PDE3A

Summary

PDE3A (phosphodiesterase 3A, HGNC:8778) is a protein-coding gene on chromosome 12p12.2, encoding cGMP-inhibited 3’,5’-cyclic phosphodiesterase 3A (Q14432). Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.

This gene encodes a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (cGI-PDE) family. cGI-PDE enzymes hydrolyze both cAMP and cGMP, and play critical roles in many cellular processes by regulating the amplitude and duration of intracellular cyclic nucleotide signals. The encoded protein mediates platelet aggregation and also plays important roles in cardiovascular function by regulating vascular smooth muscle contraction and relaxation. Inhibitors of the encoded protein may be effective in treating congestive heart failure. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 5139 — RefSeq curated summary.

At a glance

• Gene–disease (curated): brachydactyly-arterial hypertension syndrome (Strong, GenCC)
• GWAS associations: 68
• Clinical variants (ClinVar): 336 total — 7 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes — 162 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000921

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8778
Approved symbol	PDE3A
Name	phosphodiesterase 3A
Location	12p12.2
Locus type	gene with protein product
Status	Approved
Aliases	CGI-PDE
Ensembl gene	ENSG00000172572
Ensembl biotype	protein_coding
OMIM	123805
Entrez	5139

Gene structure

Transcript identifiers

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

ENST00000359062, ENST00000542675, ENST00000544307, ENST00000951762

RefSeq mRNA: 5 — MANE Select: NM_000921 NM_000921, NM_001244683, NM_001378407, NM_001378408, NM_001378409

CCDS: CCDS31754

Canonical transcript exons

ENST00000359062 — 16 exons

Exon	Start	End
ENSE00001197033	20556660	20556710
ENSE00001248317	20368537	20370244
ENSE00002288644	20680030	20688583
ENSE00003483637	20646490	20646603
ENSE00003499330	20639846	20639957
ENSE00003510563	20613443	20613700
ENSE00003518916	20650445	20650600
ENSE00003519456	20616230	20616384
ENSE00003542591	20634902	20635056
ENSE00003549099	20653947	20654205
ENSE00003577466	20637100	20637237
ENSE00003628180	20646751	20646950
ENSE00003648725	20629908	20630127
ENSE00003659331	20621296	20621411
ENSE00003660541	20648688	20648891
ENSE00003686917	20633693	20633778

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 98.91.

FANTOM5 (CAGE): breadth broad, TPM avg 4.7129 / max 261.8869, expressed in 850 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124622	1.4249	552
124628	1.1901	378
124633	0.6048	241
124627	0.2569	105
124625	0.2506	78
124629	0.2386	91
124630	0.2177	90
124632	0.1395	65
124624	0.1296	69
124631	0.1132	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	98.91	gold quality
vena cava	UBERON:0004087	91.24	gold quality
cardiac ventricle	UBERON:0002082	91.12	gold quality
heart left ventricle	UBERON:0002084	90.94	gold quality
myocardium	UBERON:0002349	90.39	gold quality
heart	UBERON:0000948	89.54	gold quality
popliteal artery	UBERON:0002250	89.06	gold quality
tibial artery	UBERON:0007610	89.04	gold quality
descending thoracic aorta	UBERON:0002345	88.06	gold quality
right coronary artery	UBERON:0001625	87.50	gold quality
aorta	UBERON:0000947	87.47	gold quality
cardiac atrium	UBERON:0002081	86.95	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.93	gold quality
right atrium auricular region	UBERON:0006631	86.62	gold quality
left ventricle myocardium	UBERON:0006566	86.36	gold quality
urethra	UBERON:0000057	86.27	gold quality
colonic epithelium	UBERON:0000397	85.99	gold quality
left coronary artery	UBERON:0001626	85.52	gold quality
apex of heart	UBERON:0002098	85.43	gold quality
thoracic aorta	UBERON:0001515	85.35	gold quality
colonic mucosa	UBERON:0000317	85.06	gold quality
oocyte	CL:0000023	85.05	gold quality
coronary artery	UBERON:0001621	85.03	gold quality
ascending aorta	UBERON:0001496	84.99	gold quality
rectum	UBERON:0001052	84.93	gold quality
islet of Langerhans	UBERON:0000006	84.80	gold quality
mucosa of stomach	UBERON:0001199	84.61	gold quality
parotid gland	UBERON:0001831	84.41	gold quality
mucosa of sigmoid colon	UBERON:0004993	84.41	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.82	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	3126.99
E-CURD-119	yes	2541.82
E-HCAD-10	yes	54.04
E-MTAB-5061	yes	13.37
E-HCAD-35	yes	8.78
E-GEOD-81608	yes	7.44
E-ANND-3	yes	7.29
E-MTAB-11268	no	4047.37

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREM, GATA3, THRA

miRNA regulators (miRDB)

186 targeting PDE3A, 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-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-5688	99.96	73.23	4504

Literature-anchored findings (GeneRIF, showing 38)

• There was a concentration-dependent inhibition in the increase of intracellular Ca2+ with PDE3 inhibition and significantly less with PDE2 inhibition. (PMID:12038792)
• These findings suggest that alternative processing of the PDE3A gene results in the generation of two mRNAs and three protein isoforms in cardiac myocytes that differ in intracellular localization and may be regulated through different signaling pathways. (PMID:12154085)
• PDE3A gene transcript levels are increased in the intrapulmonary and resistance pulmonary arteries by chronic hypoxia. (PMID:12466227)
• Presence of phosphodiesterase type 3 A (PDE 3A) mRNA was confirmed in human germinal vesicle-stage (GV) oocytes. A selective PDE 3 inhibitor, Org 9935, arrested oocytes retrieved from immature follicles in prophase I for up to 72 h. (PMID:12773402)
• PDE3, but not of PDE5, extends to all major processes in thrombus formation: assembly of platelets into aggregates, secretion of autocrine products, and procoagulant activity. (PMID:15041473)
• 14-3-3 Proteins can discriminate between sites in a region of multisite phosphorylation on PDE3A; the cytoskeletal cross-linker protein plectin-1 coimmunoprecipitated with PDE3A independently of 14-3-3 binding. (PMID:16153182)
• cGMP may amplify cAMP-mediated signaling in intracellular compartments of myocardium by PDE3-dependent and PDE3-independent mechanisms. (PMID:16172121)
• structure-function analysis of the catalytic region of human platelet phosphodiesterase 3A (PMID:16873361)
• The positive-feedback loop described in this review is regulated by phosphodiesterase 3A and inducible cAMP early repressor (ICER) and is pathologically important in adult hearts. (PMID:17332439)
• activation/phosphorylation of PDE3A via Akt signaling pathway participates in regulating cAMP during thrombin activation of platelets. (PMID:17392505)
• platelet activation stimulates PKC-dependent phosphorylation of PDE3A on Ser(312), Ser(428), Ser(438), Ser(465), and Ser(492) leading to a subsequent increase in cAMP hydrolysis and 14-3-3 binding. (PMID:19261611)
• Data show that PDE3A inhibition augments CFTR-dependent submucosal gland secretion and actin skeleton disruption decreases secretion. (PMID:20089840)
• Anagrelide suppresses megakaryocytopoiesis by reducing the expression levels of GATA-1 and FOG-1 via a PDEIII-independent mechanism that is differentiation context-specific and does not involve inhibition of MPL-mediated early signal transduction events (PMID:20586925)
• PI3Kgamma coordinates the coincident signaling of the major cardiac PDE3 and PDE4 isoforms, thus orchestrating a feedback loop that prevents calcium-dependent ventricular arrhythmia. (PMID:23008439)
• The PDE3A-SLCO1C1 locus rs3794271 SNP showed a highly significant association with anti-TNF treatment response. (PMID:23651021)
• the genotypic and allelic frequencies of the rs7134375 SNP are different between the Mulao and Han populations. the PDE3A rs7134375 SNP is associated with serum TG levels in the Mulao population, however, not in the Han population. (PMID:24604378)
• We found a highly significant association between PDE3A-SLCO1C1 and the clinical response to TNF blockers (PMID:25403996)
• PDE3A is part of a SERCA2 signaling complex in cardiac myocytes. (PMID:25593322)
• A heterozygous missense mutation in PDE3A causes autosomal dominant hypertension with brachydactyly. (PMID:25961942)
• Epigenetic regulation of phosphodiesterases 2A and 3A underlies compromised beta-adrenergic Signaling in an induced pluripotent stem cell model of dilated cardiomyopathy. (PMID:26095046)
• Chemical proteomics results show that besides known interactors such as 14-3-3 family proteins, PDE3A was found to associate with a PP2A complex composed of a regulatory, scaffold and catalytic subunit. (PMID:26205238)
• We found a novel heterozygous missense mutation c.1336T>C in exon 4 of the PDE3A gene in a Japanese family with multiple HTNB patients. This mutation was found to be completely linked to the family members who inherited this condition. (PMID:27053290)
• The genetic variant, rs3794271, located within the PDE3A-SLCO1C1 locus was analyzed for correlation with treatment response using both the EULAR classification criteria and absolute change in (Delta)DAS28 scores as outcome measures correlated with anti-TNF response in a large UK rheumatoid arthritis cohort. (PMID:27180831)
• PDE3A is a low-affinity and high-velocity enzyme for hydrolysis of cUMP in cardiac myocytes. (PMID:27975297)
• PDE3A is downregulated in chemoresistant NSCLC cells due to DNA hypermethylation. (PMID:28678321)
• Vulnerability to antineoplastic phosphodiesterase inhibitors inhibitors has been associated with co-expression of PDE3A and SLFN12 in various tumor types. (PMID:29107068)
• PDE3A-related miRNAs miR-221/miR-222 and miR-27a/miR-27b/miR-128 are potentially linked to pathways essential for immune regulation as well as cerebral and vascular integrity/function. (PMID:30603956)
• Influence of Genetic Variation in PDE3A on Endothelial Function and Stroke. (PMID:31865795)
• Phosphodiesterase 3A Represents a Therapeutic Target that Drives Stem Cell-like Property and Metastasis in Breast Cancer. (PMID:31871268)
• Nitric oxide activates AMPK by modulating PDE3A in human pulmonary artery smooth muscle cells. (PMID:32914566)
• Impact of phosphodiesterases PDE3 and PDE4 on 5-hydroxytryptamine receptor4-mediated increase of cAMP in human atrial fibrillation. (PMID:32949251)
• Identification and functional study of genetic polymorphisms in cyclic nucleotide phosphodiesterase 3A (PDE3A). (PMID:33249558)
• Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase. (PMID:34272366)
• Mutant Phosphodiesterase 3A Protects From Hypertension-Induced Cardiac Damage. (PMID:36259389)
• Disruption of Phosphodiesterase 3A Binding to SERCA2 Increases SERCA2 Activity and Reduces Mortality in Mice With Chronic Heart Failure. (PMID:36876489)
• Mutations in Phosphodiesterase 3A (PDE3A) Cause Hypertension Without Cardiac Damage. (PMID:37035914)
• Mutant phosphodiesterase 3A protects the kidney from hypertension-induced damage. (PMID:37244472)
• ALDOA coordinates PDE3A through the beta-catenin/ID3 axis to stimulate cancer metastasis and M2 polarization in lung cancer with EGFR mutations. (PMID:38244313)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	pde3a	ENSDARG00000004227
mus_musculus	Pde3a	ENSMUSG00000041741
rattus_norvegicus	Pde3a	ENSRNOG00000025042
drosophila_melanogaster	Pde11	FBGN0085370
drosophila_melanogaster	Pde8	FBGN0266377
caenorhabditis_elegans		WBGENE00008443
caenorhabditis_elegans	pde-6	WBGENE00022389

Paralogs (20): PDE4A (ENSG00000065989), PDE8A (ENSG00000073417), PDE6C (ENSG00000095464), PDE4C (ENSG00000105650), PDE10A (ENSG00000112541), PDE8B (ENSG00000113231), PDE4D (ENSG00000113448), PDE1A (ENSG00000115252), PDE1B (ENSG00000123360), PDE11A (ENSG00000128655), PDE6A (ENSG00000132915), PDE6B (ENSG00000133256), PDE5A (ENSG00000138735), PDE3B (ENSG00000152270), PDE1C (ENSG00000154678), PDE9A (ENSG00000160191), PDE7B (ENSG00000171408), PDE4B (ENSG00000184588), PDE2A (ENSG00000186642), PDE7A (ENSG00000205268)

Protein

Protein identifiers

cGMP-inhibited 3’,5’-cyclic phosphodiesterase 3A — Q14432 (reviewed: Q14432)

Alternative names: Cyclic GMP-inhibited phosphodiesterase A, cGMP-inhibited cAMP phosphodiesterase

All UniProt accessions (1): Q14432

UniProt curated annotations — full annotation on UniProt →

Function. Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Also has activity toward cUMP. Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling.

Subunit / interactions. Homodimer. Interacts with SLFN12; direct low affinity interaction which is stimulated by binding of 17beta-estradiol/E2 to PDE3A and that positively regulates the ribonuclease activity of SLFN12.

Subcellular location. Membrane. Cytoplasm. Cytosol.

Disease relevance. Hypertension and brachydactyly syndrome (HTNB) [MIM:112410] A syndrome characterized by brachydactyly type E, severe salt-independent but age-dependent hypertension, an increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, and altered baroreflex blood pressure regulation. It results in death from stroke before age 50 years when untreated. Brachydactyly type E is characterized by shortening of the fingers mainly in the metacarpals and metatarsals. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by cGMP. Inhibited by 17beta-estradiol. Inhibited by milrinone.

Cofactor. Binds 2 divalent metal cations per subunit. Binds 2 divalent metal cations per subunit.

Similarity. Belongs to the cyclic nucleotide phosphodiesterase family. PDE3 subfamily.

RefSeq proteins (5): NP_000912, NP_001231612, NP_001365336, NP_001365337, NP_001365338 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002073	PDEase_catalytic_dom	Domain
IPR003607	HD/PDEase_dom	Domain
IPR023174	PDEase_CS	Conserved_site
IPR036971	PDEase_catalytic_dom_sf	Homologous_superfamily

Pfam: PF00233

Enzyme classification (BRENDA):

• EC 3.1.4.17 — 3’,5’-cyclic-nucleotide phosphodiesterase (BRENDA: 27 organisms, 83 substrates, 296 inhibitors, 106 Km, 31 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
3’,5’-CAMP	0.0001–7	41
3’,5’-CGMP	—	23
CAMP	0.0002–1.6	15
CGMP	0.0002–1	12
2’,3’-CAMP	0.0038–0.0052	2
5’-AMP	0.0014–0.0016	2
5’-ATP	0.0033–0.0125	2
5’-PAPA	0.204	1
5’-PAPG	0.355	1
ADENOSINE 3’,5’-CYCLIC PHOSPHATE	0.012	1
GUANOSINE 3’,5’-CYCLIC PHOSPHATE	0.025	1

Catalyzed reactions (Rhea), 4 shown:

• a nucleoside 3’,5’-cyclic phosphate + H2O = a nucleoside 5’-phosphate + H(+) (RHEA:14653)
• 3’,5’-cyclic GMP + H2O = GMP + H(+) (RHEA:16957)
• 3’,5’-cyclic AMP + H2O = AMP + H(+) (RHEA:25277)
• 3’,5’-cyclic UMP + H2O = UMP + H(+) (RHEA:70575)

UniProt features (87 total): helix 23, binding site 9, strand 9, modified residue 8, sequence variant 7, transmembrane region 6, region of interest 6, compositionally biased region 6, turn 4, sequence conflict 3, mutagenesis site 2, chain 1, active site 1, cross-link 1, domain 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
7L27	X-RAY DIFFRACTION	1.7
7KWE	X-RAY DIFFRACTION	2
7L29	X-RAY DIFFRACTION	2.08
7L28	X-RAY DIFFRACTION	2.2
7LRC	ELECTRON MICROSCOPY	2.97
7EG1	ELECTRON MICROSCOPY	3.2
7EG4	ELECTRON MICROSCOPY	3.2
7LRD	ELECTRON MICROSCOPY	3.22
7EG0	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14432-F1	61.11	0.30

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): 752 (proton donor)

Ligand- & substrate-binding residues (9): 752; 756; 836; 837; 837; 837; 950; 950; 1001

Post-translational modifications (9): 312, 428, 438, 492, 520, 524, 1033, 1036, 1120

Mutagenesis-validated functional residues (2):

Position	Phenotype
867	loss of interaction with slfn12.
914	loss of interaction with slfn12.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 277 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_OOGENESIS, AP4_Q6, CERVERA_SDHB_TARGETS_1_DN, CACCAGC_MIR138, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CAGCTG_AP4_Q5, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (19): oocyte maturation (GO:0001556), lipid metabolic process (GO:0006629), G protein-coupled receptor signaling pathway (GO:0007186), response to xenobiotic stimulus (GO:0009410), regulation of meiotic nuclear division (GO:0040020), negative regulation of apoptotic process (GO:0043066), negative regulation of vascular permeability (GO:0043116), positive regulation of vascular permeability (GO:0043117), positive regulation of oocyte development (GO:0060282), regulation of ribonuclease activity (GO:0060700), cellular response to cGMP (GO:0071321), cellular response to transforming growth factor beta stimulus (GO:0071560), apoptotic signaling pathway (GO:0097190), negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0106072), negative regulation of cAMP/PKA signal transduction (GO:0141162), signal transduction (GO:0007165), obsolete cGMP-mediated signaling (GO:0019934), nuclear receptor-mediated steroid hormone signaling pathway (GO:0030518), oocyte development (GO:0048599)

GO Molecular Function (10): 3’,5’-cyclic-nucleotide phosphodiesterase activity (GO:0004114), 3’,5’-cyclic-AMP phosphodiesterase activity (GO:0004115), 3’,5’-cGMP-inhibited cyclic-nucleotide phosphodiesterase activity (GO:0004119), nuclear estrogen receptor activity (GO:0030284), metal ion binding (GO:0046872), 3’,5’-cyclic-GMP phosphodiesterase activity (GO:0047555), estrogen binding (GO:0099130), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (3): cytosol (GO:0005829), membrane (GO:0016020), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
3’,5’-cyclic-nucleotide phosphodiesterase activity	3
cellular anatomical structure	3
oocyte development	2
signal transduction	2
apoptotic process	2
regulation of vascular permeability	2
developmental process involved in reproduction	1
cell maturation	1
primary metabolic process	1
G protein-coupled receptor activity	1
response to chemical	1
regulation of cell cycle process	1
regulation of meiotic cell cycle	1
regulation of nuclear division	1
meiotic nuclear division	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
positive regulation of cell development	1
regulation of oocyte development	1
positive regulation of reproductive process	1
RNA nuclease activity	1
regulation of catalytic activity	1
regulation of RNA metabolic process	1
response to cGMP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
cellular response to growth factor stimulus	1
response to transforming growth factor beta	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
negative regulation of G protein-coupled receptor signaling pathway	1
regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
cAMP/PKA signal transduction	1
regulation of cAMP/PKA signal transduction	1
negative regulation of intracellular signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
steroid hormone receptor signaling pathway	1

Protein interactions and networks

STRING

982 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE3A	ALDH7A1	P49419	899
PDE3A	SLFN12	Q8IYM2	745
PDE3A	AKAP7	O43687	726
PDE3A	PRKACA	P17612	704
PDE3A	PRKACB	P22694	688
PDE3A	PRKACG	P22612	686
PDE3A	GPR3	P46089	593
PDE3A	PLEC	Q15149	582
PDE3A	NPPC	P23582	571
PDE3A	PDE4A	P27815	559
PDE3A	PIK3CG	P48736	548
PDE3A	NPR2	P20594	545
PDE3A	SLCO1C1	Q9NYB5	545
PDE3A	PDE11A	Q9HCR9	534
PDE3A	CFTR	P13569	515

IntAct

30 interactions, top by confidence:

A	B	Type	Score
ARFGEF1	PDE3A	psi-mi:“MI:0914”(association)	0.580
ARFGEF1	PDE3A	psi-mi:“MI:0915”(physical association)	0.580
PDE3A	ARFGEF2	psi-mi:“MI:0915”(physical association)	0.500
ARFGEF1	PRKAR1A	psi-mi:“MI:0914”(association)	0.500
ARFGEF2	PDE3A	psi-mi:“MI:0914”(association)	0.500
PDE3A	ARFGEF2	psi-mi:“MI:0914”(association)	0.500
ARFGEF1	PRKAR1A	psi-mi:“MI:0915”(physical association)	0.500
PDE3A	YWHAZ	psi-mi:“MI:0915”(physical association)	0.400
Cenpe	BBX	psi-mi:“MI:0914”(association)	0.350
Spred2	TARS3	psi-mi:“MI:0914”(association)	0.350
Kctd5		psi-mi:“MI:0914”(association)	0.350
Ccser2	PAFAH1B1	psi-mi:“MI:0914”(association)	0.350
Cep44	SSR3	psi-mi:“MI:0914”(association)	0.350
Cenph	CENPX	psi-mi:“MI:0914”(association)	0.350
Pcdh1	SRI	psi-mi:“MI:0914”(association)	0.350
WDR62	MAPKBP1	psi-mi:“MI:0914”(association)	0.350
TUBA1C	TCP11L2	psi-mi:“MI:0914”(association)	0.350
KIF11	MAP4	psi-mi:“MI:0914”(association)	0.350
CCDC88A		psi-mi:“MI:0914”(association)	0.350
HSPA5	NCOR2	psi-mi:“MI:0914”(association)	0.350
FBXO7	ZBTB48	psi-mi:“MI:0914”(association)	0.350
PDE3A	PRKAR1A	psi-mi:“MI:0914”(association)	0.350
ARFGEF2	PRKAR1A	psi-mi:“MI:0914”(association)	0.350
PA	DDX39A	psi-mi:“MI:0914”(association)	0.350
PDE3A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
PDE3A	SUN1	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
PDE3A	BMH1	psi-mi:“MI:0914”(association)	0.350

BioGRID (87): PDE3A (Biochemical Activity), PDE3A (Biochemical Activity), PDE3A (Affinity Capture-MS), PDE3A (Affinity Capture-MS), PDE3A (Affinity Capture-MS), PDE3A (Affinity Capture-MS), PDE3A (Affinity Capture-MS), PDE3A (Affinity Capture-MS), PDE3A (Affinity Capture-MS), PDE3A (Affinity Capture-MS), PDE3A (Affinity Capture-MS), PDE3A (Affinity Capture-MS), PDE3A (Affinity Capture-MS), PDE3A (Affinity Capture-MS), PDE3A (Affinity Capture-MS)

ESM2 similar proteins: A0JPH4, A3KFU9, A6H7H1, A7UA95, B9U3F2, D3ZWZ9, D4A6L0, E1BBQ2, F1M8G0, O15040, O54828, O75129, O88974, P49805, P97260, Q00M95, Q12770, Q13370, Q14432, Q15047, Q3B7M3, Q3B7T1, Q4ZIN3, Q5MNU5, Q5R9R1, Q5T848, Q5VW38, Q5ZKN3, Q61409, Q62865, Q63085, Q6A0A9, Q6F6B3, Q6GQV7, Q6L8S8, Q6P6V6, Q6PJF5, Q80WQ6, Q80Z10, Q86XL3

Diamond homologs: A0A077YBL0, B0G0Y8, B3LVW5, B3P3K2, B4JXX2, B4K9L4, B4LVU6, B4NAL6, B4PSS5, B4QZU1, B7YZV4, E9Q4S1, H2QL32, O00408, O08593, O18696, O60658, O70628, O76083, O88502, O89084, O95263, P0C1Q2, P12252, P14099, P14100, P14270, P14644, P14646, P16586, P23439, P23440, P27815, P30645, P33726, P35913, P51160, P54748, P54750, P70453

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
PRKACA	unknown	PDE3A	phosphorylation
PRKCA	up-regulates	PDE3A	phosphorylation
PDE3A	“down-regulates activity”	ATP2A2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Hemostasis	6	13.5×	7e-04
Cell Cycle	5	11.3×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	2
Uncertain significance	190
Likely benign	50
Benign	67

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
193020	NM_000921.5(PDE3A):c.1334C>A (p.Thr445Asn)	Pathogenic
193021	NM_000921.5(PDE3A):c.1333A>G (p.Thr445Ala)	Pathogenic
193022	NM_000921.5(PDE3A):c.1334C>G (p.Thr445Ser)	Pathogenic
193023	NM_000921.5(PDE3A):c.1339G>A (p.Ala447Thr)	Pathogenic
193024	NM_000921.5(PDE3A):c.1340C>T (p.Ala447Val)	Pathogenic
193025	NM_000921.5(PDE3A):c.1346G>T (p.Gly449Val)	Pathogenic
977321	NM_000921.5(PDE3A):c.1346G>A (p.Gly449Asp)	Pathogenic
1298541	NM_000921.5(PDE3A):c.2551A>G (p.Thr851Ala)	Likely pathogenic
690366	NM_000921.5(PDE3A):c.1324ACC[3] (p.Thr445del)	Likely pathogenic

SpliceAI

4816 predictions. Top by Δscore:

Variant	Effect	Δscore
12:20384205:A:AG	acceptor_gain	1.0000
12:20425758:A:G	acceptor_gain	1.0000
12:20456154:A:T	donor_gain	1.0000
12:20556656:CCA:C	acceptor_loss	1.0000
12:20556657:CAG:C	acceptor_loss	1.0000
12:20556658:A:AC	acceptor_loss	1.0000
12:20556658:A:AG	acceptor_gain	1.0000
12:20556659:G:GG	acceptor_gain	1.0000
12:20556659:GC:G	acceptor_gain	1.0000
12:20556659:GCT:G	acceptor_gain	1.0000
12:20556659:GCTC:G	acceptor_gain	1.0000
12:20556659:GCTCA:G	acceptor_gain	1.0000
12:20556708:CAG:C	donor_gain	1.0000
12:20556708:CAGGT:C	donor_loss	1.0000
12:20556709:AG:A	donor_gain	1.0000
12:20556709:AGG:A	donor_loss	1.0000
12:20556710:GG:G	donor_gain	1.0000
12:20556711:G:GG	donor_gain	1.0000
12:20556711:GTA:G	donor_loss	1.0000
12:20613441:A:AG	acceptor_gain	1.0000
12:20613442:G:GT	acceptor_gain	1.0000
12:20613699:AGG:A	donor_loss	1.0000
12:20613701:G:GA	donor_loss	1.0000
12:20616368:G:GT	donor_gain	1.0000
12:20621271:A:AG	acceptor_gain	1.0000
12:20621272:A:G	acceptor_gain	1.0000
12:20621284:T:A	acceptor_gain	1.0000
12:20621285:G:A	acceptor_gain	1.0000
12:20621294:A:AG	acceptor_gain	1.0000
12:20621295:G:GC	acceptor_gain	1.0000

AlphaMissense

7452 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:20637172:T:A	W692R	1.000
12:20637172:T:C	W692R	1.000
12:20646492:C:G	H752D	1.000
12:20646504:C:G	H756D	1.000
12:20646508:C:A	A757D	1.000
12:20646894:G:C	D837H	1.000
12:20646895:A:C	D837A	1.000
12:20646895:A:G	D837G	1.000
12:20646895:A:T	D837V	1.000
12:20646896:T:A	D837E	1.000
12:20646896:T:G	D837E	1.000
12:20646903:C:G	H840D	1.000
12:20646904:A:G	H840R	1.000
12:20646905:T:A	H840Q	1.000
12:20646905:T:G	H840Q	1.000
12:20646910:G:A	G842E	1.000
12:20646920:T:A	N845K	1.000
12:20646920:T:G	N845K	1.000
12:20646924:T:C	F847L	1.000
12:20646925:T:C	F847S	1.000
12:20646926:C:A	F847L	1.000
12:20646926:C:G	F847L	1.000
12:20646928:T:C	L848P	1.000
12:20648702:C:A	N860K	1.000
12:20648702:C:G	N860K	1.000
12:20648704:A:T	D861V	1.000
12:20648713:T:A	V864D	1.000
12:20648719:A:T	E866V	1.000
12:20648723:T:A	N867K	1.000
12:20648723:T:G	N867K	1.000

dbSNP variants (sampled 300 via entrez): RS1000006800 (12:20547384 C>A), RS1000021085 (12:20398610 C>T), RS1000032721 (12:20573210 T>C,G), RS1000033511 (12:20614688 G>A,C), RS1000041314 (12:20630600 A>G), RS1000043238 (12:20579674 T>C), RS1000053053 (12:20379207 G>A), RS1000067398 (12:20488750 C>T), RS1000073225 (12:20417914 A>C), RS1000083475 (12:20524909 T>C,G), RS1000091710 (12:20414797 G>A,C), RS1000102215 (12:20501649 GT>G), RS1000118793 (12:20467371 G>A), RS1000123541 (12:20454536 G>A), RS1000123945 (12:20544732 A>C,G)

Disease associations

OMIM: gene MIM:123805 | disease phenotypes: MIM:112410

GenCC curated gene-disease

Disease	Classification	Inheritance
brachydactyly-arterial hypertension syndrome	Strong	Autosomal dominant

Mondo (3): brachydactyly-arterial hypertension syndrome (MONDO:0007211), prostate cancer (MONDO:0008315), intellectual disability (MONDO:0001071)

Orphanet (3): Brachydactyly-arterial hypertension syndrome (Orphanet:1276), Familial prostate cancer (Orphanet:1331), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000822	Hypertension
HP:0001156	Brachydactyly
HP:0004322	Short stature
HP:0005863	Type E brachydactyly
HP:0009803	Short phalanx of finger
HP:0010049	Short metacarpal
HP:0010579	Cone-shaped epiphysis

GWAS associations

68 associations (top):

Study	Trait	p-value
GCST000175_11	Height	2.000000e-06
GCST000412_3	Male infertility	5.000000e-07
GCST000442_6	Aortic root size	2.000000e-08
GCST000452_12	QT interval	1.000000e-06
GCST000755_9	HDL cholesterol	4.000000e-08
GCST001204_3	Response to platinum-based chemotherapy (carboplatin)	8.000000e-07
GCST001465_17	Adiponectin levels	4.000000e-08
GCST001510_7	Response to TNF-alpha inhibitors in rheumatoid arthritis	2.000000e-06
GCST002223_67	HDL cholesterol	1.000000e-08
GCST002307_3	Systolic blood pressure (alcohol consumption interaction)	6.000000e-07
GCST003273_18	Diastolic blood pressure	2.000000e-16
GCST003818_4	Resting heart rate	3.000000e-09
GCST004232_69	HDL cholesterol levels	5.000000e-09
GCST004278_66	Pulse pressure	7.000000e-15
GCST004279_27	Systolic blood pressure	5.000000e-09
GCST004280_52	Diastolic blood pressure	2.000000e-06
GCST004280_71	Diastolic blood pressure	5.000000e-22
GCST004744_63	Lung adenocarcinoma	3.000000e-06
GCST004776_46	Systolic blood pressure	1.000000e-14
GCST004776_62	Systolic blood pressure	2.000000e-08
GCST004776_96	Systolic blood pressure	2.000000e-08
GCST004777_28	Diastolic blood pressure	5.000000e-09
GCST004777_29	Diastolic blood pressure	2.000000e-07
GCST005173_38	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	2.000000e-06
GCST005789_19	Resting heart rate	2.000000e-07
GCST005908_39	Height	3.000000e-08
GCST006187_36	Diastolic blood pressure (cigarette smoking interaction)	1.000000e-35
GCST006188_38	Systolic blood pressure (cigarette smoking interaction)	2.000000e-11
GCST006258_22	Diastolic blood pressure	2.000000e-15
GCST006259_7	Systolic blood pressure	4.000000e-07

EFO canonical traits (22, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004502	adiponectin measurement
EFO:0004653	response to TNF antagonist
EFO:0004329	alcohol drinking
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004723	coronary artery calcification
EFO:0006527	smoking status measurement
EFO:0004847	age at onset
EFO:0009959	diverticular disease
EFO:0006340	mean arterial pressure
EFO:0004530	triglyceride measurement
EFO:0007636	attention function measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004462	PR interval
EFO:0004340	body mass index
EFO:0004980	appendicular lean mass
EFO:0007874	gut microbiome measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C537095	Brachydactyly with hypertension (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2094125 (PROTEIN FAMILY), CHEMBL2095153 (SELECTIVITY GROUP), CHEMBL2111400 (SELECTIVITY GROUP), CHEMBL2363066 (PROTEIN FAMILY), CHEMBL241 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

162 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 752,189 (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
CHEMBL12856	INAMRINONE	4	9,690
CHEMBL1520	VARDENAFIL	4	21,078
CHEMBL189	MILRINONE	4	20,605
CHEMBL191	LOSARTAN	4	88,932
CHEMBL192	SILDENAFIL	4	41,819
CHEMBL249856	ENOXIMONE	4	5,206
CHEMBL484785	CRISABOROLE	4	1,482
CHEMBL760	ANAGRELIDE	4	23,754
CHEMBL799	CILOSTAZOL	4	20,017
CHEMBL932	DIPYRIDAMOLE	4	51,743
CHEMBL995	LOSARTAN POTASSIUM	4	11,860
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1017	TELMISARTAN	4	27,457
CHEMBL1024	IFOSFAMIDE	4	139,212
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL1096	AMLEXANOX	4	4,195
CHEMBL111	RIMONABANT	4	15,726
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1165	MOEXIPRIL	4	14,871
CHEMBL119	TRIMETREXATE	4	57,002
CHEMBL1200438	TIOCONAZOLE	4
CHEMBL1200692	OLMESARTAN MEDOXOMIL	4
CHEMBL1200848	HYDROXYPROGESTERONE CAPROATE	4
CHEMBL1200973	ESTRADIOL CYPIONATE	4
CHEMBL1201	THIOTHIXENE	4
CHEMBL1201304	INDOCYANINE GREEN ACID FORM	4
CHEMBL1201314	VALGANCICLOVIR	4
CHEMBL1221	SULCONAZOLE	4
CHEMBL1242	PHENAZOPYRIDINE	4
CHEMBL1289494	TIVOZANIB	4

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12305038	Toxicity	3	opioids	Nausea;Vomiting
rs12579720	Efficacy	3	hydrochlorothiazide	Hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12305038	PDE3A	3	0.00	1	opioids

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphodiesterases, 3’,5’-cyclic nucleotide (PDEs)

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
ensifentrine	Inhibition	9.4	pIC50
cilostamide	Inhibition	7.5	pIC50
anagrelide	Inhibition	7.27	pIC50
cilostazol	Inhibition	6.7	pIC50
milrinone	Inhibition	6.36	pIC50
papaverine	Inhibition	6.04	pIC50
enoximone	Inhibition	5.42	pIC50
inamrinone	Inhibition	4.8	pIC50
ibudilast	Inhibition	3.52	pIC50

Binding affinities (BindingDB)

128 measured of 148 human assays (179 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(5R)-5-methyl-6-{4-[(3-oxo-2-{[3-(thiophen-3-yl)phenyl]methyl}cyclohex-1-en-1-yl)amino]phenyl}-2,3,4,5-tetrahydropyridazin-3-one	IC50	0.11 nM
(5R)-5-methyl-6-{4-[(2-{[3-(3-nitrophenyl)phenyl]methyl}-3-oxocyclohex-1-en-1-yl)amino]phenyl}-2,3,4,5-tetrahydropyridazin-3-one	IC50	0.11 nM
dihydropyridazinone 14e	IC50	0.33 nM
(5R)-6-[4-({2-[(2-methoxyphenyl)methyl]-3-oxocyclohex-1-en-1-yl}amino)phenyl]-5-methyl-2,3,4,5-tetrahydropyridazin-3-one	IC50	0.39 nM
(5R)-5-methyl-6-{4-[(3-oxo-2-{[2-(trifluoromethyl)phenyl]methyl}cyclohex-1-en-1-yl)amino]phenyl}-2,3,4,5-tetrahydropyridazin-3-one	IC50	0.83 nM
(5R)-6-[4-({2-[(3-bromophenyl)methyl]-3-oxocyclohex-1-en-1-yl}amino)phenyl]-5-methyl-2,3,4,5-tetrahydropyridazin-3-one	IC50	0.94 nM
6-[[8-fluoro-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-N-(1-methylpiperidin-4-yl)quinolin-3-amine	IC50	1 nM	US-9062045: Triazolopyridine compounds
(3S)-1-[6-[[8-fluoro-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl]-N,N-dimethylpyrrolidin-3-amine	IC50	1 nM	US-9062045: Triazolopyridine compounds
2-[[6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl]amino]ethanol	IC50	1 nM	US-9062045: Triazolopyridine compounds
6-{4-[(2-benzyl-3-oxocyclohex-1-en-1-yl)amino]-3-fluorophenyl}-5-methyl-2,3,4,5-tetrahydropyridazin-3-one	IC50	1.2 nM
(5R)-6-{4-[(2-benzyl-3-oxocyclohex-1-en-1-yl)amino]phenyl}-5-methyl-2,3,4,5-tetrahydropyridazin-3-one	IC50	1.3 nM
6-[[8-fluoro-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-amine	IC50	1.3 nM	US-9062045: Triazolopyridine compounds
6-{4-[(2-benzyl-3-oxocyclohex-1-en-1-yl)amino]-2-fluorophenyl}-5-methyl-2,3,4,5-tetrahydropyridazin-3-one	IC50	1.6 nM
6-{4-[(2-benzyl-3-oxocyclohex-1-en-1-yl)amino]-2,5-difluorophenyl}-5-methyl-2,3,4,5-tetrahydropyridazin-3-one	IC50	1.6 nM
(3S)-N,N-dimethyl-1-[6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl]pyrrolidin-3-amine	IC50	2 nM	US-9062045: Triazolopyridine compounds
1-[6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl]piperidin-4-amine	IC50	2 nM	US-9062045: Triazolopyridine compounds
6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-3-(4-piperidin-1-ylpiperidin-1-yl)quinoline	IC50	2 nM	US-9062045: Triazolopyridine compounds
3-(4-methoxypiperidin-1-yl)-6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinoline	IC50	2 nM	US-9062045: Triazolopyridine compounds
4-[6-[(6-pyrazolidin-4-yl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)sulfanyl]quinolin-3-yl]morpholine	IC50	2 nM	US-9062045: Triazolopyridine compounds
2-[(E)-1-[3-(3-morpholin-4-ylquinolin-6-yl)sulfanyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl]ethylideneamino]oxyethanol	IC50	2 nM	US-9062045: Triazolopyridine compounds
(5S)-6-[4-(3-hydroxy-3-methylazetidin-1-yl)-3-(trifluoromethyl)phenyl]-5-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one	IC50	2 nM	US-20250170136: 1,2,4-TRIAZIN-3(2H)-ONE COMPOUNDS FOR THE TREATMENT OF HYPERPROLIFERATIVE DISEASES
(5S)-6-[4-(cyclopentylamino)-3-(trifluoromethyl)phenyl]-5-methyl-4,5-dihydro-1,2,4-triazin-3(2H)-one	IC50	2 nM	US-20250170136: 1,2,4-TRIAZIN-3(2H)-ONE COMPOUNDS FOR THE TREATMENT OF HYPERPROLIFERATIVE DISEASES
3-[4-({2-[(2,6-dichlorophenyl)methyl]-3-oxocyclohex-1-en-1-yl}amino)-2-fluorophenyl]-4,4-dimethyl-4,5-dihydro-1H-pyrazol-5-one	IC50	2.2 nM
(5R)-6-[4-({2-[(4-methoxyphenyl)methyl]-3-oxocyclohex-1-en-1-yl}amino)phenyl]-5-methyl-2,3,4,5-tetrahydropyridazin-3-one	IC50	2.3 nM
(5R)-6-[4-({2-[(3-fluorophenyl)methyl]-3-oxocyclohex-1-en-1-yl}amino)phenyl]-5-methyl-2,3,4,5-tetrahydropyridazin-3-one	IC50	2.8 nM
benzyl N-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl]carbamate	IC50	2.9 nM
1-[6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl]piperidin-3-amine	IC50	3 nM	US-9062045: Triazolopyridine compounds
6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-3-piperazin-1-ylquinoline	IC50	3 nM	US-9062045: Triazolopyridine compounds
6-[[8-fluoro-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-3-(4-piperidin-1-ylpiperidin-1-yl)quinoline	IC50	3 nM	US-9062045: Triazolopyridine compounds
4-[6-[(8-fluoro-6-pyrazolidin-4-yl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)sulfanyl]quinolin-3-yl]morpholine	IC50	3 nM	US-9062045: Triazolopyridine compounds
3-methyl-4-[6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl]morpholine	IC50	3 nM	US-9062045: Triazolopyridine compounds
4-[6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl]morpholine	IC50	3 nM	US-9062045: Triazolopyridine compounds
4-[6-[[8-fluoro-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl]morpholine	IC50	3 nM	US-9062045: Triazolopyridine compounds
6-[difluoro-[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl]quinoline	IC50	3 nM	US-9062045: Triazolopyridine compounds
6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinoline	IC50	3 nM	US-9062045: Triazolopyridine compounds
6-[[8-fluoro-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-3-(1-methylpyrazol-4-yl)quinoline	IC50	3 nM	US-9062045: Triazolopyridine compounds
(5R)-5-methyl-6-[4-({2-[(3-nitrophenyl)methyl]-3-oxocyclohex-1-en-1-yl}amino)phenyl]-2,3,4,5-tetrahydropyridazin-3-one	IC50	3.1 nM
6-{4-[(2-benzyl-3-oxocyclohex-1-en-1-yl)amino]-3-methylphenyl}-5-methyl-2,3,4,5-tetrahydropyridazin-3-one	IC50	3.7 nM
N-(1-methylpiperidin-4-yl)-6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-amine	IC50	4 nM	US-9062045: Triazolopyridine compounds
3-[(3S,5R)-3,5-dimethylpiperazin-1-yl]-6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinoline	IC50	4 nM	US-9062045: Triazolopyridine compounds
1-[6-[[8-fluoro-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl]piperidin-4-ol	IC50	4 nM	US-9062045: Triazolopyridine compounds
6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-N-(oxolan-3-yl)quinolin-3-amine	IC50	4 nM	US-9062045: Triazolopyridine compounds
3-(4,4-difluoropiperidin-1-yl)-6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinoline	IC50	4 nM	US-9062045: Triazolopyridine compounds
3-(4-methylpiperazin-1-yl)-6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinoline	IC50	4 nM	US-9062045: Triazolopyridine compounds
ethyl (9R)-9-[5-(1H-benzimidazol-2-ylsulfanyl)furan-2-yl]-8-oxo-2,4,5,6,7,9-hexahydropyrrolo[3,4-b]quinoline-3-carboxylate	IC50	4 nM	US-9073917: Anti-cancer compound and pharmaceutical composition containing the same
2-[4-[3-(quinolin-6-ylmethyl)triazolo[4,5-b]pyrazin-5-yl]pyrazol-1-yl]ethanol	IC50	4 nM	US-9062045: Triazolopyridine compounds
(5S)-5-methyl-6-[4-{[(2R)-3,3,3-trifluoro-2-hydroxypropyl]amino}-3-(trifluoromethyl)phenyl]-4,5-dihydro-1,2,4-triazin-3(2H)-one	IC50	4 nM	US-20250170136: 1,2,4-TRIAZIN-3(2H)-ONE COMPOUNDS FOR THE TREATMENT OF HYPERPROLIFERATIVE DISEASES
(5S)-5-methyl-6-[4-{[(pyrazin-2-yl)methyl]amino}-3-(trifluoromethyl)phenyl]-4,5-dihydro-1,2,4-triazin-3(2H)-one	IC50	4 nM	US-20250170136: 1,2,4-TRIAZIN-3(2H)-ONE COMPOUNDS FOR THE TREATMENT OF HYPERPROLIFERATIVE DISEASES
6-[(4-bromophenyl)methyl]-1,3-dimethyl-5,6,8,8a-tetrahydro-4aH-pyrido[2,3-d]pyrimidine-2,4,7-trione	IC50	4.8 nM	US-9242982: Pyridopyrimidine based derivatives as potential phosphodiesterase 3 (PDE3) inhibitors and a process for the preparation thereof
(2S)-2-methyl-4-[6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl]morpholine	IC50	5 nM	US-9062045: Triazolopyridine compounds

ChEMBL bioactivities

1455 potent at pChembl≥5 of 1894 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	IC50	0.03	nM	CHEMBL327234
10.10	IC50	0.08	nM	CHEMBL88787
10.00	IC50	0.1	nM	CHEMBL5081214
9.96	IC50	0.11	nM	CHEMBL338860
9.96	IC50	0.11	nM	CHEMBL339210
9.90	IC50	0.1259	nM	CHEMBL5080391
9.80	IC50	0.1585	nM	CHEMBL5087564
9.70	IC50	0.2	nM	CHEMBL90877
9.70	IC50	0.2	nM	CHEMBL329173
9.60	IC50	0.2512	nM	CHEMBL5094110
9.57	IC50	0.27	nM	CHEMBL2337969
9.52	IC50	0.3	nM	CHEMBL88108
9.52	IC50	0.3	nM	CHEMBL91503
9.52	IC50	0.3	nM	CHEMBL328543
9.52	IC50	0.3	nM	CHEMBL90647
9.50	IC50	0.3162	nM	CHEMBL5086895
9.50	IC50	0.3162	nM	CHEMBL5076558
9.48	IC50	0.33	nM	CHEMBL131355
9.41	IC50	0.39	nM	CHEMBL131111
9.40	IC50	0.4	nM	CHEMBL431799
9.40	IC50	0.4	nM	CHEMBL432057
9.40	IC50	0.4	nM	CHEMBL329788
9.40	IC50	0.4	nM	CHEMBL91388
9.40	IC50	0.4	nM	ORISMILAST
9.30	IC50	0.5	nM	CHEMBL90804
9.30	IC50	0.5	nM	CHEMBL92165
9.22	IC50	0.6	nM	CHEMBL91715
9.22	IC50	0.6	nM	CHEMBL91088
9.20	IC50	0.63	nM	CHEMBL1203032
9.15	IC50	0.7	nM	CHEMBL90876
9.15	IC50	0.7	nM	CHEMBL329573
9.15	IC50	0.7	nM	CHEMBL330086
9.15	IC50	0.7	nM	CHEMBL433183
9.15	IC50	0.7	nM	CHEMBL431085
9.12	IC50	0.76	nM	CHEMBL5625125
9.09	IC50	0.81	nM	CHEMBL1203039
9.09	IC50	0.81	nM	CHEMBL1203053
9.08	IC50	0.84	nM	CHEMBL1203031
9.08	IC50	0.83	nM	CHEMBL338381
9.05	IC50	0.9	nM	CHEMBL91014
9.05	IC50	0.9	nM	CHEMBL91249
9.05	IC50	0.9	nM	ANAGRELIDE
9.03	IC50	0.94	nM	CHEMBL326891
9.03	IC50	0.94	nM	CHEMBL128621
9.00	IC50	1	nM	CHEMBL92264
9.00	IC50	1	nM	CHEMBL88245
9.00	IC50	1	nM	CHEMBL313021
9.00	IC50	1	nM	CHEMBL90176
9.00	IC50	1	nM	CHEMBL5078680
9.00	IC50	1	nM	CHEMBL5088742

PubChem BioAssay actives

1063 with measured affinity, of 5036 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
7-[5-[4-(cyclohexylmethyl)piperazin-1-yl]-5-oxopentoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	<0.0001	uM
7-[5-(4-benzylpiperazin-1-yl)-5-oxopentoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0001	uM
(4R)-4-methyl-3-[4-[[3-oxo-2-[(3-thiophen-3-ylphenyl)methyl]cyclohexen-1-yl]amino]phenyl]-4,5-dihydro-1H-pyridazin-6-one	1797368: PDE SPA Enzyme Inhibition Assay from Article 10.1016/j.bmcl.2003.08.056: “Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors.”	ic50	0.0001	uM
(4R)-4-methyl-3-[4-[[2-[[3-(3-nitrophenyl)phenyl]methyl]-3-oxocyclohexen-1-yl]amino]phenyl]-4,5-dihydro-1H-pyridazin-6-one	1797368: PDE SPA Enzyme Inhibition Assay from Article 10.1016/j.bmcl.2003.08.056: “Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors.”	ic50	0.0001	uM
(4R)-4-methyl-3-[4-[[3-oxo-2-[(2-thiophen-3-ylphenyl)methyl]cyclohexen-1-yl]amino]phenyl]-4,5-dihydro-1H-pyridazin-6-one	159499: Inhibitory concentration required to inhibit human phosphodiesterase 3A expressed in Escherichia coli	ic50	0.0001	uM
(4R)-4-methyl-3-[4-[[2-[[2-(3-nitrophenyl)phenyl]methyl]-3-oxocyclohexen-1-yl]amino]phenyl]-4,5-dihydro-1H-pyridazin-6-one	159499: Inhibitory concentration required to inhibit human phosphodiesterase 3A expressed in Escherichia coli	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]sulfamoyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-[[N-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxycarbonyl]anilino]methyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0001	uM
7-[4-[4-(cycloheptylmethyl)piperazin-1-yl]-4-oxobutoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0002	uM
7-[4-[4-(2-cyclohexylethyl)piperazin-1-yl]-4-oxobutoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0002	uM
[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]amino]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0002	uM
2-[cyclohexyl-[4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanoyl]amino]acetic acid	158576: Inhibition of human platelet PDE by inhibiting cyclic Adenosine monophosphate (cAMP) hydrolysis	ic50	0.0003	uM
tert-butyl 4-[4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanoyl]piperazine-1-carboxylate	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0003	uM
7-[4-oxo-4-[4-[2-[2-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]butoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0003	uM
7-[4-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-4-oxobutoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0003	uM
3-[4-[[2-[(3-iodophenyl)methyl]-3-oxocyclohexen-1-yl]amino]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one	159499: Inhibitory concentration required to inhibit human phosphodiesterase 3A expressed in Escherichia coli	ic50	0.0003	uM
(4R)-3-[4-[[2-[(3-iodophenyl)methyl]-3-oxocyclohexen-1-yl]amino]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one	1797368: PDE SPA Enzyme Inhibition Assay from Article 10.1016/j.bmcl.2003.08.056: “Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors.”	ic50	0.0003	uM
9,10-dimethoxy-3-methyl-2-(2,4,6-trimethylphenyl)imino-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one	1799753: Enzymatic Assay from Article 10.1074/jbc.M111.326777: “Biological and structural characterization of Trypanosoma cruzi phosphodiesterase C and Implications for design of parasite selective inhibitors.”	ic50	0.0003	uM
6-(2-ethyl-7-methoxypyrazolo[1,5-a]pyridin-4-yl)-2-[4-[4-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)phenoxy]butyl]-4,5-dihydropyridazin-3-one	732945: Inhibition of PDE3A (unknown origin) by radiochemical assay	ic50	0.0003	uM
[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]amino]methyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0003	uM
[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]sulfamoyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0003	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-[[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]amino]methyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0003	uM
N-cycloheptyl-N-methyl-5-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]pentanamide	158576: Inhibition of human platelet PDE by inhibiting cyclic Adenosine monophosphate (cAMP) hydrolysis	ic50	0.0004	uM
7-[4-oxo-4-[4-(2-propylpentyl)piperazin-1-yl]butoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0004	uM
7-[4-oxo-4-[4-[[4-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]butoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0004	uM
(4R)-3-[4-[[2-[(2-methoxyphenyl)methyl]-3-oxocyclohexen-1-yl]amino]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one	1797368: PDE SPA Enzyme Inhibition Assay from Article 10.1016/j.bmcl.2003.08.056: “Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors.”	ic50	0.0004	uM
3-[4-[[2-[(2-methoxyphenyl)methyl]-3-oxocyclohexen-1-yl]amino]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one	159499: Inhibitory concentration required to inhibit human phosphodiesterase 3A expressed in Escherichia coli	ic50	0.0004	uM
2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-[7-(difluoromethoxy)-1’,1’-dioxospiro[1,3-benzodioxole-2,4’-thiane]-4-yl]ethanone	2033924: Inhibition of PDE3 (unknown origin)	ic50	0.0004	uM
7-[4-[4-(cyclohexylmethyl)piperazin-1-yl]-4-oxobutoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0004	uM
methyl 2-[cyclohexyl-[4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanoyl]amino]acetate	158576: Inhibition of human platelet PDE by inhibiting cyclic Adenosine monophosphate (cAMP) hydrolysis	ic50	0.0005	uM
7-[4-[4-(cyclopentylmethyl)piperazin-1-yl]-4-oxobutoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0005	uM
7-[6-[4-(cyclohexylmethyl)piperazin-1-yl]-6-oxohexoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0006	uM
7-[4-oxo-4-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]butoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0006	uM
7-[3-(1-benzylpiperidin-4-yl)sulfonylpropoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one;hydrochloride	158575: Inhibition of human platelet aggregation cAMP PDE in vitro	ic50	0.0006	uM
7-[4-[4-(oxan-2-ylmethyl)piperazin-1-yl]-4-oxobutoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0007	uM
7-[4-(4-benzylpiperazin-1-yl)-4-oxobutoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0007	uM
7-[4-oxo-4-[4-(thiophen-2-ylmethyl)piperazin-1-yl]butoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0007	uM
7-[4-oxo-4-[4-(thiophen-3-ylmethyl)piperazin-1-yl]butoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0007	uM
N-(1-benzylpiperidin-4-yl)-4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanamide	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0007	uM
(4R)-4-methyl-3-[4-[[3-oxo-2-[[2-(trifluoromethyl)phenyl]methyl]cyclohexen-1-yl]amino]phenyl]-4,5-dihydro-1H-pyridazin-6-one	1797368: PDE SPA Enzyme Inhibition Assay from Article 10.1016/j.bmcl.2003.08.056: “Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors.”	ic50	0.0008	uM
4-methyl-3-[4-[[3-oxo-2-[[2-(trifluoromethyl)phenyl]methyl]cyclohexen-1-yl]amino]phenyl]-4,5-dihydro-1H-pyridazin-6-one	159499: Inhibitory concentration required to inhibit human phosphodiesterase 3A expressed in Escherichia coli	ic50	0.0008	uM
7-[3-[1-(1-benzylpiperidin-4-yl)tetrazol-5-yl]propoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one;hydrochloride	158575: Inhibition of human platelet aggregation cAMP PDE in vitro	ic50	0.0008	uM
7-[3-[1-[1-(2-ethylbutyl)piperidin-4-yl]tetrazol-5-yl]propoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one;hydrochloride	158575: Inhibition of human platelet aggregation cAMP PDE in vitro	ic50	0.0008	uM
7-[3-[1-[1-(cyclohexylmethyl)piperidin-4-yl]tetrazol-5-yl]propoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one;hydrochloride	158575: Inhibition of human platelet aggregation cAMP PDE in vitro	ic50	0.0008	uM
(4aS,8aR)-4-(3-chloro-4-methoxyphenyl)-2-cyclopentyl-4a,5,8,8a-tetrahydrophthalazin-1-one	2131352: Inhibition of human recombinant PDE3 expressed in Escherichia coli	ic50	0.0008	uM
Anagrelide	1952690: Inhibition of PDE3 (unknown origin)	ic50	0.0009	uM
phenyl 3-[cyclohexyl-[4-[(2-oxo-3,5-dihydro-1H-imidazo[2,1-b]quinazolin-7-yl)oxy]butanoyl]amino]propanoate	219850: In vivo inhibition of cyclic AMP phosphodiesterase from human platelets	ic50	0.0009	uM
7-[4-(4-cycloheptylpiperazin-1-yl)-4-oxobutoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0009	uM
7-[4-[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]-4-oxobutoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one	219160: Inhibition of human platelet c-AMP phosphodiesterase PDE 3	ic50	0.0009	uM
(4R)-3-[4-[[2-[(3-bromophenyl)methyl]-3-oxocyclohexen-1-yl]amino]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one	1797368: PDE SPA Enzyme Inhibition Assay from Article 10.1016/j.bmcl.2003.08.056: “Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors.”	ic50	0.0009	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	7
bisphenol A	decreases methylation, affects cotreatment, affects expression, increases abundance	2
trichostatin A	affects cotreatment, increases expression	2
mercuric bromide	affects cotreatment, increases expression	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	decreases methylation, increases methylation, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
OTX015	decreases expression	1
FR900359	decreases phosphorylation	1
mivebresib	decreases expression	1
ginger extract	affects expression, increases abundance, affects cotreatment	1
pirinixic acid	affects binding, increases activity, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	increases methylation	1
nickel sulfate	increases expression	1
coumarin	increases phosphorylation	1
trequinsin	decreases activity	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
pentanal	decreases expression	1
olprinone	decreases activity	1
chromium hexavalent ion	increases expression	1

ChEMBL screening assays

560 unique, capped per target: 531 binding, 14 admet, 12 functional, 3 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000423	Binding	Inhibition of PDE3 in human platelet	Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease. — J Med Chem
CHEMBL4348838	ADMET	Inhibition of PDE3 (unknown origin)	Structure Overhaul Affords a Potent Purine PI3Kδ Inhibitor with Improved Tolerability. — J Med Chem
CHEMBL759850	Functional	Inhibition of phosphodiesterase fraction III in anesthetized open chest dogs	Cardiotonic agents. Synthesis and inotropic activity of a series of isoquinolin-3-ol derivatives. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D6BJ	HyCyte HeLa KO-hPDE3A	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer