595	NM_000860.6(HPGD):c.120del (p.Ala41fs)	Pathogenic
2499675	NM_000860.6(HPGD):c.662+2T>A	Pathogenic
2842323	NM_000860.6(HPGD):c.421+1G>A	Pathogenic
3362780	NM_000860.6(HPGD):c.324+5G>A	Pathogenic
3377527	NM_000860.6(HPGD):c.189C>A (p.Cys63Ter)	Pathogenic
3631858	NM_000860.6(HPGD):c.325-2A>C	Pathogenic
3691622	NM_000860.6(HPGD):c.202C>T (p.Gln68Ter)	Pathogenic
3692279	NM_000860.6(HPGD):c.520_523dup (p.Gly175fs)	Pathogenic
3718029	NM_000860.6(HPGD):c.421+1G>T	Pathogenic
4775513	NM_000860.6(HPGD):c.2T>C (p.Met1Thr)	Pathogenic
7917	NM_000860.6(HPGD):c.418G>C (p.Ala140Pro)	Pathogenic
7918	NM_000860.6(HPGD):c.232_241delinsCA (p.Val78fs)	Pathogenic
7919	NM_000860.6(HPGD):c.175_176del (p.Leu59fs)	Pathogenic
973741	NM_000860.6(HPGD):c.34G>A (p.Gly12Ser)	Pathogenic
973742	NM_000860.6(HPGD):c.313C>T (p.Gln105Ter)	Pathogenic
2423428	NC_000004.11:g.(?175429827)(175439248_?)del	Likely pathogenic
2440745	NM_000860.6(HPGD):c.307del (p.Thr103fs)	Likely pathogenic
3891348	NM_000860.6(HPGD):c.453T>G (p.Tyr151Ter)	Likely pathogenic
599096	NM_000860.6(HPGD):c.446C>G (p.Pro149Arg)	Likely pathogenic
7920	NM_000860.6(HPGD):c.577T>C (p.Ser193Pro)	Likely pathogenic

SpliceAI

1138 predictions. Top by Δscore:

Variant	Effect	Δscore
4:174492090:GTGGG:G	acceptor_gain	1.0000
4:174492091:TGGG:T	acceptor_gain	1.0000
4:174492092:GGG:G	acceptor_gain	1.0000
4:174492093:GG:G	acceptor_gain	1.0000
4:174492093:GGC:G	acceptor_loss	1.0000
4:174492094:GCTAA:G	acceptor_loss	1.0000
4:174492095:C:CC	acceptor_gain	1.0000
4:174492095:CT:C	acceptor_loss	1.0000
4:174495547:CCG:C	donor_gain	1.0000
4:174521943:CCT:C	donor_gain	1.0000
4:174493149:A:AC	donor_gain	0.9900
4:174493149:ACT:A	donor_gain	0.9900
4:174493150:C:CT	donor_gain	0.9900
4:174493150:CTC:C	donor_gain	0.9900
4:174493315:C:CC	acceptor_gain	0.9900
4:174493349:C:CT	acceptor_gain	0.9900
4:174493350:A:C	acceptor_gain	0.9900
4:174493356:A:C	acceptor_gain	0.9900
4:174508799:C:CT	acceptor_gain	0.9900
4:174508806:A:C	acceptor_gain	0.9900
4:174521938:TCTTA:T	donor_loss	0.9900
4:174521939:CTTA:C	donor_loss	0.9900
4:174521940:TTACC:T	donor_loss	0.9900
4:174521941:TACCT:T	donor_loss	0.9900
4:174521942:ACC:A	donor_loss	0.9900
4:174521943:C:G	donor_loss	0.9900
4:174522064:CTAC:C	acceptor_gain	0.9900
4:174522068:C:CA	acceptor_loss	0.9900
4:174522353:GCTTA:G	donor_loss	0.9900
4:174522354:CTTAC:C	donor_loss	0.9900

AlphaMissense

1753 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:174493267:A:C	C182W	0.997
4:174495588:G:T	A153D	0.997
4:174495558:C:G	R163P	0.996
4:174495581:C:A	K155N	0.996
4:174495581:C:G	K155N	0.996
4:174508712:A:C	N135K	0.996
4:174508712:A:T	N135K	0.996
4:174518025:A:C	N90K	0.996
4:174518025:A:T	N90K	0.996
4:174495576:C:T	G157D	0.995
4:174495595:A:G	Y151H	0.995
4:174493269:A:G	C182R	0.994
4:174495564:A:G	F161S	0.994
4:174517974:A:C	N107K	0.994
4:174517974:A:T	N107K	0.994
4:174522399:C:T	G18D	0.994
4:174495624:C:T	G141E	0.993
4:174508696:C:G	G141R	0.993
4:174508696:C:T	G141R	0.993
4:174508765:C:G	G118R	0.993
4:174522406:C:G	G16R	0.993
4:174493268:C:T	C182Y	0.992
4:174495556:A:G	S164P	0.992
4:174495582:T:G	K155T	0.992
4:174508705:A:G	S138P	0.992
4:174508764:C:T	G118D	0.992
4:174493250:G:A	T188I	0.991
4:174493256:A:T	V186D	0.991
4:174495590:A:C	C152W	0.991
4:174522417:C:T	G12D	0.991

dbSNP variants (sampled 300 via entrez): RS1000056805 (4:174513494 C>A,T), RS1000072415 (4:174492787 A>G), RS1000298946 (4:174523745 G>A), RS1000301332 (4:174516598 T>C), RS1000511651 (4:174510200 T>A,C), RS1000640575 (4:174519361 C>T), RS1000674886 (4:174519162 A>G), RS1000948086 (4:174512222 T>C), RS1001056676 (4:174497386 A>G), RS1001124417 (4:174509492 G>A), RS1001141738 (4:174506054 T>C), RS1001160163 (4:174520445 T>C), RS1001305547 (4:174522556 T>C), RS1001322681 (4:174502544 G>A), RS1001409738 (4:174515768 A>G,T)

Disease associations

OMIM: gene MIM:601688 | disease phenotypes: MIM:259100, MIM:119900

GenCC curated gene-disease

Disease	Classification	Inheritance
hypertrophic osteoarthropathy, primary, autosomal recessive, 1	Definitive	Autosomal recessive
primary hypertrophic osteoarthropathy	Strong	Autosomal recessive
isolated congenital digital clubbing	Supportive	Autosomal dominant
cranio-osteoarthropathy	Supportive	Autosomal recessive
pachydermoperiostosis	Supportive	Autosomal recessive

Mondo (5): hypertrophic osteoarthropathy, primary, autosomal recessive, 1 (MONDO:0024546), isolated congenital digital clubbing (MONDO:0007343), cranio-osteoarthropathy (MONDO:0015466), (MONDO:0009799), primary hypertrophic osteoarthropathy (MONDO:0016620)

Orphanet (3): Cranio-osteoarthropathy (Orphanet:1525), Pachydermoperiostosis (Orphanet:2796), Isolated nail clubbing (Orphanet:217059)

HPO phenotypes

79 total (30 of 79 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000239	Large fontanelles
HP:0000280	Coarse facial features
HP:0000508	Ptosis
HP:0000767	Pectus excavatum
HP:0000771	Gynecomastia
HP:0000845	Elevated circulating growth hormone concentration
HP:0000890	Long clavicles
HP:0000929	Abnormal skull morphology
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000951	Abnormality of the skin
HP:0000964	Eczematoid dermatitis
HP:0000969	Edema
HP:0000972	Palmoplantar hyperkeratosis
HP:0000975	Hyperhidrosis
HP:0000982	Palmoplantar keratoderma
HP:0001051	Seborrheic dermatitis
HP:0001061	Acne
HP:0001070	Mottled pigmentation
HP:0001072	Thickened skin
HP:0001217	Clubbing
HP:0001231	Abnormal fingernail morphology
HP:0001369	Arthritis
HP:0001376	Limitation of joint mobility
HP:0001386	Joint swelling
HP:0001387	Joint stiffness
HP:0001500	Broad finger
HP:0001519	Disproportionate tall stature

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003121_1	Alcohol dependence	8.000000e-07
GCST004068_46	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	3.000000e-06
GCST009391_1149	Metabolite levels	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010457	Alpha ketoglutarate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010004	Osteoarthropathy, Primary Hypertrophic	C05.116.725; C05.550.648; C16.320.718

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293255 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

220 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 710,803 (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
CHEMBL101	PHENYLBUTAZONE	4	59,455
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1042	CHOLECALCIFEROL	4	64,162
CHEMBL1057	FLUORESCEIN	4	329,940
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL1072	BUMETANIDE	4	22,087
CHEMBL1082607	SALMETEROL XINAFOATE	4	15,201
CHEMBL1086	DIBUCAINE	4	17,231
CHEMBL1091250	INDIGOTINDISULFONATE	4	340
CHEMBL11359	CISPLATIN	4
CHEMBL117785	TETRABENAZINE	4	9,645
CHEMBL119	TRIMETREXATE	4	57,002
CHEMBL1200323	LABETALOL HYDROCHLORIDE	4	2,621
CHEMBL1200471	PYRITHIONE ZINC	4	24,834
CHEMBL1200561	DOXAZOSIN MESYLATE	4	11,917
CHEMBL1200586	PRILOCAINE HYDROCHLORIDE	4	907
CHEMBL1200613	TOLMETIN SODIUM	4	35
CHEMBL1200761	CHLOROTRIANISENE	4	23,246
CHEMBL1200798	TRAZODONE HYDROCHLORIDE	4	8,178
CHEMBL1200896	DINOPROST TROMETHAMINE	4	1,764
CHEMBL1200938	METHYSERGIDE MALEATE	4
CHEMBL1200970	ETHOPROPAZINE HYDROCHLORIDE	4
CHEMBL1201038	ACRISORCIN	4
CHEMBL1201082	FLUOXETINE HYDROCHLORIDE	4
CHEMBL1201119	LIOTHYRONINE SODIUM	4
CHEMBL1201236	CARBIDOPA ANHYDROUS	4
CHEMBL1206	ETHOPROPAZINE	4
CHEMBL1208422	ROSE BENGAL FREE ACID	4
CHEMBL121	ROSIGLITAZONE	4
CHEMBL1219	RABEPRAZOLE	4

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7349744	HPGD		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Prostaglandin synthases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 3 [PMID: 21650226]	Inhibition	8.1	pIC50
ML148	Inhibition	7.25	pIC50

Binding affinities (BindingDB)

380 measured of 563 human assays (563 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-butylsulfinyl-4-phenyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine	IC50	0.76 nM	US-9790233: Compositions and methods of modulating 15-PGDH activity
2-butylsulfinyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine	IC50	0.97 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
2-butylsulfinyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	IC50	0.97 nM	US-9790233: Compositions and methods of modulating 15-PGDH activity
6-butylsulfinyl-4-phenyl-2-(1,3-thiazol-2-yl)thieno[2,3-d]pyrimidin-5-amine	IC50	1.14 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
2-butylsulfinyl-4-(2,3-dimethylimidazol-4-yl)-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	IC50	1.3 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
2-[(R)-butylsulfinyl]-4-phenyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine	IC50	1.34 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
2-butylsulfinyl-4-phenyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	IC50	1.37 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
2-butylsulfinyl-6-(1,3-oxazol-2-yl)-4-phenylthieno[2,3-b]pyridin-3-amine	IC50	1.37 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
1-[3-amino-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-2-yl]pentan-1-one	IC50	1.41 nM	US-9790233: Compositions and methods of modulating 15-PGDH activity
2-butylsulfinyl-4-methyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine	IC50	1.43 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
[7-amino-3-(1,3-benzoxazol-6-yl)thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
(7-amino-3-thiophen-2-ylthieno[2,3-b]pyrazin-6-yl)-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
(7-amino-3-pyrimidin-5-ylthieno[2,3-b]pyrazin-6-yl)-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
[7-amino-3-(1,3-thiazol-5-yl)thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
[7-amino-3-(2,3-dihydro-1,4-benzodioxin-6-yl)thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
[7-amino-3-(3,5-dimethyl-1,2-oxazol-4-yl)thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
(7-amino-3-quinoxalin-6-ylthieno[2,3-b]pyrazin-6-yl)-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
[7-amino-3-(6-amino-3-pyridinyl)thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
(7-amino-3-imidazo[1,2-a]pyridin-6-ylthieno[2,3-b]pyrazin-6-yl)-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
5-[7-amino-6-(piperidine-1-carbonyl)thieno[2,3-b]pyrazin-3-yl]-1-methylpyridin-2-one	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
[7-amino-3-(6-methoxy-3-pyridinyl)thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
(7-amino-3-quinolin-6-ylthieno[2,3-b]pyrazin-6-yl)-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
(7-amino-3-isoquinolin-4-ylthieno[2,3-b]pyrazin-6-yl)-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
(7-amino-3-pyridin-4-ylthieno[2,3-b]pyrazin-6-yl)-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
[7-amino-3-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
[7-amino-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
[7-amino-3-(2-methyl-4-pyridinyl)thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
(7-amino-3-quinolin-3-ylthieno[2,3-b]pyrazin-6-yl)-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
[7-amino-3-(2,6-dichlorophenyl)thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
(7-amino-3-naphthalen-2-ylthieno[2,3-b]pyrazin-6-yl)-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
[7-amino-3-(6-methyl-3-pyridinyl)thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
(7-amino-3-quinolin-7-ylthieno[2,3-b]pyrazin-6-yl)-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
[7-amino-3-(3H-benzimidazol-5-yl)thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
4-[7-amino-6-(piperidine-1-carbonyl)thieno[2,3-b]pyrazin-3-yl]-1-methylpyridin-2-one	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
[7-amino-3-(5-methoxy-3-pyridinyl)thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
[7-amino-3-(6-fluoro-3-pyridinyl)thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
[7-amino-3-(2-amino-4-pyridinyl)thieno[2,3-b]pyrazin-6-yl]-piperidin-1-ylmethanone	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
5-[7-amino-6-(piperidine-1-carbonyl)thieno[2,3-b]pyrazin-3-yl]-2-methyl-3H-isoindol-1-one	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
6-[7-amino-6-(piperidine-1-carbonyl)thieno[2,3-b]pyrazin-3-yl]-2-methylisoquinolin-1-one	IC50	1.75 nM	US-20250154162: COMPOUND FOR REGULATING AND CONTROLLING 15-PGDH ACTIVITY AND PREPARATION METHOD THEREFOR
2-butylsulfinyl-4,6-bis(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	IC50	1.83 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
ethyl 3-amino-2-propylsulfinyl-6-thiophen-2-ylthieno[2,3-b]pyridine-4-carboxylate	IC50	1.99 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
4-phenyl-2-propylsulfinyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine	IC50	2.05 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
2-(3-methoxypropylsulfinyl)-4-phenyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine	IC50	2.09 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
2-butylsulfinyl-4-(1-methylimidazol-2-yl)-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	IC50	2.13 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
2-butylsulfinyl-4-(2-methyl-1H-imidazol-5-yl)-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	IC50	2.3 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
6-butylsulfinyl-4-phenyl-2-thiophen-2-ylthieno[2,3-d]pyrimidin-5-amine	IC50	2.4 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
6-butylsulfanyl-4-phenyl-2-thiophen-2-ylthieno[2,3-d]pyrimidin-5-amine	IC50	2.4 nM	US-10301320: Compositions and methods of modulating 15-PGDH activity
3-[3-amino-2-butylsulfinyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-4-yl]-N-prop-2-enylbenzamide	IC50	2.5 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
[4-[3-amino-2-butylsulfinyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-4-yl]phenyl]methanol	IC50	2.5 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity
[4-[3-amino-2-butylsulfinyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-4-yl]phenyl]methyl acetate	IC50	2.5 nM	US-9789116: Compositions and methods of modulating short-chain dehydrogenase activity

ChEMBL bioactivities

3719 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	IC50	0.05	nM	CHEMBL6170291
10.30	IC50	0.05	nM	CHEMBL6151495
10.22	Ki	0.06	nM	CHEMBL4070789
10.22	IC50	0.06	nM	CHEMBL6173663
10.22	IC50	0.06	nM	CHEMBL6152103
10.00	Ki	0.1	nM	CHEMBL4061483
9.66	IC50	0.22	nM	CHEMBL6170291
9.57	IC50	0.27	nM	CHEMBL6173663
9.55	IC50	0.28	nM	CHEMBL6152103
9.52	IC50	0.3	nM	CHEMBL6151495
9.30	IC50	0.5	nM	CHEMBL5915247
9.22	IC50	0.6	nM	CHEMBL5856725
9.12	IC50	0.76	nM	CHEMBL4061483
9.01	IC50	0.97	nM	CHEMBL4072253
9.01	IC50	0.97	nM	CHEMBL5902819
9.00	IC50	1	nM	CHEMBL4072253
9.00	IC50	1	nM	CHEMBL4060121
8.94	IC50	1.14	nM	CHEMBL4060121
8.91	IC50	1.23	nM	CHEMBL4061483
8.89	IC50	1.3	nM	CHEMBL4070789
8.89	IC50	1.3	nM	CHEMBL5794676
8.87	IC50	1.34	nM	CHEMBL4091103
8.86	IC50	1.37	nM	CHEMBL4070824
8.86	IC50	1.37	nM	CHEMBL4097930
8.85	IC50	1.4	nM	CHEMBL4070824
8.85	IC50	1.4	nM	CHEMBL4097930
8.85	IC50	1.41	nM	CHEMBL5902819
8.85	IC50	1.43	nM	CHEMBL5763449
8.85	IC50	1.41	nM	CHEMBL5892978
8.82	IC50	1.5	nM	CHEMBL4091103
8.82	IC50	1.5	nM	CHEMBL5906331
8.80	IC50	1.6	nM	CHEMBL5220078
8.77	IC50	1.7	nM	CHEMBL5219440
8.77	IC50	1.7	nM	CHEMBL5220207
8.74	IC50	1.8	nM	CHEMBL4071206
8.74	IC50	1.8	nM	CHEMBL4092806
8.74	IC50	1.8	nM	CHEMBL4065035
8.74	IC50	1.83	nM	CHEMBL4071206
8.74	IC50	1.8	nM	CHEMBL5856919
8.74	Potency	1.8	nM	CHEMBL1361022
8.72	IC50	1.9	nM	CHEMBL4060870
8.70	IC50	2	nM	CHEMBL4076946
8.70	IC50	2	nM	CHEMBL4076321
8.70	IC50	2	nM	CHEMBL5218684
8.70	IC50	1.99	nM	CHEMBL4076946
8.69	IC50	2.05	nM	CHEMBL4087830
8.68	IC50	2.1	nM	CHEMBL4087830
8.68	IC50	2.1	nM	CHEMBL4090222
8.68	IC50	2.1	nM	CHEMBL4082770
8.68	IC50	2.09	nM	CHEMBL4090222

PubChem BioAssay actives

240 with measured affinity, of 414 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(R)-butylsulfinyl]-4-(2,3-dimethylimidazol-4-yl)-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ki	0.0001	uM
2-butylsulfinyl-4-phenyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine	1482410: Inhibition of 15-PGDH (unknown origin) using PGE2 as substrate preincubated for 12 hrs followed by dialysis for 12 hrs and subsequent addition of NAD+ measured after 12 hrs	ki	0.0001	uM
6-butylsulfinyl-4-phenyl-2-(1,3-thiazol-2-yl)thieno[2,3-d]pyrimidin-5-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0010	uM
2-butylsulfinyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0010	uM
2-butylsulfinyl-6-(1,3-oxazol-2-yl)-4-phenylthieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0014	uM
2-butylsulfinyl-4-phenyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0014	uM
2-[(R)-butylsulfinyl]-4-phenyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0015	uM
[3-(2-aminopyrimidin-5-yl)quinoxalin-6-yl]-piperidin-1-ylmethanone	1918507: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins	ic50	0.0016	uM
(3-isoquinolin-6-ylquinoxalin-6-yl)-piperidin-1-ylmethanone	1918507: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins	ic50	0.0017	uM
5-[7-(piperidine-1-carbonyl)quinoxalin-2-yl]pyridine-2-carboxylic acid	1918507: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins	ic50	0.0017	uM
2-butylsulfinyl-4-(1-methylimidazol-2-yl)-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0018	uM
2-butylsulfinyl-4,6-bis(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0018	uM
4-(2,3-dimethylimidazol-4-yl)-2-(2-methoxyethylsulfinyl)-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0018	uM
2-[4-[3-amino-2-butylsulfinyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-4-yl]phenoxy]ethanol	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0019	uM
2-butylsulfinyl-4-(2-cyclopropyl-3-methylimidazol-4-yl)-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0020	uM
ethyl 3-amino-2-propylsulfinyl-6-thiophen-2-ylthieno[2,3-b]pyridine-4-carboxylate	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0020	uM
6-[7-(piperidine-1-carbonyl)quinoxalin-2-yl]-2H-isoquinolin-1-one	1918507: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins	ic50	0.0020	uM
2-(3-methoxypropylsulfinyl)-4-phenyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0021	uM
4-phenyl-2-propylsulfinyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0021	uM
1-[[4-[3-amino-2-butylsulfinyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-4-yl]phenyl]methyl]-3-ethylurea	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0021	uM
2-butylsulfinyl-4-(2-methyl-1H-imidazol-5-yl)-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0023	uM
piperidin-1-yl-(3-quinolin-6-ylquinoxalin-6-yl)methanone	1918507: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins	ic50	0.0023	uM
6-[7-(piperidine-1-carbonyl)quinoxalin-2-yl]-1H-quinolin-2-one	1918507: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins	ic50	0.0023	uM
6-butylsulfinyl-4-phenyl-2-thiophen-2-ylthieno[2,3-d]pyrimidin-5-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0024	uM
[4-[3-amino-2-butylsulfinyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-4-yl]phenyl]methanol	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0025	uM
N-[[4-[3-amino-2-butylsulfinyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-4-yl]phenyl]methyl]acetamide	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0025	uM
6-butylsulfinyl-2-(1,3-oxazol-4-yl)-4-phenylthieno[2,3-d]pyrimidin-5-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0026	uM
2-butylsulfinyl-4-pyridin-3-yl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0026	uM
2-pentylsulfinyl-4-phenyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0026	uM
2-butylsulfinyl-4-(2,3-dimethylimidazol-4-yl)-6-(4-methyl-1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0028	uM
[3-[6-(methylamino)-3-pyridinyl]quinoxalin-6-yl]-piperidin-1-ylmethanone	1918507: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins	ic50	0.0028	uM
2-[4-[3-amino-2-butylsulfinyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-4-yl]phenyl]ethanol	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0029	uM
2-methyl-6-[7-(piperidine-1-carbonyl)quinoxalin-2-yl]isoquinolin-1-one	1918507: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins	ic50	0.0030	uM
[3-(6-amino-3-pyridinyl)quinoxalin-6-yl]-piperidin-1-ylmethanone	1918507: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins	ic50	0.0030	uM
4-phenyl-2-propan-2-ylsulfinyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0032	uM
2-butylsulfinyl-4-(2-chloro-3-methylimidazol-4-yl)-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0032	uM
4-(2,3-dimethylimidazol-4-yl)-2-(3-methoxypropylsulfinyl)-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0033	uM
3-[3-amino-2-butylsulfinyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-4-yl]-N-(2-hydroxyethyl)benzamide	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0034	uM
4-[3-amino-2-butylsulfinyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-4-yl]benzoic acid	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0034	uM
[4-[3-amino-2-butylsulfinyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-4-yl]phenyl]methyl N-ethylcarbamate	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0034	uM
[4-[3-amino-2-butylsulfinyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-4-yl]phenyl]methyl 2-(dimethylamino)acetate	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0035	uM
[3-(6-methoxy-3-pyridinyl)quinoxalin-6-yl]-piperidin-1-ylmethanone	1918507: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins	ic50	0.0035	uM
2-[4-[3-amino-2-butylsulfinyl-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-4-yl]phenyl]propan-2-ol	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0036	uM
6-butylsulfinyl-2-(1-methylimidazol-2-yl)-4-phenylthieno[2,3-d]pyrimidin-5-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0037	uM
2-(3-chloropropylsulfinyl)-4-phenyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine	1482373: Inhibition of recombinant human C-terminal 6xHis-tagged 15-PGDH expressed in Escherichia coli using PGE2 as substrate after 15 mins in presence of NAD(+) by fluorescence assay	ic50	0.0040	uM
(5Z)-5-[[3-bromo-4-(2-phenylethoxy)phenyl]methylidene]-1,3-thiazolidine-2,4-dione	1194317: Inhibition of 15-PGDH (unknown origin) by fluorescence spectrophotometry	ic50	0.0040	uM
piperidin-1-yl-(3-pyrimidin-5-ylquinoxalin-6-yl)methanone	1918507: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins	ic50	0.0040	uM
piperidin-1-yl-(3-pyridin-4-ylquinoxalin-6-yl)methanone	1918507: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins	ic50	0.0040	uM
[3-(1-methoxyisoquinolin-6-yl)quinoxalin-6-yl]-piperidin-1-ylmethanone	1918507: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins	ic50	0.0040	uM
morpholin-4-yl-[4-[7-(piperidine-1-carbonyl)quinoxalin-2-yl]phenyl]methanone	1918507: Inhibition of 15-PGDH (unknown origin) using NAD as substrate measured for 3.5 mins	ic50	0.0040	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
Estradiol	affects cotreatment, decreases expression, increases expression, decreases reaction	5
Indomethacin	affects binding, affects cotreatment, increases expression, increases reaction, increases activity	5
Benzo(a)pyrene	decreases expression, increases methylation	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
Tretinoin	affects expression, increases expression	3
Dinoprostone	affects binding, affects cotreatment, affects abundance, increases metabolic processing	3
Aflatoxin B1	decreases methylation, affects expression, decreases expression	3
sodium arsenite	decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
perfluorooctane sulfonic acid	decreases expression	2
entinostat	increases expression, affects cotreatment	2
Arsenic Trioxide	decreases expression, increases expression	2
Diclofenac	affects binding, affects cotreatment, increases activity, increases expression	2
Diethylhexyl Phthalate	affects cotreatment, decreases expression, decreases reaction, increases expression	2
Ibuprofen	affects expression, increases activity, increases expression	2
Methotrexate	increases expression	2
Tetradecanoylphorbol Acetate	increases expression, increases reaction, decreases reaction, increases activity	2
Mifepristone	increases expression, decreases expression, decreases reaction, increases activity	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
geldanamycin	decreases reaction, increases activity, increases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
diethyl phthalate	affects cotreatment, decreases expression, decreases reaction	1
sodium arsenate	decreases expression, increases abundance	1
testosterone undecanoate	increases expression	1
decabromobiphenyl ether	increases expression	1

ChEMBL screening assays

38 unique, capped per target: 33 binding, 3 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1069650	Binding	Inhibition of human 15PGDH expressed in Escherichia coli BL-21 by fluorescence spectrophotometry	Synthesis and SAR of thiazolidinedione derivatives as 15-PGDH inhibitors. — Bioorg Med Chem
CHEMBL1614038	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of HPGD (15-Hydroxyprostaglandin Dehydrogenase). (Class of assay: confirmatory) [Related pubchem assays: 2429 (Confirmation qHTS Assay for Inhibitors of HPGD (15-Hydroxyprostaglandin Dehydrogenase	PubChem BioAssay data set
CHEMBL3254514	ADMET	Stability of the compound assessed as prostaglandin 15-hydroxydehydrogenase (unknown origin)-mediated metabolite formation	11,12-Secoprostaglandins. 1. Acylhydroxyalkanoic acids and related compounds. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4XP	SDQLCHi032-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02438709	PHASE3	UNKNOWN	Effect Observation Study of COX-2 Inhibitor to Treat Primary Hypertrophic Osteoarthropathy