PDE3B

Summary

PDE3B (phosphodiesterase 3B, HGNC:8779) is a protein-coding gene on chromosome 11p15.2, encoding cGMP-inhibited 3’,5’-cyclic phosphodiesterase 3B (Q13370). Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological process.

Enables 3’,5’-cyclic-AMP phosphodiesterase activity. Involved in several processes, including negative regulation of angiogenesis; negative regulation of lipid catabolic process; and regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction. Located in membrane. Part of guanyl-nucleotide exchange factor complex.

Source: NCBI Gene 5140 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 214 total — 2 pathogenic
• Druggable target: yes — 41 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000922

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8779
Approved symbol	PDE3B
Name	phosphodiesterase 3B
Location	11p15.2
Locus type	gene with protein product
Status	Approved
Aliases	HcGIP1
Ensembl gene	ENSG00000152270
Ensembl biotype	protein_coding
OMIM	602047
Entrez	5140

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 15 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000282096, ENST00000455098, ENST00000525439, ENST00000532740, ENST00000534317, ENST00000870624, ENST00000870625, ENST00000870626, ENST00000870627, ENST00000870628, ENST00000870629, ENST00000870630, ENST00000870631, ENST00000931568, ENST00000931569, ENST00000964983, ENST00000964984, ENST00000964985

RefSeq mRNA: 5 — MANE Select: NM_000922 NM_000922, NM_001363569, NM_001363570, NM_001429699, NM_001429700

CCDS: CCDS7817, CCDS91445

Canonical transcript exons

ENST00000282096 — 16 exons

Exon	Start	End
ENSE00001004406	14789106	14789242
ENSE00001004407	14786437	14786685
ENSE00001004408	14830698	14830846
ENSE00001004409	14843827	14844026
ENSE00001004412	14867506	14867758
ENSE00001004413	14859043	14859246
ENSE00001004414	14819136	14819209
ENSE00001004415	14834982	14835095
ENSE00001004416	14861205	14861366
ENSE00001004417	14831640	14831777
ENSE00001004418	14832722	14832833
ENSE00001004419	14771937	14771987
ENSE00001262747	14643804	14645053
ENSE00001329007	14869461	14872044
ENSE00003534912	14818183	14818393
ENSE00003641705	14803944	14804050

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 92.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.9129 / max 652.2503, expressed in 987 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113203	5.8098	794
113202	4.1637	763
113206	0.6557	316
113205	0.6372	263
113212	0.3676	88
113201	0.3493	163
113204	0.2936	138
113208	0.2112	67
113207	0.1651	72
113211	0.1334	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	92.71	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.34	gold quality
adipose tissue	UBERON:0001013	88.21	gold quality
islet of Langerhans	UBERON:0000006	87.66	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.51	gold quality
connective tissue	UBERON:0002384	86.96	gold quality
calcaneal tendon	UBERON:0003701	86.92	gold quality
sigmoid colon	UBERON:0001159	86.42	gold quality
right lobe of liver	UBERON:0001114	84.16	gold quality
rectum	UBERON:0001052	84.14	gold quality
endothelial cell	CL:0000115	83.84	gold quality
colon	UBERON:0001155	83.75	gold quality
transverse colon	UBERON:0001157	83.45	gold quality
large intestine	UBERON:0000059	83.43	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.35	gold quality
liver	UBERON:0002107	83.16	gold quality
blood	UBERON:0000178	82.67	gold quality
omental fat pad	UBERON:0010414	82.65	gold quality
peritoneum	UBERON:0002358	82.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.47	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.41	gold quality
left ventricle myocardium	UBERON:0006566	82.10	gold quality
cerebellar hemisphere	UBERON:0002245	82.06	gold quality
descending thoracic aorta	UBERON:0002345	81.99	gold quality
cerebellar cortex	UBERON:0002129	81.93	gold quality
pancreas	UBERON:0001264	81.88	gold quality
right lung	UBERON:0002167	81.19	gold quality
intestine	UBERON:0000160	81.09	gold quality
vermiform appendix	UBERON:0001154	81.08	gold quality
cardiac muscle of right atrium	UBERON:0003379	80.85	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-46	yes	31.67
E-MTAB-5061	yes	30.33
E-CURD-122	yes	22.83
E-GEOD-81608	yes	19.99
E-GEOD-83139	yes	11.67
E-ENAD-27	yes	9.82
E-ANND-3	yes	6.58
E-CURD-119	yes	4.12
E-MTAB-7606	no	219.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARG

miRNA regulators (miRDB)

189 targeting PDE3B, 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-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478

Literature-anchored findings (GeneRIF, showing 21)

• Inhibition of PDE3B augments PDE4 inhibitor-induced apoptosis in a subset of patients with chronic lymphocytic leukemia (PMID:11839681)
• Results explain the dual cyclic AMP/cyclic GMP binding capabilities of phosphodiesterase 3B and provide the molecular basis for inhibitor specificity. (PMID:15147193)
• p87PIKAP is a novel regulatory subunit of phosphoinositide 3-kinase gamma that is highly expressed in heart and interacts with PDE3B [p87PIKAP] (PMID:16476736)
• Selective interaction between activated phosphodiesterase 3B and 14-3-3 proteins represents a mechanism by which cells can protect this enzyme from deactivation. (PMID:17255105)
• Cells can contain several non-overlapping PKA- and EPAC-based signaling complexes that allow PDE4D/PDE3B coordination of cell adhesion. (PMID:17884339)
• Findings demonstrate that PDE3B is present in human erythrocytes and are consistent with the hypothesis that PDE3 activity regulates cAMP levels associated with a signaling pathway activated by iloprost in these cells. (PMID:18586889)
• Data suggest that five novel genes, LUM, PDE3B, PDGF-C, NRG1 and PKD2, have great potential for predicting the efficacy of cisplatin-based chemotherapy against OSCC. (PMID:19569180)
• PDE3B is activated in response to agents relevant for beta-cell function and activation is linked to increased as well as decreased phosphorylation of the enzyme (PMID:21152070)
• PDE3B and EPAC1 bind directly through protein-protein interactions (PMID:21393242)
• PDE3B and the anti-lipolytic action of insulin may have a role in increased S-nitrosylation of adipose tissue in obesity (PMID:21724851)
• Rescue of low O(2)-induced ATP release from erythrocytes of type 2 diabetics by cilostazol restored the ability of erythrocytes to participate in the regulation of perfusion distribution in skeletal muscle. (PMID:21963837)
• PDE3B appears to be an important actor in regulation of energy metabolism and energy intake. Is inhibition of PDE3B a possible target for treatment of obesity or type 2 diabetes mellitus? [REVIEW] (PMID:22001403)
• Data indicate that genome-wide significant associations were found both at age 6 and 14 with single nucleotide polymorphisms (SNPs) on chromosome 11p15 in phosphodiesterase 3B, cGMP-inhibited protein PDE3B/cytochrome P-450 CYP2R1 genes. (PMID:25208829)
• Our results shed more light on phosphodiesterase 3A activation and could be relevant to the treatment of severe hypertension in the general population. (PMID:26283042)
• ABHD15 associates with and stabilizes phosphodiesterase 3B (PDE3B). (PMID:29768196)
• Phosphodiesterase 3B (PDE3B) antagonizes the anti-angiogenic actions of PKA in human and murine endothelial cells. (PMID:31176020)
• Impact of phosphodiesterases PDE3 and PDE4 on 5-hydroxytryptamine receptor4-mediated increase of cAMP in human atrial fibrillation. (PMID:32949251)
• In Vitro Inhibition of Phosphodiesterase 3B (PDE 3B) by Anthocyanin-Rich Fruit Juice Extracts and Selected Anthocyanins. (PMID:32967310)
• Phosphodiesterase 2A and 3B variants are associated with primary aldosteronism. (PMID:33112806)
• A novel link between circPDE3B and ferroptosis in esophageal squamous cell carcinoma progression. (PMID:38092323)
• PDE3B regulates KRT6B and increases the sensitivity of bladder cancer cells to copper ionophores. (PMID:38165426)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	pde3b	ENSDARG00000062190
mus_musculus	Pde3b	ENSMUSG00000030671
rattus_norvegicus	Pde3b	ENSRNOG00000011417
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), PDE1C (ENSG00000154678), PDE9A (ENSG00000160191), PDE7B (ENSG00000171408), PDE3A (ENSG00000172572), PDE4B (ENSG00000184588), PDE2A (ENSG00000186642), PDE7A (ENSG00000205268)

Protein

Protein identifiers

cGMP-inhibited 3’,5’-cyclic phosphodiesterase 3B — Q13370 (reviewed: Q13370)

Alternative names: CGIPDE1, Cyclic GMP-inhibited phosphodiesterase B

All UniProt accessions (1): Q13370

UniProt curated annotations — full annotation on UniProt →

Function. Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological process. Regulates angiogenesis by inhibiting the cAMP-dependent guanine nucleotide exchange factor RAPGEF3 and downstream phosphatidylinositol 3-kinase gamma-mediated signaling. Controls cardiac contractility by reducing cAMP concentration in cardiocytes.

Subunit / interactions. Homodimer. Interacts with PIK3CG; regulates PDE3B activity and thereby cAMP levels in cells. Interacts with RAPGEF3 and PIK3R6; form a signaling complex that regulates phosphatidylinositol 3-kinase gamma in angiogenesis. Interacts with ABHD15; this interaction regulates PDE3B’s stability and expression and, thereby, impacts the antilipolytic action of insulin.

Subcellular location. Membrane.

Tissue specificity. Abundant in adipose tissues.

Post-translational modifications. Phosphorylation at Ser-295 mediates insulin-induced activation of PDE3B.

Activity regulation. Inhibited by cGMP.

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13370-1	1	yes
Q13370-2	2

RefSeq proteins (5): NP_000913, NP_001350498, NP_001350499, NP_001416628, NP_001416629 (=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), 3 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)

UniProt features (76 total): helix 22, mutagenesis site 11, binding site 9, transmembrane region 6, region of interest 6, compositionally biased region 5, modified residue 4, strand 4, turn 3, chain 1, active site 1, splice variant 1, sequence variant 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1SO2	X-RAY DIFFRACTION	2.4
8SYC	X-RAY DIFFRACTION	2.7
9YUD	X-RAY DIFFRACTION	2.7
1SOJ	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13370-F1	64.10	0.31

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): 737 (proton donor)

Ligand- & substrate-binding residues (9): 737; 741; 821; 822; 822; 822; 937; 937; 988

Post-translational modifications (4): 13, 295, 296, 442

Mutagenesis-validated functional residues (11):

Position	Phenotype
2	loss of interaction with rapgef3.
3	loss of interaction with rapgef3.
6	loss of interaction with rapgef3.
8	loss of interaction with rapgef3.
9	loss of interaction with rapgef3.
10	loss of interaction with rapgef3.
12	loss of interaction with rapgef3.
439	loss of interaction with pik3r6.
440	loss of interaction with pik3r6.
445	loss of interaction with pik3r6.
449	loss of interaction with pik3r6.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-165160	PDE3B signalling
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 364 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, COUP_01, NFKB_Q6, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, TERAMOTO_OPN_TARGETS_CLUSTER_7, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, CEBP_Q2, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS

GO Biological Process (12): angiogenesis (GO:0001525), negative regulation of cell adhesion (GO:0007162), G protein-coupled receptor signaling pathway (GO:0007186), insulin receptor signaling pathway (GO:0008286), negative regulation of angiogenesis (GO:0016525), negative regulation of cell adhesion mediated by integrin (GO:0033629), regulation of angiogenesis (GO:0045765), negative regulation of lipid catabolic process (GO:0050995), regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051896), 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)

GO Molecular Function (8): 3’,5’-cyclic-nucleotide phosphodiesterase activity (GO:0004114), 3’,5’-cyclic-AMP phosphodiesterase activity (GO:0004115), protein kinase B binding (GO:0043422), metal ion binding (GO:0046872), 3’,5’-cyclic-GMP phosphodiesterase activity (GO:0047555), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), membrane (GO:0016020), guanyl-nucleotide exchange factor complex (GO:0032045)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
PKB-mediated events	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
angiogenesis	2
3’,5’-cyclic-nucleotide phosphodiesterase activity	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cell adhesion	1
regulation of cell adhesion	1
negative regulation of cellular process	1
G protein-coupled receptor activity	1
signal transduction	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
negative regulation of cell adhesion	1
cell adhesion mediated by integrin	1
regulation of cell adhesion mediated by integrin	1
regulation of anatomical structure morphogenesis	1
regulation of vasculature development	1
negative regulation of catabolic process	1
lipid catabolic process	1
negative regulation of lipid metabolic process	1
regulation of lipid catabolic process	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of intracellular signal transduction	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
cyclic-nucleotide phosphodiesterase activity	1

Protein interactions and networks

STRING

1058 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE3B	ABHD15	Q6UXT9	718
PDE3B	ALDH7A1	P49419	699
PDE3B	PIK3R6	Q5UE93	695
PDE3B	RAPGEF3	O95398	678
PDE3B	PIK3CG	P48736	665
PDE3B	PIK3R5	Q8WYR1	659
PDE3B	PDE4D	Q08499	598
PDE3B	AKAP1	Q92667	590
PDE3B	LIPE	Q05469	570
PDE3B	LEP	P41159	555
PDE3B	PRKACA	P17612	537
PDE3B	PRKACB	P22694	536
PDE3B	PRKACG	P22612	534
PDE3B	ZNF229	Q9UJW7	524
PDE3B	FOXP3	Q9BZS1	523

IntAct

105 interactions, top by confidence:

A	B	Type	Score
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
AKT1	AKT2	psi-mi:“MI:0914”(association)	0.640
RAPGEF3	PDE3B	psi-mi:“MI:0915”(physical association)	0.640
PDE3B	RAPGEF3	psi-mi:“MI:0915”(physical association)	0.640
RAPGEF3	PDE3B	psi-mi:“MI:0407”(direct interaction)	0.640
PDE3B	RAPGEF3	psi-mi:“MI:0407”(direct interaction)	0.640
PDE3B	RAPGEF3	psi-mi:“MI:0914”(association)	0.640
PDE3B	RAPGEF3	psi-mi:“MI:0403”(colocalization)	0.640
SLC16A3	CASK	psi-mi:“MI:0914”(association)	0.590
PDE3B	PIK3R6	psi-mi:“MI:0915”(physical association)	0.590
PIK3R6	PDE3B	psi-mi:“MI:0407”(direct interaction)	0.590
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
HPGDS	PDE3B	psi-mi:“MI:0915”(physical association)	0.560
PDE3B	LNX1	psi-mi:“MI:0915”(physical association)	0.560
AKT3	HSP90AA1	psi-mi:“MI:0914”(association)	0.560
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
KCNS3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TEX264	PER1	psi-mi:“MI:0914”(association)	0.530
LRRC8B	SLC25A17	psi-mi:“MI:0914”(association)	0.530
RNF170	ERLIN1	psi-mi:“MI:0914”(association)	0.530
PCDHAC2	TMEM223	psi-mi:“MI:0914”(association)	0.530
LRRTM1	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
SLC30A2	RER1	psi-mi:“MI:0914”(association)	0.530

BioGRID (169): PDE3B (Affinity Capture-MS), PDE3B (Affinity Capture-MS), PDE3B (Affinity Capture-MS), PDE3B (Affinity Capture-MS), PDE3B (Affinity Capture-MS), PDE3B (Affinity Capture-MS), PDE3B (Affinity Capture-MS), PDE3B (Affinity Capture-MS), PDE3B (Affinity Capture-MS), PDE3B (Affinity Capture-MS), PDE3B (Affinity Capture-MS), PDE3B (Affinity Capture-MS), PDE3B (Affinity Capture-MS), PDE3B (Affinity Capture-MS), PDE3B (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

8 interactions.

A	Effect	B	Mechanism
AKT1	up-regulates	PDE3B	phosphorylation
IKBKE	“up-regulates activity”	PDE3B	phosphorylation
AKT	up-regulates	PDE3B	phosphorylation
AKT	“up-regulates activity”	PDE3B	phosphorylation
AKT1	“up-regulates activity”	PDE3B	phosphorylation
PRKACA	unknown	PDE3B	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 111 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
Activation of BAD and translocation to mitochondria	7	67.5×	8e-10
Activation of BH3-only proteins	7	44.0×	2e-08
G beta:gamma signalling through PI3Kgamma	5	27.8×	4e-05
Intrinsic Pathway for Apoptosis	7	25.9×	7e-07
CD28 dependent PI3K/Akt signaling	5	24.9×	6e-05
FOXO-mediated transcription	5	21.3×	1e-04
Apoptosis	7	14.9×	2e-05
Programmed Cell Death	7	13.0×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
regulation of intracellular pH	6	36.9×	9e-06
intracellular zinc ion homeostasis	6	29.5×	2e-05
potassium ion transmembrane transport	7	9.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	165
Likely benign	19
Benign	9

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2751033	NM_024514.5(CYP2R1):c.882_897del (p.Thr294_Phe295insTer)	Pathogenic
977186	NM_024514.5(CYP2R1):c.124_137delinsCG (p.Gly42_Leu46delinsArg)	Pathogenic

SpliceAI

3631 predictions. Top by Δscore:

Variant	Effect	Δscore
11:14786549:G:GT	donor_gain	1.0000
11:14786550:GAGTA:G	donor_gain	1.0000
11:14786697:G:GG	donor_gain	1.0000
11:14803942:A:AG	acceptor_gain	1.0000
11:14803943:G:GG	acceptor_gain	1.0000
11:14818391:CAG:C	donor_gain	1.0000
11:14818391:CAGGT:C	donor_loss	1.0000
11:14818392:AGGTA:A	donor_loss	1.0000
11:14818394:G:GG	donor_gain	1.0000
11:14819126:A:AG	acceptor_gain	1.0000
11:14819131:A:AG	acceptor_gain	1.0000
11:14819132:T:G	acceptor_gain	1.0000
11:14819133:A:AG	acceptor_gain	1.0000
11:14819133:AAGCT:A	acceptor_gain	1.0000
11:14819135:GCT:G	acceptor_gain	1.0000
11:14830796:G:GT	donor_gain	1.0000
11:14830797:A:T	donor_gain	1.0000
11:14830803:A:G	donor_gain	1.0000
11:14830847:G:GG	donor_gain	1.0000
11:14831633:T:G	acceptor_gain	1.0000
11:14831639:GATT:G	acceptor_gain	1.0000
11:14831703:A:G	donor_gain	1.0000
11:14831761:G:GT	donor_gain	1.0000
11:14831762:A:T	donor_gain	1.0000
11:14831765:GATTC:G	donor_gain	1.0000
11:14831773:GTCAG:G	donor_gain	1.0000
11:14831774:TCAGG:T	donor_loss	1.0000
11:14831775:CAGGT:C	donor_loss	1.0000
11:14831777:GG:G	donor_loss	1.0000
11:14834980:A:AG	acceptor_gain	1.0000

AlphaMissense

7274 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:14843971:A:C	D822A	1.000
11:14843971:A:T	D822V	1.000
11:14843981:C:A	H825Q	1.000
11:14843981:C:G	H825Q	1.000
11:14843996:T:A	N830K	1.000
11:14843996:T:G	N830K	1.000
11:14844000:T:C	F832L	1.000
11:14844001:T:C	F832S	1.000
11:14844002:T:A	F832L	1.000
11:14844002:T:G	F832L	1.000
11:14844004:T:C	L833P	1.000
11:14859057:T:A	N845K	1.000
11:14859057:T:G	N845K	1.000
11:14859059:A:T	D846V	1.000
11:14859068:T:A	V849D	1.000
11:14859071:T:C	L850P	1.000
11:14859074:A:T	E851V	1.000
11:14859097:T:A	W859R	1.000
11:14859097:T:C	W859R	1.000
11:14861331:T:A	W951R	1.000
11:14861331:T:C	W951R	1.000
11:14861355:T:C	F959L	1.000
11:14861357:T:A	F959L	1.000
11:14861357:T:G	F959L	1.000
11:14867539:A:C	S974R	1.000
11:14867541:T:A	S974R	1.000
11:14867541:T:G	S974R	1.000
11:14867590:T:C	F991L	1.000
11:14867592:T:A	F991L	1.000
11:14867592:T:G	F991L	1.000

dbSNP variants (sampled 300 via entrez): RS1000007880 (11:14802935 T>C), RS1000013199 (11:14791172 A>G), RS1000015080 (11:14819338 C>T), RS1000048389 (11:14677747 C>T), RS1000064218 (11:14775243 C>T), RS1000077706 (11:14748345 C>T), RS1000079028 (11:14677489 A>G), RS1000079714 (11:14729081 C>T), RS1000089846 (11:14658886 A>C,G,T), RS1000093045 (11:14820819 C>T), RS1000102360 (11:14844151 T>A), RS1000129543 (11:14690885 A>G), RS1000172027 (11:14781345 C>G,T), RS1000184356 (11:14653964 C>A,T), RS1000189002 (11:14684263 A>G)

Disease associations

OMIM: gene MIM:602047 | disease phenotypes: MIM:600081

GenCC curated gene-disease

Mondo (1): vitamin D hydroxylation-deficient rickets, type 1B (MONDO:0010810)

Orphanet (1): Hypocalcemic vitamin D-dependent rickets (Orphanet:289157)

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST002602_11	Vitamin D levels	2.000000e-10
GCST002602_9	Vitamin D levels	4.000000e-08
GCST004518_4	Waist-to-hip ratio adjusted for body mass index	2.000000e-06
GCST004518_5	Waist-to-hip ratio adjusted for body mass index	3.000000e-08
GCST006611_15	HDL cholesterol	3.000000e-16
GCST006613_19	Triglycerides	1.000000e-08
GCST008103_53	Bipolar disorder	4.000000e-07
GCST009151_9	High density lipoprotein cholesterol levels	2.000000e-11
GCST009379_382	Type 2 diabetes	3.000000e-08
GCST009597_85	Multiple sclerosis	9.000000e-12
GCST009671_2	Serum 25-Hydroxyvitamin D levels	4.000000e-11
GCST010050_14	Adiponectin levels	1.000000e-07
GCST010244_136	Triglyceride levels	8.000000e-13
GCST012490_653	Femur bone mineral density x serum urate levels interaction	7.000000e-09
GCST90002385_195	High light scatter reticulocyte count	1.000000e-09
GCST90002397_565	Mean spheric corpuscular volume	3.000000e-13
GCST90002405_275	Reticulocyte count	5.000000e-13
GCST90002406_363	Reticulocyte fraction of red cells	6.000000e-10
GCST90020025_926	Waist-to-hip ratio adjusted for BMI	2.000000e-10
GCST90020026_788	Hip index	4.000000e-10
GCST90020027_1451	Waist-hip index	4.000000e-10
GCST90020028_1976	Hip circumference adjusted for BMI	7.000000e-10
GCST90020028_1977	Hip circumference adjusted for BMI	2.000000e-11
GCST90020028_1978	Hip circumference adjusted for BMI	3.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004502	adiponectin measurement
EFO:0004531	urate measurement
EFO:0007986	reticulocyte count
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564005	Vitamin D Hydroxylation-Deficient Rickets, Type 1B (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), CHEMBL290 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

41 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 351,741 (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
CHEMBL19449	IBUDILAST	4	7,461
CHEMBL2051955	LEVOSIMENDAN	3	3,145
CHEMBL19224	PAPAVERINE	3	22,172
CHEMBL12831	IMAZODAN	2	1,335
CHEMBL144399	MEDORINONE	2	384
CHEMBL153427	OXAGRELATE	2	1,107
CHEMBL17423	VESNARINONE	2	14,989
CHEMBL2110680	ISOMAZOLE	2	267
CHEMBL24646	PIMOBENDAN	2	4,695
CHEMBL286020	SULMAZOLE	2
CHEMBL29798	BEMARINONE	2
CHEMBL313136	SIMENDAN	2
CHEMBL313842	ZARDAVERINE	2
CHEMBL320341	QUAZINONE	2
CHEMBL34431	CILOSTAMIDE	2
CHEMBL356388	ETAZOLATE	2
CHEMBL3586573	CC-115	2
CHEMBL3654384	ORISMILAST	2
CHEMBL38224	INDOLIDAN	2

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

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 (5 total), top 5:

Ligand	Action	Affinity	Parameter
cilostamide	Inhibition	7.3	pIC50
cilostazol	Inhibition	6.42	pIC50
milrinone	Inhibition	6.0	pIC50
papaverine	Inhibition	5.99	pIC50
inamrinone	Inhibition	4.51	pIC50

Binding affinities (BindingDB)

109 measured of 125 human assays (154 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
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
2-[4-[3-(quinolin-6-ylmethyl)triazolo[4,5-b]pyrazin-5-yl]pyrazol-1-yl]ethanol	IC50	4 nM	US-9062045: Triazolopyridine compounds
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
2-[6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]quinolin-3-yl]-8-oxa-2-azaspiro[4.5]decane	IC50	5 nM	US-9062045: Triazolopyridine compounds
6-[[6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]sulfanyl]-N-(oxan-4-yl)quinolin-3-amine	IC50	5 nM	US-9062045: Triazolopyridine compounds
(NE)-N-[1-[3-(3-morpholin-4-ylquinolin-6-yl)sulfanyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl]ethylidene]hydroxylamine	IC50	5 nM	US-9062045: Triazolopyridine compounds
2-[4-[3-[3-(1-methylpyrazol-4-yl)quinolin-6-yl]sulfanyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl]pyrazol-1-yl]ethanol	IC50	5 nM	US-9062045: Triazolopyridine compounds
2-[(E)-1-[3-[[3-(4-methylpiperazin-1-yl)quinolin-6-yl]methyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]ethylideneamino]oxyethanol	IC50	6 nM	US-8507676: Heterocyclic oxime compounds

ChEMBL bioactivities

1197 potent at pChembl≥5 of 1480 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
10.31	IC50	0.049	nM	CHEMBL338860
10.17	IC50	0.068	nM	CHEMBL339210
10.10	IC50	0.08	nM	CHEMBL88787
10.00	IC50	0.1	nM	CHEMBL5081214
9.96	IC50	0.11	nM	CHEMBL131355
9.90	IC50	0.1259	nM	CHEMBL5080391
9.89	IC50	0.13	nM	CHEMBL131111
9.89	IC50	0.13	nM	CHEMBL129668
9.80	IC50	0.1585	nM	CHEMBL5087564
9.72	IC50	0.19	nM	CHEMBL128456
9.70	IC50	0.2	nM	CHEMBL90877
9.70	IC50	0.2	nM	CHEMBL329173
9.62	IC50	0.24	nM	CHEMBL338179
9.60	IC50	0.2512	nM	CHEMBL5094110
9.59	IC50	0.26	nM	CHEMBL128391
9.57	IC50	0.27	nM	CHEMBL131355
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
9.52	IC50	0.3	nM	CHEMBL128621
9.50	IC50	0.3162	nM	CHEMBL5086895
9.50	IC50	0.3162	nM	CHEMBL5076558
9.48	IC50	0.33	nM	CHEMBL129283
9.46	IC50	0.35	nM	CHEMBL338381
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
9.28	IC50	0.53	nM	CHEMBL130081
9.22	IC50	0.6	nM	CHEMBL91715
9.22	IC50	0.6	nM	CHEMBL91088
9.21	IC50	0.62	nM	CHEMBL130026
9.21	IC50	0.61	nM	CHEMBL131939
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
9.15	IC50	0.7	nM	CHEMBL341231
9.15	IC50	0.7	nM	CHEMBL129255
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

PubChem BioAssay actives

911 with measured affinity, of 2093 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
(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-[[2-[[2-(3-nitrophenyl)phenyl]methyl]-3-oxocyclohexen-1-yl]amino]phenyl]-4,5-dihydro-1H-pyridazin-6-one	159501: Inhibitory concentration required to inhibit human phosphodiesterase 3B expressed in Escherichia coli	ic50	<0.0001	uM
3-[4-[[2-[(2,6-dichlorophenyl)methyl]-3-oxocyclohexen-1-yl]amino]-2-fluorophenyl]-4,4-dimethyl-1H-pyrazol-5-one	159501: Inhibitory concentration required to inhibit human phosphodiesterase 3B expressed in Escherichia coli	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
3-[4-[[2-[(3-iodophenyl)methyl]-3-oxocyclohexen-1-yl]amino]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one	159501: Inhibitory concentration required to inhibit human phosphodiesterase 3B expressed in Escherichia coli	ic50	0.0001	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	0.0001	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-[[3-oxo-2-[(2-thiophen-3-ylphenyl)methyl]cyclohexen-1-yl]amino]phenyl]-4,5-dihydro-1H-pyridazin-6-one	159501: Inhibitory concentration required to inhibit human phosphodiesterase 3B expressed in Escherichia coli	ic50	0.0001	uM
3-[4-[[2-[(2-methoxyphenyl)methyl]-3-oxocyclohexen-1-yl]amino]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one	159501: Inhibitory concentration required to inhibit human phosphodiesterase 3B expressed in Escherichia coli	ic50	0.0001	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	0.0001	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
(4R)-3-[4-[(2-benzyl-3-oxocyclohexen-1-yl)amino]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one	159501: Inhibitory concentration required to inhibit human phosphodiesterase 3B expressed in Escherichia coli	ic50	0.0002	uM
3-[4-[(2-benzyl-3-oxocyclohexen-1-yl)amino]-2-fluorophenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one	159501: Inhibitory concentration required to inhibit human phosphodiesterase 3B expressed in Escherichia coli	ic50	0.0002	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
3-[[2-[4-(4,4-dimethyl-5-oxo-1H-pyrazol-3-yl)-2,3-difluoroanilino]-6-oxocyclohexen-1-yl]methyl]benzonitrile	159501: Inhibitory concentration required to inhibit human phosphodiesterase 3B expressed in Escherichia coli	ic50	0.0003	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
(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	0.0003	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	0.0003	uM
3-[4-[(2-benzyl-3-oxocyclohexen-1-yl)amino]-3-fluorophenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one	159501: Inhibitory concentration required to inhibit human phosphodiesterase 3B expressed in Escherichia coli	ic50	0.0003	uM
3-[4-[[2-[(3-bromophenyl)methyl]-3-oxocyclohexen-1-yl]amino]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one	159501: Inhibitory concentration required to inhibit human phosphodiesterase 3B expressed in Escherichia coli	ic50	0.0003	uM
4-methyl-3-[4-[[3-oxo-2-[[2-(trifluoromethyl)phenyl]methyl]cyclohexen-1-yl]amino]phenyl]-4,5-dihydro-1H-pyridazin-6-one	159501: Inhibitory concentration required to inhibit human phosphodiesterase 3B expressed in Escherichia coli	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
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
3-[4-[[2-[(2-chlorophenyl)methyl]-3-oxocyclohexen-1-yl]amino]-2-fluorophenyl]-4,4-dimethyl-1H-pyrazol-5-one	159501: Inhibitory concentration required to inhibit human phosphodiesterase 3B expressed in Escherichia coli	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
3-[4-[(2-benzyl-3-oxocyclohexen-1-yl)amino]-3-methylphenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one	159501: Inhibitory concentration required to inhibit human phosphodiesterase 3B expressed in Escherichia coli	ic50	0.0006	uM
3-[4-[(2-benzyl-3-oxocyclohexen-1-yl)amino]-2,5-difluorophenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one	159501: Inhibitory concentration required to inhibit human phosphodiesterase 3B expressed in Escherichia coli	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)-3-[4-[[2-[(3-fluorophenyl)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	0.0007	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects expression, decreases expression	4
bisphenol A	affects expression, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
alpha phellandrene	increases expression	1
cinnamaldehyde	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
trequinsin	decreases activity	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
Roflumilast	decreases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
L-826,141	decreases activity	1
candoxin	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	increases expression	1
PF-04254644	decreases activity	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1

ChEMBL screening assays

381 unique, capped per target: 367 binding, 9 functional, 5 admet

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

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B0ZY	Abcam MCF-7 PDE3B KO	Cancer cell line	Female
CVCL_B2A7	Abcam HeLa PDE3B KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06624657	Not specified	COMPLETED	High-intensity Interval Training and Vitamin D Effects on Bone Metabolism Among Women Diagnosed With Osteoporosis
NCT07275177	Not specified	COMPLETED	Effect of Vitamin D on Body Composition and Functionality of Older Adults
NCT07366450	Not specified	NOT_YET_RECRUITING	High-Dose vs Standard Ergocalciferol for Vitamin D Normalization in Aggressive Non-Hodgkin Lymphoma