PDE1C

Summary

PDE1C (phosphodiesterase 1C, HGNC:8776) is a protein-coding gene on chromosome 7p14.3, encoding Dual specificity calcium/calmodulin-dependent 3’,5’-cyclic nucleotide phosphodiesterase 1C (Q14123). Calmodulin-dependent cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.

This gene encodes an enzyme that belongs to the 3'5’-cyclic nucleotide phosphodiesterase family. Members of this family catalyze hydrolysis of the cyclic nucleotides, cyclic adenosine monophosphate and cyclic guanosine monophosphate, to the corresponding nucleoside 5’-monophosphates. The enzyme encoded by this gene regulates proliferation and migration of vascular smooth muscle cells, and neointimal hyperplasia. This enzyme also plays a role in pathological vascular remodeling by regulating the stability of growth factor receptors, such as PDGF-receptor-beta.

Source: NCBI Gene 5137 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant nonsyndromic hearing loss (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 29
• Clinical variants (ClinVar): 210 total — 3 likely-pathogenic
• Phenotypes (HPO): 4
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001191057

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8776
Approved symbol	PDE1C
Name	phosphodiesterase 1C
Location	7p14.3
Locus type	gene with protein product
Status	Approved
Aliases	Hcam3
Ensembl gene	ENSG00000154678
Ensembl biotype	protein_coding
OMIM	602987
Entrez	5137

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000321453, ENST00000396182, ENST00000396184, ENST00000396189, ENST00000396191, ENST00000396193, ENST00000464881, ENST00000478736, ENST00000479980, ENST00000482681, ENST00000495221, ENST00000672256, ENST00000856457, ENST00000952473, ENST00000952474

RefSeq mRNA: 10 — MANE Select: NM_001191057 NM_001191056, NM_001191057, NM_001191058, NM_001191059, NM_001322055, NM_001322056, NM_001322057, NM_001322058, NM_001322059, NM_005020

CCDS: CCDS5437, CCDS55099, CCDS55100

Canonical transcript exons

ENST00000396191 — 18 exons

Exon	Start	End
ENSE00001017114	32051554	32051580
ENSE00001123599	31775664	31775732
ENSE00001123622	31823073	31823248
ENSE00001123627	31824867	31824987
ENSE00001123631	31828292	31828373
ENSE00001123635	31837180	31837300
ENSE00001123640	31837870	31837971
ENSE00001123646	31847968	31848096
ENSE00001123649	31850641	31850741
ENSE00001123654	31864942	31865082
ENSE00001524194	32070293	32070407
ENSE00001524195	31751179	31753553
ENSE00003510335	31809031	31809108
ENSE00003544804	31815924	31816154
ENSE00003579816	31873292	31873408
ENSE00003584054	31878996	31879178
ENSE00003605247	31877970	31878036
ENSE00003679954	31880747	31880860

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 96.81.

FANTOM5 (CAGE): breadth broad, TPM avg 7.7620 / max 394.2065, expressed in 761 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83478	2.7636	593
83480	2.4880	353
83477	0.8433	319
83476	0.5379	247
83484	0.3847	144
83488	0.1441	59
83481	0.1222	64
83482	0.1207	53
83483	0.1023	44
83479	0.0952	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	96.81	gold quality
heart right ventricle	UBERON:0002080	96.65	gold quality
corpus callosum	UBERON:0002336	95.41	gold quality
apex of heart	UBERON:0002098	94.92	gold quality
cardiac ventricle	UBERON:0002082	93.77	gold quality
heart left ventricle	UBERON:0002084	93.68	gold quality
sural nerve	UBERON:0015488	93.59	gold quality
inferior vagus X ganglion	UBERON:0005363	92.90	gold quality
lateral globus pallidus	UBERON:0002476	92.44	gold quality
globus pallidus	UBERON:0001875	91.98	gold quality
medial globus pallidus	UBERON:0002477	91.50	gold quality
right atrium auricular region	UBERON:0006631	91.39	gold quality
cardiac atrium	UBERON:0002081	90.41	gold quality
heart	UBERON:0000948	90.29	gold quality
subthalamic nucleus	UBERON:0001906	90.15	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.84	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.60	gold quality
left uterine tube	UBERON:0001303	88.87	gold quality
spinal cord	UBERON:0002240	88.08	gold quality
postcentral gyrus	UBERON:0002581	87.65	gold quality
pons	UBERON:0000988	87.19	gold quality
parietal lobe	UBERON:0001872	87.11	gold quality
myocardium	UBERON:0002349	86.70	gold quality
substantia nigra pars compacta	UBERON:0001965	86.68	gold quality
left ventricle myocardium	UBERON:0006566	86.62	gold quality
superior vestibular nucleus	UBERON:0007227	86.12	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.63	gold quality
Ammon’s horn	UBERON:0001954	85.33	gold quality
ganglionic eminence	UBERON:0004023	85.31	gold quality
dorsal plus ventral thalamus	UBERON:0001897	85.03	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	3082.36
E-CURD-119	yes	2594.34
E-GEOD-180759	yes	2072.73
E-HCAD-35	yes	98.16
E-CURD-114	yes	10.44
E-GEOD-84465	yes	9.90
E-ANND-3	no	7.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

328 targeting PDE1C, 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-3163	100.00	77.23	8605
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487

Literature-anchored findings (GeneRIF, showing 7)

• PDE1C levels decreased in all conditions that inhibited proliferation (PMID:16455054)
• PDE1C1 is expressed at high levels in human cardiac myocytes with an intracellular distribution distinct from that of PDE3A (PMID:17726023)
• PDE1C is an important regulator of SMC proliferation, migration, and neointimal hyperplasia, in part through modulating endosome/lysosome-dependent PDGFRbeta protein degradation via low-density lipoprotein receptor-related protein-1. (PMID:25608528)
• PDE1C is a proliferation-associated gene in glioblastoma multiforme cells in vitro. (PMID:25620587)
• By combining population-specific mutation arrays, targeted deafness genes panel, whole exome sequencing (WES), we identified PDE1C (Phosphodiesterase 1C) c.958G>T (p.A320S) as the disease-associated variant. Structural modeling insights into p.A320S strongly suggest that the sequence alteration will likely affect the substrate-binding pocket of PDE1C. (PMID:29860631)
• Phosphodiesterase 1C integrates store-operated calcium entry and cAMP signaling in leading-edge protrusions of migrating human arterial myocytes. (PMID:33789162)
• Cyclic nucleotide phosphodiesterase 1C contributes to abdominal aortic aneurysm. (PMID:34312235)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	PDE1C	ENSDARG00000090398
mus_musculus	Pde1c	ENSMUSG00000004347
rattus_norvegicus	Pde1c	ENSRNOG00000012337
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), PDE9A (ENSG00000160191), PDE7B (ENSG00000171408), PDE3A (ENSG00000172572), PDE4B (ENSG00000184588), PDE2A (ENSG00000186642), PDE7A (ENSG00000205268)

Protein

Protein identifiers

Dual specificity calcium/calmodulin-dependent 3’,5’-cyclic nucleotide phosphodiesterase 1C — Q14123 (reviewed: Q14123)

Alternative names: Hcam3

All UniProt accessions (4): Q14123, A0A0A0MS69, A0A5F9ZGW6, F8W905

UniProt curated annotations — full annotation on UniProt →

Function. Calmodulin-dependent cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a high affinity for both cAMP and cGMP. Modulates the amplitude and duration of the cAMP signal in sensory cilia in response to odorant stimulation, hence contributing to the generation of action potentials. Regulates smooth muscle cell proliferation. Regulates the stability of growth factor receptors, including PDGFRB.

Subunit / interactions. Homodimer.

Subcellular location. Lysosome.

Tissue specificity. Isoform PDE1C2 is present in the heart and brain and, at lower levels in the lung, liver, kidney and skeletal muscle. Isoform PDE1C1 is expressed in the heart and brain and, at lower levels in lung. Also expressed at low levels in uterus and testis.

Disease relevance. Deafness, autosomal dominant, 74 (DFNA74) [MIM:618140] A form of non-syndromic deafness characterized by progressive, postlingual hearing loss with onset in the third decade of life. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Type I PDE are activated by the binding of calmodulin in the presence of Ca(2+).

Cofactor. Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions. Binds 2 divalent metal cations per subunit. Site 2 has a preference for magnesium ions.

Similarity. Belongs to the cyclic nucleotide phosphodiesterase family. PDE1 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q14123-1	PDE1C2, Hcam3a, PDE1C3, HSPDE1C3A, HSPDE1C3	yes
Q14123-2	PDE1C1, Hcam3b, HSPDE1C1A
Q14123-3	3

RefSeq proteins (10): NP_001177985, NP_001177986, NP_001177987, NP_001177988, NP_001308984, NP_001308985, NP_001308986, NP_001308987, NP_001308988, NP_005011 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002073	PDEase_catalytic_dom	Domain
IPR003607	HD/PDEase_dom	Domain
IPR013706	PDE1_N	Domain
IPR023088	PDEase	Family
IPR023174	PDEase_CS	Conserved_site
IPR036971	PDEase_catalytic_dom_sf	Homologous_superfamily

Pfam: PF00233, PF08499

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 (24 total): binding site 5, compositionally biased region 5, splice variant 3, region of interest 3, sequence conflict 3, chain 1, domain 1, active site 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14123-F1	71.53	0.45

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): 228 (proton donor)

Ligand- & substrate-binding residues (5): 232; 268; 269; 269; 376

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-111957	Cam-PDE 1 activation

MSigDB gene sets: 197 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, HORIUCHI_WTAP_TARGETS_DN, AREB6_03, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, TGCTGAY_UNKNOWN, BROWNE_HCMV_INFECTION_14HR_DN, TGACATY_UNKNOWN, KEGG_OLFACTORY_TRANSDUCTION, BROWNE_HCMV_INFECTION_24HR_DN, KEGG_PURINE_METABOLISM, YNGTTNNNATT_UNKNOWN, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, GOCC_CELL_BODY

GO Biological Process (2): signal transduction (GO:0007165), negative regulation of cAMP/PKA signal transduction (GO:0141162)

GO Molecular Function (9): 3’,5’-cyclic-AMP phosphodiesterase activity (GO:0004115), calmodulin-activated dual specificity 3’,5’-cyclic-GMP, 3’,5’-cyclic-AMP phosphodiesterase activity (GO:0004117), calmodulin binding (GO:0005516), metal ion binding (GO:0046872), 3’,5’-cyclic-GMP phosphodiesterase activity (GO:0047555), calmodulin-activated 3’,5’-cyclic-GMP phosphodiesterase activity (GO:0048101), 3’,5’-cyclic-nucleotide phosphodiesterase activity (GO:0004114), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (3): lysosome (GO:0005764), cytosol (GO:0005829), neuronal cell body (GO:0043025)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Calmodulin induced events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
3’,5’-cyclic-nucleotide phosphodiesterase activity	2
3’,5’-cyclic-GMP phosphodiesterase activity	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cAMP/PKA signal transduction	1
regulation of cAMP/PKA signal transduction	1
negative regulation of intracellular signal transduction	1
3’,5’-cyclic-AMP phosphodiesterase activity	1
protein binding	1
cation binding	1
cyclic-nucleotide phosphodiesterase activity	1
phosphoric ester hydrolase activity	1
catalytic activity	1
lytic vacuole	1
cytoplasm	1
cellular anatomical structure	1
somatodendritic compartment	1
cell body	1

Protein interactions and networks

STRING

864 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE1C	LHX6	Q9UPM6	890
PDE1C	ALDH7A1	P49419	889
PDE1C	CALM1	P02593	792
PDE1C	CALML3	P27482	735
PDE1C	CALML5	Q9NZT1	735
PDE1C	CALML6	Q8TD86	715
PDE1C	CALML4	Q96GE6	715
PDE1C	ADCY5	O95622	647
PDE1C	RAB2A	P08886	546
PDE1C	CNGA4	Q8IV77	541
PDE1C	LDB1	Q86U70	491
PDE1C	CNGA2	Q16280	472
PDE1C	ADORA2A	P29274	471
PDE1C	CCDC175	P0C221	460
PDE1C	ADCY3	O60266	453

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PDE1C	PDE1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): PDE1C (Affinity Capture-MS), PDE1A (Affinity Capture-MS), PDE1B (Affinity Capture-MS), GSPT2 (Affinity Capture-MS), PDE1C (Affinity Capture-MS), PDE1A (Affinity Capture-MS), GSPT2 (Affinity Capture-MS), PDE1B (Affinity Capture-MS), PDE1C (Affinity Capture-MS), CELF1 (Co-fractionation), PDE1C (Affinity Capture-MS), PDE1C (Affinity Capture-MS), PDE1C (Cross-Linking-MS (XL-MS)), PDE1C (Cross-Linking-MS (XL-MS)), PDE1C (Affinity Capture-MS)

ESM2 similar proteins: F1N2W9, F1QDI9, F1QMB9, O00763, O75909, O88874, O94776, P10276, P11416, P13631, P18514, P18911, P22605, P22681, P22682, P23798, P25500, P25916, P35227, P51003, Q13191, Q14123, Q3TTA7, Q5FBR4, Q5SDR3, Q61183, Q63421, Q640D5, Q64338, Q66JB6, Q69ZT9, Q6NRE7, Q7T3E6, Q7ZTI3, Q80TJ7, Q86UE8, Q8CFK2, Q8IU60, Q8JIR0, Q8K4S7

Diamond homologs: A0A077YBL0, B7YZV4, O18696, O60658, O88502, O89084, O95263, P06776, P12252, P14100, P14270, P14644, P14646, P27815, P30645, P54748, P54750, Q01061, Q01063, Q01064, Q01065, Q01066, Q07343, Q08493, Q08499, Q14123, Q3UEI1, Q61481, Q63421, Q64338, Q64395, Q6NNF2, Q86H13, Q8I5V4, Q8IRU4, Q9I7S6, Q9N2V9, Q9W4S9, Q9W4T4, B0G0Y8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
3-isobutyl-1-methyl-7H-xanthine	“down-regulates activity”	PDE1C	“chemical inhibition”
PDE1C	“down-regulates quantity”	“3’,5’-cyclic AMP”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	105
Likely benign	21
Benign	57

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3250393	NM_001191057.4(PDE1C):c.1900C>T (p.Gln634Ter)	Likely pathogenic
3250394	NM_001191057.4(PDE1C):c.2061C>A (p.Tyr687Ter)	Likely pathogenic
4070944	NM_001191058.4(PDE1C):c.86-1G>A	Likely pathogenic

SpliceAI

5025 predictions. Top by Δscore:

Variant	Effect	Δscore
7:31809025:TCTTA:T	donor_loss	1.0000
7:31809026:CTTA:C	donor_loss	1.0000
7:31809027:TTAC:T	donor_loss	1.0000
7:31809028:TACCA:T	donor_loss	1.0000
7:31809029:A:AC	donor_gain	1.0000
7:31809030:C:A	donor_loss	1.0000
7:31809030:C:CC	donor_gain	1.0000
7:31809030:CCAT:C	donor_gain	1.0000
7:31809109:C:CC	acceptor_gain	1.0000
7:31816150:CTCCT:C	acceptor_gain	1.0000
7:31816151:TCCT:T	acceptor_gain	1.0000
7:31816152:CCTC:C	acceptor_gain	1.0000
7:31816153:CT:C	acceptor_gain	1.0000
7:31816155:C:CC	acceptor_gain	1.0000
7:31816162:C:CT	acceptor_gain	1.0000
7:31816167:CAAGT:C	acceptor_gain	1.0000
7:31816168:A:T	acceptor_gain	1.0000
7:31816171:T:C	acceptor_gain	1.0000
7:31816171:T:TC	acceptor_gain	1.0000
7:31816181:C:CT	acceptor_gain	1.0000
7:31816181:C:T	acceptor_gain	1.0000
7:31816183:C:CT	acceptor_gain	1.0000
7:31816184:A:T	acceptor_gain	1.0000
7:31823244:TCAAA:T	acceptor_gain	1.0000
7:31823245:CAAA:C	acceptor_gain	1.0000
7:31823245:CAAAC:C	acceptor_gain	1.0000
7:31823246:AAA:A	acceptor_gain	1.0000
7:31823249:C:CC	acceptor_gain	1.0000
7:31824925:CAAT:C	donor_gain	1.0000
7:31824984:AAACC:A	acceptor_loss	1.0000

AlphaMissense

4688 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:31823092:C:A	W521C	1.000
7:31823092:C:G	W521C	1.000
7:31823094:A:G	W521R	1.000
7:31823094:A:T	W521R	1.000
7:31824972:A:C	I434S	1.000
7:31824972:A:T	I434N	1.000
7:31824974:G:C	F433L	1.000
7:31824974:G:T	F433L	1.000
7:31824976:A:G	F433L	1.000
7:31824983:G:C	F430L	1.000
7:31824983:G:T	F430L	1.000
7:31824984:A:C	F430C	1.000
7:31824984:A:G	F430S	1.000
7:31824985:A:C	F430V	1.000
7:31824985:A:G	F430L	1.000
7:31824985:A:T	F430I	1.000
7:31828296:T:A	Q427H	1.000
7:31828296:T:G	Q427H	1.000
7:31828329:A:C	C416W	1.000
7:31828330:C:T	C416Y	1.000
7:31828331:A:G	C416R	1.000
7:31828333:A:G	L415P	1.000
7:31828333:A:T	L415Q	1.000
7:31828348:A:G	L410P	1.000
7:31828362:T:A	E405D	1.000
7:31828362:T:G	E405D	1.000
7:31828372:C:A	G402V	1.000
7:31828372:C:T	G402D	1.000
7:31828373:C:A	G402C	1.000
7:31828373:C:G	G402R	1.000

dbSNP variants (sampled 300 via entrez): RS1000002874 (7:32039144 T>A,C), RS1000003265 (7:32210527 A>T), RS1000003515 (7:32206410 A>G), RS1000013331 (7:31682327 C>T), RS1000018462 (7:32327233 T>G), RS1000021771 (7:31750040 T>G), RS1000026498 (7:32376319 G>A), RS1000030355 (7:32035844 G>A), RS1000031455 (7:32406187 C>A), RS1000037610 (7:32004519 T>C), RS1000039091 (7:31760926 C>T), RS1000041876 (7:32088500 A>C,G), RS1000049668 (7:31749680 C>A), RS1000049890 (7:31664231 T>C), RS1000056786 (7:32120301 C>T)

Disease associations

OMIM: gene MIM:602987 | disease phenotypes: MIM:618140, MIM:143890, MIM:124900

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant
hearing loss, autosomal dominant 74	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autosomal dominant nonsyndromic hearing loss	Limited	AD

Mondo (4): hearing loss, autosomal dominant 74 (MONDO:0029137), prostate cancer (MONDO:0008315), hypercholesterolemia, familial, 1 (MONDO:0007750), autosomal dominant nonsyndromic hearing loss (MONDO:0019587)

Orphanet (3): Familial prostate cancer (Orphanet:1331), Homozygous familial hypercholesterolemia (Orphanet:391665), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000407	Sensorineural hearing impairment
HP:0001751	Abnormal vestibular function
HP:0003581	Adult onset

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST001356_33	Gout	1.000000e-07
GCST001872_7	Presence of antiphospholipid antibodies	3.000000e-06
GCST001894_10	Endometriosis	1.000000e-06
GCST003498_3	Verbal-numerical reasoning	4.000000e-08
GCST004364_21	Intelligence	1.000000e-10
GCST004364_3	Intelligence	4.000000e-08
GCST004904_262	Body mass index	3.000000e-08
GCST005141_60	Cognitive ability (MTAG)	3.000000e-12
GCST005142_13	Cognitive ability	2.000000e-10
GCST005142_14	Cognitive ability	3.000000e-10
GCST005316_49	Intelligence (MTAG)	9.000000e-10
GCST005316_50	Intelligence (MTAG)	4.000000e-08
GCST007044_16	Extremely high intelligence	2.000000e-09
GCST007565_166	Morning person	2.000000e-15
GCST007565_52	Morning person	8.000000e-20
GCST007576_349	Chronotype	8.000000e-20
GCST007932_115	Medication use (thyroid preparations)	2.000000e-08
GCST008803_4	Smoking behaviour (cigarette pack-years)	3.000000e-16
GCST008809_3	Smoking behaviour (cigarettes smoked per day)	1.000000e-10
GCST009310_9	Sensorimotor dexterity	4.000000e-06
GCST009823_13	Gynecologic disease (multivariate analysis)	3.000000e-09
GCST010244_199	Triglyceride levels	1.000000e-08
GCST010396_256	Gut microbiota (bacterial taxa, hurdle binary method)	2.000000e-07
GCST010396_81	Gut microbiota (bacterial taxa, hurdle binary method)	9.000000e-07
GCST010988_152	Adult body size	1.000000e-13
GCST011126_15	Caffeine consumption from coffee or tea	6.000000e-10
GCST011702_9	Smoking cessation	4.000000e-08
GCST90000047_137	Age at first sexual intercourse	4.000000e-09
GCST90000514_10	Gastroesophageal reflux disease	4.000000e-11

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004350	reasoning
EFO:0004337	intelligence
EFO:0004340	body mass index
EFO:0004784	self reported educational attainment
EFO:0008328	chronotype measurement
EFO:0009933	Thyroid preparation use measurement
EFO:0009115	tobacco smoke exposure measurement
EFO:0006525	cigarettes per day measurement
EFO:0008354	cognitive function measurement
EFO:0004530	triglyceride measurement
EFO:0007874	gut microbiome measurement
EFO:0006781	coffee consumption measurement
EFO:0010091	tea consumption measurement
EFO:0004319	smoking cessation
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2095150 (PROTEIN FAMILY), CHEMBL2097161 (PROTEIN FAMILY), CHEMBL2363066 (PROTEIN FAMILY), CHEMBL4619 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 252,749 (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
CHEMBL1520	VARDENAFIL	4	21,078
CHEMBL192	SILDENAFIL	4	41,819
CHEMBL71752	VINPOCETINE	4	8,194
CHEMBL932	DIPYRIDAMOLE	4	51,743
CHEMBL1428	NIMODIPINE	4	32,587
CHEMBL19224	PAPAVERINE	3	22,172
CHEMBL475534	NITRENDIPINE	3	16,468
CHEMBL150764	BUFROLIN	2	131
CHEMBL153427	OXAGRELATE	2	1,107
CHEMBL28079	ZAPRINAST	2	16,158
CHEMBL34431	CILOSTAMIDE	2	3,222
CHEMBL356388	ETAZOLATE	2	1,934
CHEMBL6318	IDOXIFENE	2	16,390
CHEMBL63	ROLIPRAM	2	19,520
CHEMBL2179105	EDELINONTRINE	2	226

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 (4 total), top 4:

Ligand	Action	Affinity	Parameter
compound 3m [PMID: 32603117]	Inhibition	8.54	pIC50
Lu AF64196	Inhibition	7.33	pKi
SCH51866	Inhibition	7.2	pIC50
vinpocetine	Inhibition	4.3	pIC50

Binding affinities (BindingDB)

190 measured of 199 human assays (199 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-(2-ethoxy-3-pyridyl)-3-methyl-N-[(1-methylimidazol-4-yl)methyl]-1-[1-methylpropyl]pyrazolo[4,3-b]pyridin-7-amine,enantiomer 2	IC50	0.14 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
1-isopropyl-3-methyl-N-[(1-methylimidazol-4-yl)methyl]-5-(2-propoxy-3-pyridyl)pyrazolo[4,3-b]pyridin-7-amine	IC50	0.26 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-3-methyl-1-[1-methylpropyl]-N-[(5-methyl-1H-pyrazol-3-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine,enantiomer 2	IC50	0.35 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
N-[(1,5-dimethylpyrazol-3-yl)methyl]-5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-pyrazolo[4,3-b]pyridin-7-amine	IC50	0.39 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
1-isopropyl-3-methyl-N-[(1-methyl-1,2,4-triazol-3-yl)methyl]-5-(2-propoxy-3-pyridyl)pyrazolo[4,3-b]pyridin-7-amine	IC50	0.41 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(5-methylthiazol-2-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	0.46 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-(2H-tetrazol-5-ylmethyl)pyrazolo[4,3-b]pyridin-7-amine	IC50	0.73 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
3-methyl-1-[1-methylpropyl]-N-[(2-methyltetrazol-5-yl)methyl]-5-(2-propoxy-3-pyridyl)pyrazolo[4,3-b]pyridin-7-amine,enantiomer 2	IC50	0.79 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(5-methylisoxazol-3-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	0.8 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
3-methyl-1-[1-methylpropyl]-N-[(1-methyl-1,2,4-triazol-3-yl)methyl]-5-(2-propoxy-3-pyridyl)pyrazolo[4,3-b]pyridin-7-amine,enantiomer 2	IC50	0.96 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-N-[(4-methoxy-2-pyridyl)methyl]-3-methyl-pyrazolo[4,3-b]pyridin-7-amine	IC50	1 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-N-[(5-methoxy-3-pyridyl)methyl]-3-methyl-1-[1-methylpropyl]pyrazolo[4,3-b]pyridin-7-amine,enantiomer 2	IC50	1 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(5-methyloxazol-2-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	1.1 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxypyridin-3-yl)-1-isopropyl-3-methyl-N-((1-methyl-1H-imidazol-4-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine 2,2,2-trifluoroacetate	IC50	1.1 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(1-methyl-1,2,4-triazol-3-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	1.2 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-3-methyl-N-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-1-[1-methylpropyl]pyrazolo[4,3-b]pyridin-7-amine,enantiomer 2	IC50	1.2 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
1-isopropyl-3-methyl-N-[(1-methylpyrazol-4-yl)methyl]-5-(2-propoxy-3-pyridyl)pyrazolo[4,3-b]pyridin-7-amine	IC50	1.4 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-isopropoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(1-methylpyrazol-4-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	1.4 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	1.6 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxypyridin-3-yl)-1-isopropyl-3-methyl-N-((5-methyl-1H-pyrazol-3-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine	IC50	1.6 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-3-methyl-1-[1-methylpropyl]-N-[(2-methyltetrazol-5-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine,enantiomer 2	IC50	1.8 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	1.9 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
3-methyl-1-[1-methylpropyl]-5-(2-propoxy-3-pyridyl)-N-(1H-pyrazol-3-ylmethyl)pyrazolo[4,3-b]pyridin-7-amine,enantiomer 2	IC50	1.9 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-(pyrimidin-2-ylmethyl)pyrazolo[4,3-b]pyridin-7-amine	IC50	2.1 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-N-[(5-methoxy-3-pyridyl)methyl]-3-methyl-pyrazolo[4,3-b]pyridin-7-amine	IC50	2.1 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-N-[[5-(fluoromethyl)isoxazol-3-yl]methyl]-1-isopropyl-3-methyl-pyrazolo[4,3-b]pyridin-7-amine	IC50	2.1 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-N-[(2-methoxy-4-pyridyl)methyl]-3-methyl-pyrazolo[4,3-b]pyridin-7-amine	IC50	2.2 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-3-methyl-1-[1-methylpropyl]-N-[(1-methyl-1,2,4-triazol-3-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine,enantiomer 1	IC50	2.2 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxypyridin-3-yl)-1-isopropyl-3-methyl-N-((1-methyl-1H-pyrazol-4-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine	IC50	2.6 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
3-[[[5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-pyrazolo[4,3-b]pyridin-7-yl]amino]methyl]-1-methyl-pyridin-2-one	IC50	2.8 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-N-[(6-methoxypyrimidin-4-yl)methyl]-3-methyl-pyrazolo[4,3-b]pyridin-7-amine	IC50	2.8 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(2-methyltetrazol-5-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	2.9 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(5-methyl-1H-1,2,4-triazol-3-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	3.4 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
1-isopropyl-3-methyl-5-(2-propoxy-3-pyridyl)-N-(1H-pyrazol-3-ylmethyl)pyrazolo[4,3-b]pyridin-7-amine	IC50	3.8 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
1-isopropyl-3-methyl-5-(2-propoxy-3-pyridyl)-N-(1H-1,2,4-triazol-3-ylmethyl)pyrazolo[4,3-b]pyridin-7-amine	IC50	3.9 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-N-[(4-methoxypyrimidin-2-yl)methyl]-3-methyl-pyrazolo[4,3-b]pyridin-7-amine	IC50	3.9 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(3-methylisoxazol-5-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	4.1 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
1-isopropyl-3-methyl-N-[(2-methyltetrazol-5-yl)methyl]-5-(2-propoxy-3-pyridyl)pyrazolo[4,3-b]pyridin-7-amine	IC50	4.3 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(2-methylthiazol-5-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	4.6 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-3-methyl-1-[1-methylpropyl]-N-(1H-pyrazol-3-ylmethyl)pyrazolo[4,3-b]pyridin-7-amine,enantiomer 1	IC50	4.6 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(1-methyltriazol-4-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	4.8 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-N-[(1-ethylpyrazol-4-yl)methyl]-1-isopropyl-3-methyl-pyrazolo[4,3-b]pyridin-7-amine	IC50	4.9 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxypyridin-3-yl)-1-isopropyl-3-methyl-N-((2-methyl-1H-imidazol-4-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine	IC50	5 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(2-methyl-4-pyridyl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	5.4 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-N-[(2-methoxy-4-pyridyl)methyl]-3-methyl-1-[1-methylpropyl]pyrazolo[4,3-b]pyridin-7-amine,enantiomer 2	IC50	5.4 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(2-methyloxazol-4-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	5.9 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(6-methyl-3-pyridyl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	6.3 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-(2-pyridylmethyl)pyrazolo[4,3-b]pyridin-7-amine	IC50	6.3 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(1-methylpyrazol-3-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine	IC50	6.5 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors
5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-7-[(1-methylpyrazol-4-yl)methylsulfanyl]pyrazolo[4,3-b]pyridine	IC50	6.8 nM	US-10034861: 1H-pyrazolo[4,3-b]pyridines as PDE1 inhibitors

ChEMBL bioactivities

2308 potent at pChembl≥5 of 2425 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL5081214
9.90	IC50	0.1259	nM	CHEMBL5080391
9.85	IC50	0.14	nM	CHEMBL5572993
9.80	IC50	0.1585	nM	CHEMBL5087564
9.60	IC50	0.2512	nM	CHEMBL5094110
9.50	IC50	0.3162	nM	CHEMBL5086895
9.50	IC50	0.3162	nM	CHEMBL5076558
9.40	IC50	0.4	nM	CHEMBL572934
9.40	IC50	0.4	nM	CHEMBL6057973
9.40	IC50	0.396	nM	CHEMBL5977186
9.39	IC50	0.406	nM	CHEMBL6005179
9.38	IC50	0.419	nM	CHEMBL6042932
9.34	IC50	0.46	nM	CHEMBL5990945
9.34	IC50	0.46	nM	CHEMBL5856741
9.34	IC50	0.46	nM	CHEMBL6062258
9.28	IC50	0.52	nM	CHEMBL5959210
9.28	IC50	0.52	nM	CHEMBL5843142
9.28	IC50	0.52	nM	CHEMBL5872664
9.10	IC50	0.8	nM	CHEMBL5912826
9.10	IC50	0.8	nM	CHEMBL5874788
9.05	IC50	0.9	nM	CHEMBL4639341
9.03	IC50	0.928	nM	CHEMBL5773878
9.02	IC50	0.958	nM	CHEMBL5906866
9.00	IC50	1	nM	CHEMBL5078680
9.00	IC50	1	nM	CHEMBL5088742
8.97	IC50	1.06	nM	CHEMBL5758304
8.95	IC50	1.13	nM	CHEMBL5908735
8.92	IC50	1.2	nM	CHEMBL6024984
8.92	IC50	1.2	nM	CHEMBL5872827
8.90	IC50	1.26	nM	CHEMBL6038903
8.89	IC50	1.3	nM	CHEMBL6064474
8.89	IC50	1.3	nM	CHEMBL5874494
8.89	IC50	1.3	nM	CHEMBL5866510
8.85	IC50	1.4	nM	CHEMBL6033946
8.83	IC50	1.49	nM	CHEMBL5760003
8.82	IC50	1.5	nM	CHEMBL4640793
8.82	IC50	1.5	nM	CHEMBL5843130
8.82	IC50	1.5	nM	CHEMBL5771846
8.74	IC50	1.8	nM	CHEMBL5943853
8.73	IC50	1.88	nM	CHEMBL6019022
8.70	IC50	2	nM	CHEMBL5984308
8.68	IC50	2.1	nM	CHEMBL5740051
8.68	IC50	2.1	nM	CHEMBL5996697
8.68	IC50	2.1	nM	CHEMBL572934
8.67	IC50	2.138	nM	CHEMBL572934
8.64	IC50	2.3	nM	CHEMBL5543054
8.62	IC50	2.41	nM	CHEMBL6062186
8.62	IC50	2.4	nM	CHEMBL5840762
8.60	IC50	2.5	nM	CHEMBL5575643
8.59	IC50	2.6	nM	CHEMBL4647278

PubChem BioAssay actives

313 with measured affinity, of 1060 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
1-(1-cyclopropylcyclopropyl)-5-(cyclopropylmethyl)-6,7,8,9-tetrahydro-[1,2,4]triazolo[4,3-a]quinoxalin-4-one	2096270: Inhibition of PDE1C (unknown origin) expressed in Escherichia coli BL21 using [3H]cGMP as substrate incubated for 15 mins by liquid scintillation method	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
[(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
[(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
6-benzyl-1-cyclopentyl-5H-pyrazolo[5,4-d]pyrimidin-4-one	708595: Inhibition of human recombinant PDE1C expressed in Sf9 cells using [3H]cAMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0004	uM
5-benzyl-6-[[(1R)-1-(4-chlorophenyl)ethyl]amino]-1-propan-2-ylpyrazolo[5,4-d]pyrimidin-4-one	1652890: Inhibition of PDE1C2 (147 to 531 residues) (unknown origin) using [3H]-cGMP substrate incubated for 15 mins by liquid scintillation counting method	ic50	0.0009	uM
[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)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	0.0010	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]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0010	uM
5-benzyl-1-tert-butyl-6-[[(1R)-1-(4-chlorophenyl)ethyl]amino]pyrazolo[5,4-d]pyrimidin-4-one	1652890: Inhibition of PDE1C2 (147 to 531 residues) (unknown origin) using [3H]-cGMP substrate incubated for 15 mins by liquid scintillation counting method	ic50	0.0015	uM
bis(cyclohexylmethyl) 4-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-6-methyl-2-oxo-1,4-dihydropyrimidine-3,5-dicarboxylate	2070777: Inhibition of PDE1C2 (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0023	uM
1-tert-butyl-6-[[(1R)-1-(4-chlorophenyl)ethyl]amino]-5-[(3-fluorophenyl)methyl]pyrazolo[5,4-d]pyrimidin-4-one	2096270: Inhibition of PDE1C (unknown origin) expressed in Escherichia coli BL21 using [3H]cGMP as substrate incubated for 15 mins by liquid scintillation method	ic50	0.0025	uM
5-benzyl-1-tert-butyl-6-[[(1R)-1-(4-fluorophenyl)ethyl]amino]pyrazolo[5,4-d]pyrimidin-4-one	1652890: Inhibition of PDE1C2 (147 to 531 residues) (unknown origin) using [3H]-cGMP substrate incubated for 15 mins by liquid scintillation counting method	ic50	0.0026	uM
1-tert-butyl-6-[[(1R)-1-(4-chlorophenyl)ethyl]amino]-5-[(4-fluorophenyl)methyl]pyrazolo[5,4-d]pyrimidin-4-one	1652890: Inhibition of PDE1C2 (147 to 531 residues) (unknown origin) using [3H]-cGMP substrate incubated for 15 mins by liquid scintillation counting method	ic50	0.0029	uM
15,15-difluoro-8-[(4-methoxyphenyl)methyl]-13-(oxan-4-ylmethyl)-10-thia-3,5,6,8,13-pentazatetracyclo[7.7.0.02,6.011,16]hexadeca-1(9),2,4,11(16)-tetraen-7-one	1923539: Inhibition of PDE1 (unknown origin)	ic50	0.0030	uM
5-[(3-chlorophenyl)methyl]-3-propan-2-yl-2,6-dihydropyrazolo[4,3-d]pyrimidin-7-one	352681: Inhibition of PDE1c	ic50	0.0040	uM
1-tert-butyl-5-[(3-fluorophenyl)methyl]-6-[(5-fluoro-2-pyridinyl)methylamino]pyrazolo[5,4-d]pyrimidin-4-one	2096270: Inhibition of PDE1C (unknown origin) expressed in Escherichia coli BL21 using [3H]cGMP as substrate incubated for 15 mins by liquid scintillation method	ic50	0.0045	uM
5-benzyl-6-[[(1R)-1-(4-chlorophenyl)ethyl]amino]-1-cyclopentylpyrazolo[5,4-d]pyrimidin-4-one	1652890: Inhibition of PDE1C2 (147 to 531 residues) (unknown origin) using [3H]-cGMP substrate incubated for 15 mins by liquid scintillation counting method	ic50	0.0047	uM
cyclohexylmethyl 4-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-6-methyl-2-oxo-3-phenoxycarbothioyl-1,4-dihydropyrimidine-5-carboxylate	2070777: Inhibition of PDE1C2 (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0058	uM
bis(cyclohexylmethyl) 4-(3,4-dimethoxyphenyl)-6-methyl-2-oxo-1,4-dihydropyrimidine-3,5-dicarboxylate	2070777: Inhibition of PDE1C2 (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0059	uM
bis(cyclohexylmethyl) 4-[3,4-bis(difluoromethoxy)phenyl]-6-methyl-2-oxo-1,4-dihydropyrimidine-3,5-dicarboxylate	2070777: Inhibition of PDE1C2 (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0075	uM
2-[4-[3-ethyl-4-[3-(naphthalen-1-ylmethyl)phenyl]phenyl]-3-propan-2-ylphenoxy]acetic acid	45096: Inhibition of calmodulin-dependent PDE(3’,5’-phosphodiesterase)	ic50	0.0090	uM
7-cyclopentyl-2-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-5-methyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one	240757: Inhibition of phosphodiesterase 1	ic50	0.0100	uM
7-cyclopentyl-2-[2-ethoxy-5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonylphenyl]-5-methyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one	240757: Inhibition of phosphodiesterase 1	ic50	0.0100	uM
2-(2-ethoxyphenyl)-9-propyl-1H-purin-6-one	240757: Inhibition of phosphodiesterase 1	ic50	0.0100	uM
3-cyclopentyl-5-[2-ethoxy-5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonylphenyl]-1-methyl-6H-pyrazolo[4,5-d]pyrimidin-7-one	240757: Inhibition of phosphodiesterase 1	ic50	0.0100	uM
bis[(1R)-1-phenylethyl] 2,6-dimethyl-4-(1-methylindazol-5-yl)-1,4-dihydropyridine-3,5-dicarboxylate	1912032: Inhibition of PDE1C (147 to 531 residues) (unknown origin) expressed in Escherichia coli BL21 using [3H]-cGMP as substrate measured for 15 mins by liquid scintillation counter method	ic50	0.0100	uM
cyclohexylmethyl 3-benzylsulfanylcarbonyl-4-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-6-methyl-2-oxo-1,4-dihydropyrimidine-5-carboxylate	2070777: Inhibition of PDE1C2 (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0100	uM
3-anilino-5-methyl-7-(2-methylpropyl)-2-[[4-(1-methylpyrrolidin-2-yl)phenyl]methyl]pyrazolo[3,4-d]pyrimidine-4,6-dione	1924472: Inhibition of PDE1 (unknown origin)	ic50	0.0130	uM
6-benzyl-1-(oxan-4-yl)-5H-pyrazolo[5,4-d]pyrimidin-4-one	708595: Inhibition of human recombinant PDE1C expressed in Sf9 cells using [3H]cAMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0140	uM
4-cyclopentyl-1-(cyclopentylmethyl)-7-[(5-fluoro-2-pyridinyl)methylamino]-2-oxoquinoline-3-carbonitrile	1971458: Inhibition of PDE1C (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0150	uM
1-benzyl-4-(4-methylphenyl)-2-oxo-7-(1-pyridin-2-ylethylamino)quinoline-3-carbonitrile	1971458: Inhibition of PDE1C (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0150	uM
4-cyclopentyl-1-(cyclopentylmethyl)-2-oxo-7-[[(1S)-1-pyridin-2-ylethyl]amino]quinoline-3-carbonitrile	1971458: Inhibition of PDE1C (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0160	uM
4-cyclopentyl-1-(cyclopentylmethyl)-2-oxo-7-(1-pyridin-2-ylethylamino)quinoline-3-carbonitrile	1971458: Inhibition of PDE1C (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0190	uM
2-[4-[3-ethyl-4-[3-(naphthalen-2-ylmethyl)phenyl]phenyl]-3-propan-2-ylphenoxy]acetic acid	45096: Inhibition of calmodulin-dependent PDE(3’,5’-phosphodiesterase)	ic50	0.0200	uM
2-[2-ethoxy-5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonylphenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one	240757: Inhibition of phosphodiesterase 1	ic50	0.0200	uM
5-(1,3-benzodioxol-5-ylmethyl)-6-[[(1R)-1-(4-chlorophenyl)ethyl]amino]-1-propan-2-ylpyrazolo[5,4-d]pyrimidin-4-one	1652890: Inhibition of PDE1C2 (147 to 531 residues) (unknown origin) using [3H]-cGMP substrate incubated for 15 mins by liquid scintillation counting method	ic50	0.0200	uM
1-benzyl-4-cyclopentyl-2-oxo-7-(1-pyridin-2-ylethylamino)quinoline-3-carbonitrile	1971458: Inhibition of PDE1C (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0200	uM
cyclohexylmethyl 3-benzylsulfanylcarbonyl-4-[4-(difluoromethoxy)phenyl]-6-methyl-2-oxo-1,4-dihydropyrimidine-5-carboxylate	2070777: Inhibition of PDE1C2 (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0210	uM
1-benzyl-2-oxo-4-propan-2-yl-7-(1-pyridin-2-ylethylamino)quinoline-3-carbonitrile	1971458: Inhibition of PDE1C (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0220	uM
1-benzyl-4-(4-methylphenyl)-2-oxo-6-(1-pyridin-2-ylethylamino)quinoline-3-carbonitrile	1971458: Inhibition of PDE1C (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0240	uM
1-(cyclopentylmethyl)-4-(4-methylphenyl)-2-oxo-7-(1-pyridin-2-ylethylamino)quinoline-3-carbonitrile	1971458: Inhibition of PDE1C (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0250	uM
8-[(2-fluoro-4-methoxyphenyl)methyl]-13-(oxan-4-ylmethyl)-10-thia-3,5,6,8,13-pentazatetracyclo[7.7.0.02,6.011,16]hexadeca-1(9),2,4,11(16)-tetraen-7-one	1923539: Inhibition of PDE1 (unknown origin)	ic50	0.0260	uM
5-(1,3-benzodioxol-5-ylmethyl)-1-tert-butyl-6-[[(1R)-1-(4-chlorophenyl)ethyl]amino]pyrazolo[5,4-d]pyrimidin-4-one	1652890: Inhibition of PDE1C2 (147 to 531 residues) (unknown origin) using [3H]-cGMP substrate incubated for 15 mins by liquid scintillation counting method	ic50	0.0270	uM
3-cyclopentyl-5-[2-ethoxy-5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonylphenyl]-6H-[1,2]oxazolo[4,5-d]pyrimidin-7-one	240757: Inhibition of phosphodiesterase 1	ic50	0.0300	uM
8-cyclopentyl-2-[2-ethoxy-5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonylphenyl]-6-methyl-3H-imidazo[1,5-a][1,3,5]triazin-4-one	240757: Inhibition of phosphodiesterase 1	ic50	0.0300	uM
7-cyclopentyl-2-(2-ethoxyphenyl)-5-methyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one	240757: Inhibition of phosphodiesterase 1	ic50	0.0300	uM
3-O-(cyclohexylmethyl) 5-O-methyl 4-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-6-methyl-2-oxo-1,4-dihydropyrimidine-3,5-dicarboxylate	2070777: Inhibition of PDE1C2 (147 to 531 residues) (unknown origin) using 3H-cGMP as substrate incubated for 15 mins by liquid scintillation counter analysis	ic50	0.0370	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Cadmium	decreases expression, increases abundance	2
Doxorubicin	decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
Aflatoxin B1	decreases methylation	2
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	affects methylation, decreases methylation	1
didecyldimethylammonium	decreases expression	1
aflatoxin B2	affects methylation	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
PF-04254644	decreases activity	1
NSC 689534	increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	increases expression	1
Vorinostat	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Allergens	decreases expression, decreases abundance, decreases reaction, increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Vehicle Emissions	decreases abundance, decreases expression, decreases reaction, increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1

ChEMBL screening assays

185 unique, capped per target: 175 binding, 5 admet, 5 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1943756	Binding	Inhibition of recombinant human PDE1 using [3H]cAMP as substrate by scintillation proximity assay	The discovery of potent, selective, and orally active pyrazoloquinolines as PDE10A inhibitors for the treatment of Schizophrenia. — Bioorg Med Chem Lett
CHEMBL4348836	ADMET	Inhibition of PDE1 (unknown origin)	Structure Overhaul Affords a Potent Purine PI3Kδ Inhibitor with Improved Tolerability. — J Med Chem
CHEMBL655529	Functional	Inhibition of calmodulin-dependent PDE(3’,5’-phosphodiesterase)	Inhibition of protein-protein association by small molecules: approaches and progress. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0TH	ACTOne cAMP-PDE1C	Transformed 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