HPGDS

Summary

HPGDS (hematopoietic prostaglandin D synthase, HGNC:17890) is a protein-coding gene on chromosome 4q22.3, encoding Hematopoietic prostaglandin D synthase (O60760). Bifunctional enzyme which catalyzes both the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation, and the conjugation of glutathione with a wide range of aryl halides and organic isothiocyana….

Prostaglandin-D synthase is a sigma class glutathione-S-transferase family member. The enzyme catalyzes the conversion of PGH2 to PGD2 and plays a role in the production of prostanoids in the immune system and mast cells. The presence of this enzyme can be used to identify the differentiation stage of human megakaryocytes.

Source: NCBI Gene 27306 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 31 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014485

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17890
Approved symbol	HPGDS
Name	hematopoietic prostaglandin D synthase
Location	4q22.3
Locus type	gene with protein product
Status	Approved
Aliases	GSTS, PGDS, H-PGDS, PGD2, GSTS1-1, GSTS1
Ensembl gene	ENSG00000163106
Ensembl biotype	protein_coding
OMIM	602598
Entrez	27306

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000295256, ENST00000506331, ENST00000514774, ENST00000944232

RefSeq mRNA: 1 — MANE Select: NM_014485 NM_014485

CCDS: CCDS3640

Canonical transcript exons

ENST00000295256 — 6 exons

Exon	Start	End
ENSE00001071668	94302146	94302244
ENSE00001302624	94298535	94299644
ENSE00003491682	94334497	94334638
ENSE00003547326	94317873	94317965
ENSE00003595243	94308634	94308743
ENSE00003889109	94342795	94342836

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 94.35.

FANTOM5 (CAGE): breadth broad, TPM avg 16.6473 / max 6957.6611, expressed in 343 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53185	13.5588	299
53186	2.9145	276
53184	0.1740	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.35	gold quality
placenta	UBERON:0001987	85.83	gold quality
calcaneal tendon	UBERON:0003701	85.48	gold quality
gall bladder	UBERON:0002110	85.12	gold quality
layer of synovial tissue	UBERON:0007616	83.34	gold quality
amniotic fluid	UBERON:0000173	82.46	gold quality
mucosa of transverse colon	UBERON:0004991	82.31	gold quality
tendon	UBERON:0000043	81.02	gold quality
rectum	UBERON:0001052	80.13	gold quality
synovial joint	UBERON:0002217	78.61	gold quality
tendon of biceps brachii	UBERON:0008188	76.91	gold quality
skin of hip	UBERON:0001554	76.35	gold quality
upper lobe of left lung	UBERON:0008952	75.37	gold quality
upper lobe of lung	UBERON:0008948	74.59	gold quality
cranial nerve II	UBERON:0000941	74.46	gold quality
right coronary artery	UBERON:0001625	74.34	gold quality
smooth muscle tissue	UBERON:0001135	74.21	gold quality
lung	UBERON:0002048	74.20	gold quality
visceral pleura	UBERON:0002401	74.14	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.82	gold quality
small intestine Peyer’s patch	UBERON:0003454	73.37	gold quality
right lung	UBERON:0002167	73.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	72.99	gold quality
pleura	UBERON:0000977	72.95	gold quality
omental fat pad	UBERON:0010414	72.78	gold quality
peritoneum	UBERON:0002358	72.69	gold quality
subcutaneous adipose tissue	UBERON:0002190	72.67	gold quality
jejunal mucosa	UBERON:0000399	72.50	gold quality
lower esophagus muscularis layer	UBERON:0035833	72.45	gold quality
adipose tissue of abdominal region	UBERON:0007808	72.40	gold quality

Single-cell (SCXA)

Detected in 33 experiment(s), a significant marker in 33.

Experiment	Marker?	Max mean expression
E-MTAB-8221	yes	3716.65
E-MTAB-6505	yes	3098.05
E-MTAB-10042	yes	3042.16
E-MTAB-9906	yes	2434.47
E-MTAB-6308	yes	2196.00
E-GEOD-130148	yes	2164.31
E-MTAB-8410	yes	2152.02
E-MTAB-7407	yes	2105.47
E-MTAB-8322	yes	1898.64
E-HCAD-10	yes	1853.40
E-MTAB-8142	yes	1793.17
E-MTAB-9067	yes	1704.89
E-MTAB-10553	yes	1615.36
E-HCAD-36	yes	1556.04
E-CURD-79	yes	1479.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, ESR1, FOS, JUN, JUNB, JUND, MAFK, MBD2, MITF, NFE2L2, NKRF, NR1H4, PITX2, POU2F1, RARB, SOX9, SP1, SP3, SRY, TBX1, TFAP2A, TP53

miRNA regulators (miRDB)

48 targeting HPGDS, 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-548C-3P	99.99	74.01	7587
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487

Literature-anchored findings (GeneRIF, showing 14)

• New polymorphisms of haematopoietic prostaglandin D synthase (PMID:12002745)
• crystal structure when bound to glutathione and Ca+ or Mg+, and enzyme activation (PMID:12627223)
• Data suggest that the suppressive effect of hematopoietic prostaglandin D synthase on lung injury could be partly mediated by edema formation and inhibition of genes involved in fibrosis. (PMID:12707014)
• X-ray structure of human H-PGDS complexed with an inhibitor, 2-(2’-benzothiazolyl)-5-styryl-3-(4’-phthalhydrazidyl) tetrazolium chloride (BSPT) at 1.9 A resolution in the presence of Mg(2+). (PMID:15113825)
• single nucleotide polymorphism association with asthma in children in Japan (PMID:18946232)
• PU.1 cooperates with MAPK-activated cJun to maximally induce L-PGDS expression in macrophages. (PMID:19181746)
• Results describe the activation by Mg++ of human hematopoietic prostaglandin D(2) synthase, using Raman spectroscopy. (PMID:20074808)
• In patients with mixed atrophy, testicular mast cell numbers and phenotypes change with respect to the ability to express COX2 and PGDS-H. (PMID:21683347)
• the Val187Ile HPGDS isoenzyme common among African Americans is not associated with colorectal cancer risk (PMID:21821144)
• COX-1 and H-PGDS were rapidly ubiquitinated and degraded through the ubiquitin-proteasome system in response to the elevation of the intracellular calcium level (PMID:22049022)
• The effect of C. molle alkaloid extract on H-PGDS was studied. The alkaloid extract exhibited a 70% inhibition on H-PGDS with an IC50 of 13.7 mug/ml. (PMID:24996417)
• we have utilized a broad-scaled affinity proteomics approach to identify three proteins (CCL5, HPGDS, and NPSR1) with altered plasma levels in asthmatic children compared to healthy controls, representing the first evaluation of HPGDS and NPSR1 in plasma. (PMID:27145233)
• the development of a competition binding assay amenable to high-throughput screening (HTS) in a scintillation proximity assay (SPA) format. This assay was used to screen an in-house compound library of approximately 280,000 compounds for novel H-PGDS inhibitors. (PMID:27485270)
• Hematopoietic Prostaglandin D Synthase Is Increased in Mast Cells and Pericytes in Autopsy Myocardial Specimens from Patients with Duchenne Muscular Dystrophy. (PMID:38339125)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hpgds	ENSMUSG00000029919
rattus_norvegicus	Hpgds	ENSRNOG00000006583
drosophila_melanogaster	GstS1	FBGN0010226
caenorhabditis_elegans		WBGENE00001768

Paralogs (11): GSTP1 (ENSG00000084207), GSTM1 (ENSG00000134184), GSTM5 (ENSG00000134201), GSTM3 (ENSG00000134202), GSTM4 (ENSG00000168765), GSTA4 (ENSG00000170899), GSTA3 (ENSG00000174156), GSTA5 (ENSG00000182793), GSTM2 (ENSG00000213366), GSTA1 (ENSG00000243955), GSTA2 (ENSG00000244067)

Protein

Protein identifiers

Hematopoietic prostaglandin D synthase — O60760 (reviewed: O60760)

Alternative names: GST class-sigma, Glutathione S-transferase, Glutathione-dependent PGD synthase, Glutathione-requiring prostaglandin D synthase, Prostaglandin-H2 D-isomerase

All UniProt accessions (2): A0A384P5J0, O60760

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional enzyme which catalyzes both the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation, and the conjugation of glutathione with a wide range of aryl halides and organic isothiocyanates. Also exhibits low glutathione-peroxidase activity towards cumene hydroperoxide.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in a number of megakaryocytic cell lines but not in platelets. Highly expressed in adipose tissue, macrophages and placenta. Also expressed at lower levels in lung, heart, lymph nodes, appendix, bone marrow and fetal liver.

Activity regulation. Prostaglandin PGD2 synthesis is stimulated by calcium and magnesium ions. One calcium or magnesium ion is bound between the subunits of the homodimer. The interactions with the protein are for the most part mediated via water molecules. Magnesium increases the affinity for glutathione, while calcium has no effect on the affinity for glutathione.

Cofactor. Glutathione is required for the prostaglandin D synthase activity.

Induction. By 12-O-tetradecanoylphorbol-13-acetate (TPA).

Similarity. Belongs to the GST superfamily. Sigma family.

RefSeq proteins (1): NP_055300* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004045	Glutathione_S-Trfase_N	Domain
IPR004046	GST_C	Domain
IPR010987	Glutathione-S-Trfase_C-like	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR036282	Glutathione-S-Trfase_C_sf	Homologous_superfamily
IPR040079	Glutathione_S-Trfase	Family
IPR050213	GST_superfamily	Family

Pfam: PF02798, PF14497

Enzyme classification (BRENDA):

• EC 2.5.1.18 — glutathione transferase (BRENDA: 178 organisms, 548 substrates, 680 inhibitors, 878 Km, 525 kcat entries)
• EC 5.3.99.2 — Prostaglandin-D synthase (BRENDA: 13 organisms, 69 substrates, 257 inhibitors, 43 Km, 19 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
1-CHLORO-2,4-DINITROBENZENE	0.0003–223.6	289
GLUTATHIONE	0.0002–532.43	253
GSH	0.0003–37.4	62
PROSTAGLANDIN H2	0.0005–0.0328	28
REDUCED GLUTATHIONE	0.017–11.4	24
ETHACRYNIC ACID	0.0001–2.43	19
CUMENE HYDROPEROXIDE	0.038–14.3	10
(+)-2-BROMO-3-(4-NITROPHENYL)PROPANOIC ACID	0.023–0.417	8
MONOCHLOROBIMANE	0.004–0.25	8
4-CHLORO-7-NITROBENZO-2-OXA-1,3-DIAZOLE	0.324–3.866	7
1-IODOHEXANE	0.009–0.059	6
ALACHLOR	0.042–7.23	6
PHENETHYL ISOTHIOCYANATE	0.0065–0.14	6
STYRENE 7,8-OXIDE	0.064–0.365	6
(5Z,13E)-(15S)-9ALPHA,11ALPHA-EPIDIOXY-15-HYDROX	0.0023–0.5	6

Catalyzed reactions (Rhea), 3 shown:

• prostaglandin H2 = prostaglandin D2 (RHEA:10600)
• RX + glutathione = an S-substituted glutathione + a halide anion + H(+) (RHEA:16437)
• 2-glyceryl-prostaglandin H2 = 2-glyceryl-prostaglandin D2 (RHEA:51232)

UniProt features (32 total): helix 13, strand 6, binding site 5, mutagenesis site 3, domain 2, chain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

30 structures.

PDB	Method	Resolution (Å)
7JR8	X-RAY DIFFRACTION	1.13
5YX1	X-RAY DIFFRACTION	1.39
2CVD	X-RAY DIFFRACTION	1.45
6N4E	X-RAY DIFFRACTION	1.65
5YWE	X-RAY DIFFRACTION	1.68
1IYH	X-RAY DIFFRACTION	1.7
4EDY	X-RAY DIFFRACTION	1.72
5YWX	X-RAY DIFFRACTION	1.74
4EE0	X-RAY DIFFRACTION	1.75
1IYI	X-RAY DIFFRACTION	1.8
6ZTC	X-RAY DIFFRACTION	1.84
4EC0	X-RAY DIFFRACTION	1.85
5AIS	X-RAY DIFFRACTION	1.85
7JR6	X-RAY DIFFRACTION	1.88
1V40	X-RAY DIFFRACTION	1.9
3EE2	X-RAY DIFFRACTION	1.91
2VCQ	X-RAY DIFFRACTION	1.95
2VCW	X-RAY DIFFRACTION	1.95
2VCZ	X-RAY DIFFRACTION	1.95
6W8H	X-RAY DIFFRACTION	1.97
3VI5	X-RAY DIFFRACTION	2
3VI7	X-RAY DIFFRACTION	2
4EDZ	X-RAY DIFFRACTION	2
5AIV	X-RAY DIFFRACTION	2.04
2VCX	X-RAY DIFFRACTION	2.1
3KXO	X-RAY DIFFRACTION	2.1
5AIX	X-RAY DIFFRACTION	2.1
2VD0	X-RAY DIFFRACTION	2.2
2VD1	X-RAY DIFFRACTION	2.25
6W58	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60760-F1	97.40	0.98

Functional residue map

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

Ligand- & substrate-binding residues (5): 8; 14; 39; 49–51; 63–64

Mutagenesis-validated functional residues (3):

Position	Phenotype
97	reduces pgd2 synthesis by 99%. loss of activation by calcium or magnesium ions.
93	loss of activation by calcium or magnesium ions.
96	increases pgd2 synthesis. loss of activation by calcium or magnesium ions.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-156590	Glutathione conjugation
R-HSA-2162123	Synthesis of Prostaglandins (PG) and Thromboxanes (TX)

MSigDB gene sets: 189 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_BEHAVIOR, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOMF_GLUTATHIONE_TRANSFERASE_ACTIVITY, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_FATTY_ACID_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, BASSO_HAIRY_CELL_LEUKEMIA_UP

GO Biological Process (12): prostaglandin metabolic process (GO:0006693), glutathione metabolic process (GO:0006749), signal transduction (GO:0007165), locomotory behavior (GO:0007626), response to nematode (GO:0009624), response to selenium ion (GO:0010269), cyclooxygenase pathway (GO:0019371), negative regulation of male germ cell proliferation (GO:2000255), prostaglandin biosynthetic process (GO:0001516), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), fatty acid biosynthetic process (GO:0006633)

GO Molecular Function (9): magnesium ion binding (GO:0000287), glutathione transferase activity (GO:0004364), prostaglandin-D synthase activity (GO:0004667), calcium ion binding (GO:0005509), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), transferase activity (GO:0016740), isomerase activity (GO:0016853), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
Arachidonate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
metal ion binding	2
catalytic activity	2
prostanoid metabolic process	1
modified amino acid metabolic process	1
sulfur compound metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
behavior	1
response to other organism	1
response to chemical	1
prostaglandin biosynthetic process	1
arachidonate metabolic process	1
male germ cell proliferation	1
negative regulation of germ cell proliferation	1
negative regulation of reproductive process	1
regulation of male germ cell proliferation	1
prostaglandin metabolic process	1
prostanoid biosynthetic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
intramolecular oxidoreductase activity	1
identical protein binding	1
protein dimerization activity	1
binding	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1956 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HPGDS	SLCO6A1	Q86UG4	972
HPGDS	GSTK1	Q9Y2Q3	948
HPGDS	GSTZ1	O43708	929
HPGDS	PTGDS	P41222	911
HPGDS	GSTT2B	P0CG30	888
HPGDS	GSTO1	P78417	871
HPGDS	GLRX	P35754	854
HPGDS	GSTO2	Q9H4Y5	812
HPGDS	MGST1	P10620	759
HPGDS	EEF1G	P26641	740
HPGDS	MGST2	Q99735	740
HPGDS	B3GAT2	Q9NPZ5	717
HPGDS	GPX2	P18283	713
HPGDS	PPIG	Q13427	712
HPGDS	GPX7	Q96SL4	698

IntAct

28 interactions, top by confidence:

A	B	Type	Score
HPGDS	ARRDC3	psi-mi:“MI:0915”(physical association)	0.720
ARRDC3	HPGDS	psi-mi:“MI:0915”(physical association)	0.720
HPGDS	ABHD17A	psi-mi:“MI:0915”(physical association)	0.670
ABHD17A	HPGDS	psi-mi:“MI:0915”(physical association)	0.670
HPGDS	MELTF	psi-mi:“MI:0915”(physical association)	0.560
MELTF	HPGDS	psi-mi:“MI:0915”(physical association)	0.560
HPGDS	SIX6OS1	psi-mi:“MI:0915”(physical association)	0.560
HPGDS	LIF	psi-mi:“MI:0915”(physical association)	0.560
HPGDS	PDE3B	psi-mi:“MI:0915”(physical association)	0.560
HPGDS	CPNE3	psi-mi:“MI:0915”(physical association)	0.400
MELTF	HPGDS	psi-mi:“MI:0915”(physical association)	0.370
HPGDS	SIX6OS1	psi-mi:“MI:0915”(physical association)	0.000
LIF	HPGDS	psi-mi:“MI:0915”(physical association)	0.000
HPGDS	PDE3B	psi-mi:“MI:0915”(physical association)	0.000
ARRDC3	HPGDS	psi-mi:“MI:0915”(physical association)	0.000
HPGDS	ARRDC3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): HPGDS (Two-hybrid), ARRDC3 (Two-hybrid), ABHD17A (Two-hybrid), HPGDS (Co-crystal Structure), HPGDS (Two-hybrid), HPGDS (Two-hybrid), HPGDS (Two-hybrid), C14orf39 (Two-hybrid), CPNE3 (Proximity Label-MS), RPS18 (Cross-Linking-MS (XL-MS)), HPGDS (Co-crystal Structure)

ESM2 similar proteins: F4IA73, O15217, O16115, O18879, O35543, O60760, P00502, P04903, P04904, P08263, P09210, P09792, P10648, P13745, P14942, P24472, P26624, P26697, P30113, P30114, P30115, P32111, P46418, P46429, P46434, P51781, P80894, P81706, Q08392, Q08393, Q08862, Q08863, Q09607, Q16772, Q28035, Q54QV7, Q556G3, Q5E9G0, Q6AXY0, Q7RTV2

Diamond homologs: O16115, O16116, O18598, O35543, O60760, O73888, P04904, P08263, P10299, P10648, P13745, P14942, P15626, P18425, P24472, P26697, P27009, P27011, P27014, P27016, P30115, P41043, P46088, P46409, P46418, P46427, P46428, P46429, P46434, P46436, P46437, P48774, P80894, P81706, P91252, P91253, P91254, Q08862, Q09596, Q09607

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	2
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

930 predictions. Top by Δscore:

Variant	Effect	Δscore
4:94308632:A:AC	donor_gain	1.0000
4:94308633:C:CC	donor_gain	1.0000
4:94308636:T:A	donor_gain	1.0000
4:94317967:T:C	acceptor_gain	1.0000
4:94334489:CTACT:C	donor_loss	1.0000
4:94334490:TACTT:T	donor_loss	1.0000
4:94334491:ACTTA:A	donor_loss	1.0000
4:94334492:CT:C	donor_loss	1.0000
4:94334493:TTA:T	donor_loss	1.0000
4:94334494:TAC:T	donor_loss	1.0000
4:94334495:A:AC	donor_gain	1.0000
4:94334496:C:CT	donor_gain	1.0000
4:94334496:CTTGA:C	donor_gain	1.0000
4:94334634:CAATT:C	acceptor_gain	1.0000
4:94334637:TT:T	acceptor_gain	1.0000
4:94339227:ATTT:A	donor_gain	1.0000
4:94342790:CTTA:C	donor_loss	1.0000
4:94302144:A:AC	donor_gain	0.9900
4:94302145:C:CC	donor_gain	0.9900
4:94308633:CTT:C	donor_gain	0.9900
4:94308634:TTT:T	donor_gain	0.9900
4:94308635:TTC:T	donor_gain	0.9900
4:94317966:C:CC	acceptor_gain	0.9900
4:94317967:T:TC	acceptor_gain	0.9900
4:94334496:CT:C	donor_gain	0.9900
4:94334496:CTT:C	donor_gain	0.9900
4:94334496:CTTG:C	donor_gain	0.9900
4:94334635:AATT:A	acceptor_gain	0.9900
4:94334635:AATTC:A	acceptor_loss	0.9900
4:94334636:ATT:A	acceptor_gain	0.9900

AlphaMissense

1322 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:94299623:A:G	W153R	0.986
4:94299623:A:T	W153R	0.986
4:94334575:G:T	R19S	0.984
4:94299638:A:G	W148R	0.978
4:94299638:A:T	W148R	0.978
4:94317938:A:G	L54S	0.978
4:94317907:G:C	S64R	0.977
4:94317907:G:T	S64R	0.977
4:94317909:T:G	S64R	0.977
4:94308702:C:G	A90P	0.975
4:94334603:A:C	F9L	0.975
4:94334603:A:T	F9L	0.975
4:94334605:A:G	F9L	0.975
4:94299520:A:T	V187D	0.974
4:94334513:C:A	W39C	0.973
4:94334513:C:G	W39C	0.973
4:94334583:T:A	E16V	0.973
4:94334574:C:G	R19P	0.972
4:94317892:T:A	R69S	0.971
4:94317892:T:G	R69S	0.971
4:94334588:T:A	R14S	0.970
4:94334588:T:G	R14S	0.970
4:94334515:A:G	W39R	0.969
4:94334515:A:T	W39R	0.969
4:94299609:A:C	S157R	0.968
4:94299609:A:T	S157R	0.968
4:94299611:T:G	S157R	0.968
4:94334539:C:G	D31H	0.968
4:94308686:A:G	L95P	0.967
4:94299538:A:T	V181D	0.966

dbSNP variants (sampled 300 via entrez): RS1000055882 (4:94314992 G>A,T), RS1000253701 (4:94319719 A>G), RS1000281622 (4:94319914 C>A), RS1000483679 (4:94323914 A>C,G), RS1000533064 (4:94315183 C>T), RS1000622771 (4:94324811 G>A), RS1000623560 (4:94318832 C>T), RS1000644347 (4:94318839 A>G), RS1000717812 (4:94327612 C>T), RS1000771555 (4:94322993 T>G), RS1000818810 (4:94302008 T>G), RS1000851970 (4:94333431 T>A), RS1000901241 (4:94301012 A>G), RS1000994309 (4:94342359 A>T), RS10010986 (4:94322033 T>C,G)

Disease associations

OMIM: gene MIM:602598 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002023_3	Testicular germ cell tumor	1.000000e-08
GCST004029_27	Angiotensin-converting enzyme inhibitor intolerance	8.000000e-07
GCST004635_9	Testicular germ cell tumor	3.000000e-08
GCST004713_17	Testicular germ cell tumor	1.000000e-06
GCST006585_1676	Blood protein levels	4.000000e-59

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005325	response to angiotensin-converting enzyme inhibitor

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4680047 (PROTEIN-PROTEIN INTERACTION), CHEMBL4680054 (PROTEIN-PROTEIN INTERACTION), CHEMBL5879 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 12,365 (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
CHEMBL415324	TRANILAST	3	12,365

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

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
TFC007	Inhibition	7.08	pIC50
HQL-79	Inhibition	5.5	pIC50

Binding affinities (BindingDB)

172 measured of 207 human assays (208 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
NSC_5311503	KI	0.3 nM
NSC_3080928	KI	0.4 nM
CAS_41598-07-6	KI	1.7 nM
2-(6-fluoro-3-methylindazol-1-yl)-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]pyrimidine-5-carboxamide	IC50	3 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
2-[3-(difluoromethyl)indazol-1-yl]-N-[4-(3-methylsulfonylpropoxy)cyclohexyl]pyrimidine-5-carboxamide	IC50	3 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
US20250195518, Example 24	IC50	3 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
US20250195518, Example 55	IC50	3 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
US20250195518, Example 19	IC50	4 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
N-[4-(2-hydroxy-2-methylpropoxy)cyclohexyl]-2-(3-methylindazol-1-yl)pyrimidine-5-carboxamide	IC50	5 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
US20250195518, Example 128	IC50	5 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
5-[2-(1-benzylpiperidin-4-yl)-1H-imidazol-5-yl]-2-phenylpyrimidine	IC50	6 nM	US-9126973: Multiheteroaryl compounds as inhibitors of H-PGDS and their use for treating prostaglandin D2 mediated diseases
US20250195518, Example 40	IC50	7 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
US20250195518, Example 255	IC50	7 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
US20250195518, Example 46	IC50	10 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
N-[(1S)-1-[3-[5-(2-hydroxypropan-2-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]-2-pyridin-2-ylpyrimidine-5-carboxamide	IC50	11 nM	US-9469627: Phenyloxadiazole derivatives as PGDS inhibitors
2-(6-fluoro-3-methylindazol-1-yl)-N-[3-(2-hydroxypropan-2-yl)-1-bicyclo[1.1.1]pentanyl]pyrimidine-5-carboxamide	IC50	11 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
2-phenyl-5-(2-phenyl-1H-imidazol-5-yl)pyrimidine	IC50	12 nM	US-9126973: Multiheteroaryl compounds as inhibitors of H-PGDS and their use for treating prostaglandin D2 mediated diseases
N-[[3-[5-(2-hydroxypropan-2-yl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-2-pyridin-2-ylpyrimidine-5-carboxamide	IC50	12 nM	US-9469627: Phenyloxadiazole derivatives as PGDS inhibitors
US20250195518, Example 15	IC50	12 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
2-[3-(difluoromethyl)pyrazolo[5,4-c]pyridin-1-yl]-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]pyrimidine-5-carboxamide	IC50	13 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
US20250195518, Example 150	IC50	14 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
US20250195518, Example 173	IC50	14 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
US20250195518, Example 196	IC50	14 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
US20250195518, Example 204	IC50	14 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
US20250195518, Example 254	IC50	14 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
4-(5-methylcyclopenta-1,3-diene-1-carbonyl)-N-[1-[4-[2-(triazol-1-yl)ethyl]phenyl]piperidin-4-yl]piperazine-1-carboxamide	IC50	15 nM	US-8765750: Piperazine compound having a PGDS inhibitory effect
US20250195518, Example 80	IC50	17 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
2-phenyl-5-(2-pyridin-3-yl-1H-imidazol-5-yl)pyrimidine	IC50	21 nM	US-9126973: Multiheteroaryl compounds as inhibitors of H-PGDS and their use for treating prostaglandin D2 mediated diseases
N-[4-(2-hydroxy-2-methylpropyl)cyclohexyl]-2-(3-methylpyrazolo[5,4-c]pyridin-1-yl)pyrimidine-5-carboxamide	IC50	21 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
US20250195518, Example 143	IC50	24 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
N-[(1R)-1-[3-[5-(2-hydroxypropan-2-yl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]-2-pyridin-2-ylpyrimidine-5-carboxamide	IC50	26 nM	US-9469627: Phenyloxadiazole derivatives as PGDS inhibitors
4-(5-methylcyclopenta-1,3-diene-1-carbonyl)-N-[1-[4-(2-morpholin-4-ylethylcarbamoyl)phenyl]piperidin-4-yl]piperazine-1-carboxamide	IC50	27 nM	US-8765750: Piperazine compound having a PGDS inhibitory effect
4-(5-methylcyclopenta-1,3-diene-1-carbonyl)-N-[1-[4-[3-(triazol-1-yl)propyl]phenyl]piperidin-4-yl]piperazine-1-carboxamide	IC50	27 nM	US-8765750: Piperazine compound having a PGDS inhibitory effect
US20250195518, Example 17	IC50	27 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
4-(5-methylcyclopenta-1,3-diene-1-carbonyl)-N-[1-[4-(morpholine-4-carbonyl)phenyl]piperidin-4-yl]piperazine-1-carboxamide	IC50	31 nM	US-8765750: Piperazine compound having a PGDS inhibitory effect
4-(1-methylpyrrole-2-carbonyl)-N-[4-[4-(piperidine-1-carbonyl)piperidin-1-yl]phenyl]piperazine-1-carboxamide	IC50	32 nM	US-8865714: Piperazine compound capable of inhibiting prostaglandin D synthase
4-(1-methylpyrrole-2-carbonyl)-N-[4-[4-[3-(triazol-1-yl)propyl]piperidin-1-yl]phenyl]piperazine-1-carboxamide	IC50	37 nM	US-8865714: Piperazine compound capable of inhibiting prostaglandin D synthase
4-(5-ethylcyclopenta-1,3-diene-1-carbonyl)-N-[1-[4-(2-morpholin-4-ylethylcarbamoyl)phenyl]piperidin-4-yl]piperazine-1-carboxamide	IC50	39 nM	US-8765750: Piperazine compound having a PGDS inhibitory effect
4-(1-methylpyrrole-2-carbonyl)-N-[4-[4-(2-pyrazol-1-ylethyl)piperidin-1-yl]phenyl]piperazine-1-carboxamide	IC50	40 nM	US-8865714: Piperazine compound capable of inhibiting prostaglandin D synthase
4-(5-methylcyclopenta-1,3-diene-1-carbonyl)-N-[1-[4-(piperidine-1-carbonyl)phenyl]piperidin-4-yl]piperazine-1-carboxamide	IC50	41 nM	US-8765750: Piperazine compound having a PGDS inhibitory effect
US20250195518, Example 54	IC50	41 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
US20250195518, Example 144	IC50	41 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
4-(1-methylpyrrole-2-carbonyl)-N-[4-[4-(2-morpholin-4-ylethyl)piperidin-1-yl]phenyl]piperazine-1-carboxamide	IC50	43 nM	US-8865714: Piperazine compound capable of inhibiting prostaglandin D synthase
US20250195518, Example 18	IC50	45 nM	US-20250195518: INDAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF
4-(1-methylpyrrole-2-carbonyl)-N-[4-[4-[3-(1,2,4-triazol-1-yl)propyl]piperidin-1-yl]phenyl]piperazine-1-carboxamide	IC50	46 nM	US-8865714: Piperazine compound capable of inhibiting prostaglandin D synthase
4-(5-methylcyclopenta-1,3-diene-1-carbonyl)-N-[1-[4-(pyrrolidine-1-carbonyl)phenyl]piperidin-4-yl]piperazine-1-carboxamide	IC50	52 nM	US-8765750: Piperazine compound having a PGDS inhibitory effect
4-(1-methylpyrrole-2-carbonyl)-N-[4-[4-(morpholin-4-ylmethyl)piperidin-1-yl]phenyl]piperazine-1-carboxamide	IC50	54 nM	US-8865714: Piperazine compound capable of inhibiting prostaglandin D synthase
N-[4-(4-hydroxypiperidin-1-yl)phenyl]-4-(1-methylpyrrole-2-carbonyl)piperazine-1-carboxamide	IC50	58 nM	US-8865714: Piperazine compound capable of inhibiting prostaglandin D synthase
4-(1-methylpyrrole-2-carbonyl)-N-[4-[4-(2-morpholin-4-ylethylcarbamoyl)piperidin-1-yl]phenyl]piperazine-1-carboxamide	IC50	59 nM	US-8865714: Piperazine compound capable of inhibiting prostaglandin D synthase
5-(2-benzyl-1H-imidazol-5-yl)-2-phenylpyrimidine	IC50	59 nM	US-9126973: Multiheteroaryl compounds as inhibitors of H-PGDS and their use for treating prostaglandin D2 mediated diseases

ChEMBL bioactivities

459 potent at pChembl≥5 of 507 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.73	EC50	0.0187	nM	CHEMBL5076100
10.62	EC50	0.0238	nM	CHEMBL5207946
10.56	EC50	0.0276	nM	CHEMBL5200341
10.15	EC50	0.0714	nM	CHEMBL5193611
9.85	Kd	0.14	nM	CHEMBL4238290
9.70	IC50	0.2	nM	CHEMBL2035650
9.62	Kd	0.24	nM	CHEMBL5285108
9.43	Kd	0.37	nM	CHEMBL4238186
9.30	Kd	0.5	nM	CHEMBL4473072
8.63	IC50	2.34	nM	CHEMBL2035651
8.62	IC50	2.4	nM	CHEMBL5272869
8.52	IC50	3	nM	CHEMBL4247050
8.51	IC50	3.1	nM	CHEMBL5289520
8.42	IC50	3.8	nM	CHEMBL5289730
8.41	IC50	3.9	nM	CHEMBL5279860
8.41	IC50	3.9	nM	CHEMBL5275536
8.41	IC50	3.9	nM	CHEMBL5282861
8.40	IC50	4	nM	CHEMBL3925567
8.36	IC50	4.4	nM	CHEMBL5285125
8.34	IC50	4.6	nM	CHEMBL5279371
8.34	IC50	4.6	nM	CHEMBL5266142
8.33	IC50	4.7	nM	CHEMBL5269778
8.32	IC50	4.8	nM	CHEMBL5269001
8.31	IC50	4.9	nM	CHEMBL5279720
8.30	IC50	5	nM	CHEMBL5278680
8.30	IC50	5	nM	CHEMBL5266618
8.29	IC50	5.1	nM	CHEMBL5267588
8.28	IC50	5.3	nM	CHEMBL5283521
8.23	IC50	5.88	nM	CHEMBL4752221
8.22	IC50	6	nM	CHEMBL3982640
8.22	IC50	6	nM	CHEMBL4241885
8.22	IC50	6	nM	CHEMBL4866146
8.19	IC50	6.4	nM	CHEMBL5282228
8.19	IC50	6.4	nM	CHEMBL5273656
8.18	IC50	6.6	nM	CHEMBL5277213
8.15	IC50	7	nM	CHEMBL3181890
8.15	IC50	7.14	nM	CHEMBL4740750
8.15	IC50	7.1	nM	CHEMBL5268479
8.14	IC50	7.18	nM	CHEMBL4753053
8.13	IC50	7.48	nM	CHEMBL3963991
8.10	IC50	8	nM	CHEMBL4250602
8.10	IC50	8	nM	CHEMBL4870703
8.09	IC50	8.2	nM	CHEMBL4439454
8.08	IC50	8.26	nM	CHEMBL2035653
8.07	IC50	8.5	nM	CHEMBL5289474
8.05	IC50	8.88	nM	CHEMBL3978032
8.05	IC50	9	nM	CHEMBL4864805
8.03	IC50	9.4	nM	CHEMBL5285108
8.02	Kd	9.5	nM	CHEMBL1233897
8.02	IC50	9.5	nM	CHEMBL4242281

PubChem BioAssay actives

326 with measured affinity, of 557 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
N-[4-[4-[4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]piperazine-1-carbonyl]piperidin-1-yl]phenyl]-2-phenoxypyrimidine-5-carboxamide	1858479: PROTAC activity at CRBN/H-PGDS in human KU812 cells assessed as reduction in H-PGDS levels incubated for 24 hrs by Western blotting analysis	ec50	<0.0001	uM
N-[4-[4-[4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]piperazine-1-carbonyl]piperidin-1-yl]phenyl]-2-phenoxypyrimidine-5-carboxamide	1858479: PROTAC activity at CRBN/H-PGDS in human KU812 cells assessed as reduction in H-PGDS levels incubated for 24 hrs by Western blotting analysis	ec50	<0.0001	uM
N-[4-[4-[4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]piperazine-1-carbonyl]piperidin-1-yl]phenyl]-4-(1-methylpyrrole-2-carbonyl)piperazine-1-carboxamide	1858479: PROTAC activity at CRBN/H-PGDS in human KU812 cells assessed as reduction in H-PGDS levels incubated for 24 hrs by Western blotting analysis	ec50	<0.0001	uM
N-[4-(2-oxopyrrolidin-1-yl)phenyl]-2-pyridin-2-ylpyrimidine-5-carboxamide	1399746: Binding affinity to full length recombinant human N-terminal His6-tagged H-PGDS expressed in Escherichia coli BL21(DE3) by SPR analysis	kd	0.0001	uM
N-[4-[4-[4-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]piperazine-1-carbonyl]piperidin-1-yl]phenyl]-4-(1-methylpyrrole-2-carbonyl)piperazine-1-carboxamide	1858479: PROTAC activity at CRBN/H-PGDS in human KU812 cells assessed as reduction in H-PGDS levels incubated for 24 hrs by Western blotting analysis	ec50	0.0001	uM
7-cyclopropyl-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]-1,8-naphthyridine-3-carboxamide	1961223: Binding affinity to human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as equilibrium dissociation constant by measuring changes in intrinsic tryptophan fluorescence in presence of glutathione by fluorescence based analysis	kd	0.0002	uM
6-phenyl-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]pyridine-3-carboxamide	665996: Inhibition of HPGDS	ic50	0.0002	uM
N-[4-[4-(morpholine-4-carbonyl)piperidin-1-yl]phenyl]-2-phenoxypyrimidine-5-carboxamide	1399746: Binding affinity to full length recombinant human N-terminal His6-tagged H-PGDS expressed in Escherichia coli BL21(DE3) by SPR analysis	kd	0.0004	uM
7-(difluoromethoxy)-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]quinoline-3-carboxamide	1603164: Binding affinity to full-length human His6-tagged HPGDS expressed in Escherichia coli BL21 (DE3) by tryptophan fluorescence quenching assay	kd	0.0005	uM
4-methyl-2-phenyl-N-(4-sulfamoylphenyl)-1,3-thiazole-5-carboxamide	665996: Inhibition of HPGDS	ic50	0.0010	uM
4-isoquinolin-1-yl-N-(2-morpholin-4-ylethyl)benzamide	665995: Inhibition of human recombinant HPGDS using PGH2 as substrate assessed as production of PGD2 preincubated for 10 mins prior substrate addition measured after 42 secs by TBA-based fluorescence assay	ic50	0.0023	uM
7-(azetidin-1-yl)-6-chloro-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0024	uM
N-(5-methoxy-3-methylpyrrolo[3,2-b]pyridin-1-yl)-4-methyl-2-pyridin-2-ylpyrimidine-5-carboxamide	1399575: Inhibition of HPGDS (unknown origin)	ic50	0.0030	uM
6-chloro-N-[3-(2-hydroxypropan-2-yl)cyclobutyl]-7-[(2S)-2-methylazetidin-1-yl]-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0031	uM
6-chloro-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]-7-[(2S)-2-methylazetidin-1-yl]-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0038	uM
6-chloro-7-cyclopropyl-N-[3-(2-hydroxypropan-2-yl)cyclobutyl]-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0039	uM
7-cyclopropyl-N-[6-(2-hydroxypropan-2-yl)spiro[3.3]heptan-2-yl]-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0039	uM
7-(azetidin-1-yl)-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]-1,6-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0039	uM
N-[4-(2-hydroxypropan-2-yl)cyclohexyl]-7-[(2S)-2-methylazetidin-1-yl]-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0044	uM
6-chloro-7-cyclopropyl-N-[(3S)-2-oxopyrrolidin-3-yl]-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0046	uM
6-chloro-N-(4-hydroxy-4-methylcyclohexyl)-7-[(2S)-2-methylazetidin-1-yl]-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0046	uM
6-chloro-7-cyclopropyl-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0047	uM
N-[4-(2-hydroxypropan-2-yl)cyclohexyl]-7-[(2S)-2-methylazetidin-1-yl]-1,6-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0048	uM
6-chloro-N-(3-hydroxy-3-methylcyclobutyl)-7-[(2S)-2-methylazetidin-1-yl]-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0050	uM
6-chloro-7-[(2S)-2-methylazetidin-1-yl]-N-[(3S)-2-oxopyrrolidin-3-yl]-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0051	uM
7-(azetidin-1-yl)-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0053	uM
2-[3-[3-[5-(2-phenylpyrimidin-5-yl)-1H-imidazol-2-yl]phenyl]-1,2,4-oxadiazol-5-yl]propan-2-ol	1719065: Inhibition of HPGDS (unknown origin) by fluorescence polarization assay	ic50	0.0059	uM
1-(3-fluorophenyl)-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]indazole-5-carboxamide	1776843: Inhibition of human HPGDS assessed as reduction in PGD2 formation using PGH2 as substrate by mass spectrometry	ic50	0.0060	uM
N-(5-fluoro-3-methylpyrrolo[3,2-b]pyridin-1-yl)-4-methyl-2-pyridin-2-ylpyrimidine-5-carboxamide	1399575: Inhibition of HPGDS (unknown origin)	ic50	0.0060	uM
2-cyclopropyl-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]pyrido[2,3-d]pyrimidine-6-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0064	uM
6-chloro-7-cyclopropyl-N-(3-hydroxy-3-methylcyclobutyl)-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0064	uM
6-chloro-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]-7-methoxy-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0066	uM
N-(5-fluoro-3-methylindol-1-yl)-4-methyl-2-pyridin-2-ylpyrimidine-5-carboxamide	1399575: Inhibition of HPGDS (unknown origin)	ic50	0.0070	uM
N-benzyl-2-pyridin-2-ylpyrimidine-5-carboxamide	1719065: Inhibition of HPGDS (unknown origin) by fluorescence polarization assay	ic50	0.0071	uM
N-[[3-[5-(2-hydroxypropan-2-yl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-2-phenylpyrimidine-5-carboxamide	1719065: Inhibition of HPGDS (unknown origin) by fluorescence polarization assay	ic50	0.0072	uM
N-[[3-[5-(2-hydroxypropan-2-yl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-2-pyridin-2-ylpyrimidine-5-carboxamide	1719065: Inhibition of HPGDS (unknown origin) by fluorescence polarization assay	ic50	0.0075	uM
4-methyl-2-pyrimidin-2-yl-N-[4-(trifluoromethyl)indol-1-yl]pyrimidine-5-carboxamide	1399575: Inhibition of HPGDS (unknown origin)	ic50	0.0080	uM
2-(2-fluorophenyl)-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]imidazo[1,2-a]pyridine-6-carboxamide	1776843: Inhibition of human HPGDS assessed as reduction in PGD2 formation using PGH2 as substrate by mass spectrometry	ic50	0.0080	uM
N-[6-(2-hydroxypropan-2-yl)spiro[3.3]heptan-2-yl]-7-methoxyquinoline-3-carboxamide	1603153: Inhibition of full-length human His6-tagged HPGDS expressed in Escherichia coli BL21 (DE3) using PGH2 as substrate measured after 90 to 120 secs by RapidFire high-throughput mass spectrometry assay	ic50	0.0082	uM
4-(3-methylisoquinolin-1-yl)-N-(2-morpholin-4-ylethyl)benzamide	665995: Inhibition of human recombinant HPGDS using PGH2 as substrate assessed as production of PGD2 preincubated for 10 mins prior substrate addition measured after 42 secs by TBA-based fluorescence assay	ic50	0.0083	uM
N-[4-(2-hydroxypropan-2-yl)cyclohexyl]-7-propan-2-yl-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0085	uM
2-phenyl-5-(2-phenyl-1H-imidazol-5-yl)pyrimidine	1719065: Inhibition of HPGDS (unknown origin) by fluorescence polarization assay	ic50	0.0089	uM
N-[4-(2-hydroxypropan-2-yl)cyclohexyl]-2-phenylimidazo[1,2-a]pyridine-6-carboxamide	1776843: Inhibition of human HPGDS assessed as reduction in PGD2 formation using PGH2 as substrate by mass spectrometry	ic50	0.0090	uM
2-(3-fluorophenyl)-4-methyl-N-[[3-(methylsulfamoyl)phenyl]methyl]pyrimidine-5-carboxamide	1399575: Inhibition of HPGDS (unknown origin)	ic50	0.0095	uM
6-(3-fluorophenyl)-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]pyridine-3-carboxamide	1204702: Binding affinity to human HPGDS expressed in Escherichia coli using 1-phenylpyrazole-4-carboxylic acid/6-(3-fluorophenyl)pyridine-3-carboxamide as reporter probe by ligand-observed 1D NMR T1rho binding assay	kd	0.0095	uM
7-methoxy-N-[1-(1,3-thiazol-2-yl)piperidin-4-yl]quinoline-3-carboxamide	1603153: Inhibition of full-length human His6-tagged HPGDS expressed in Escherichia coli BL21 (DE3) using PGH2 as substrate measured after 90 to 120 secs by RapidFire high-throughput mass spectrometry assay	ic50	0.0097	uM
7-cyclobutyl-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0100	uM
4-methyl-2-pyridin-2-yl-N-[4-(trifluoromethyl)indol-1-yl]pyrimidine-5-carboxamide	1399575: Inhibition of HPGDS (unknown origin)	ic50	0.0100	uM
1-(3-fluorophenyl)-N-[4-(2-hydroxypropan-2-yl)cyclohexyl]indole-5-carboxamide	1776843: Inhibition of human HPGDS assessed as reduction in PGD2 formation using PGH2 as substrate by mass spectrometry	ic50	0.0100	uM
7-cyclopropyl-N-[4-(1,1-difluoropropan-2-ylamino)cyclohexyl]-1,8-naphthyridine-3-carboxamide	1961202: Inhibition of human H-PGDS expressed in Escherichia coli BL21 DE3 cells assessed as reduction in PGD2 production using PGH2 as substrate by RapidFire High Throughput Mass spectrometry	ic50	0.0110	uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, decreases methylation, increases expression	2
2,4,6-tribromophenol	decreases expression	1
sanguinarine	decreases activity	1
bisphenol A	affects cotreatment, increases methylation	1
decabromobiphenyl ether	decreases expression	1
oxyfluorofen	affects binding	1
sulforaphane	decreases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	increases phosphorylation	1
pencycuron	affects binding	1
pentanal	increases expression	1
acifluorfen-methyl	affects binding	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Dichlorodiphenyl Dichloroethylene	affects binding	1
Erythrosine	decreases activity	1
Formaldehyde	increases expression	1
Iron	increases expression	1
Isoquinolines	affects binding, decreases activity, affects reaction	1
Suramin	decreases activity	1
Tobacco Smoke Pollution	decreases expression	1
Water	decreases activity, affects binding, affects reaction	1
Particulate Matter	decreases expression	1

ChEMBL screening assays

90 unique, capped per target: 89 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4679897	Binding	SNIPER activity at IAP1/HPGDS in human KU812 cells assessed as reduction in HPGDS protein level up to 1000 nM measured after 6 hrs by Western blot analysis	Development of a Hematopoietic Prostaglandin D Synthase-Degradation Inducer. — ACS Med Chem Lett
CHEMBL1743242	ADMET	Substrates for human cytosolic glutathione transferase PGDS	Casarett and Doull’s Toxicology The Basic Science of Poisons, 7th edition

Clinical trials (associated diseases)

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