PDE1A

Summary

PDE1A (phosphodiesterase 1A, HGNC:8774) is a protein-coding gene on chromosome 2q32.1, encoding Dual specificity calcium/calmodulin-dependent 3’,5’-cyclic nucleotide phosphodiesterase 1A (P54750). Calcium/calmodulin-dependent cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cGMP and cAMP, which are key regulators of many important physiological processes.

Cyclic nucleotide phosphodiesterases (PDEs) play a role in signal transduction by regulating intracellular cyclic nucleotide concentrations through hydrolysis of cAMP and/or cGMP to their respective nucleoside 5-prime monophosphates. Members of the PDE1 family, such as PDE1A, are Ca(2+)/calmodulin (see CALM1; MIM 114180)-dependent PDEs (CaM-PDEs) that are activated by calmodulin in the presence of Ca(2+) (Michibata et al., 2001 [PubMed 11342109]; Fidock et al., 2002 [PubMed 11747989]).

Source: NCBI Gene 5136 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 107 total
• Druggable target: yes — 17 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001363871

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8774
Approved symbol	PDE1A
Name	phosphodiesterase 1A
Location	2q32.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000115252
Ensembl biotype	protein_coding
OMIM	171890
Entrez	5136

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 nonsense_mediated_decay

ENST00000351439, ENST00000358139, ENST00000409365, ENST00000410103, ENST00000435564, ENST00000462938, ENST00000482782, ENST00000495511, ENST00000858975, ENST00000858976, ENST00000961744, ENST00000961745, ENST00000961746, ENST00000961747

RefSeq mRNA: 18 — MANE Select: NM_001363871 NM_001003683, NM_001258312, NM_001258313, NM_001258314, NM_001363871, NM_001395258, NM_001395259, NM_001395260, NM_001395261, NM_001395262, NM_001395263, NM_001395264, NM_001395265, NM_001395266, NM_001395267, NM_001395268, NM_001395269, NM_005019

CCDS: CCDS2285, CCDS33344, CCDS58741, CCDS74612, CCDS86900

Canonical transcript exons

ENST00000409365 — 15 exons

Exon	Start	End
ENSE00000964528	182223864	182223964
ENSE00000964529	182205940	182206065
ENSE00000964530	182201688	182201789
ENSE00000964531	182201439	182201559
ENSE00000964532	182188979	182189060
ENSE00000964533	182186468	182186588
ENSE00000964534	182185892	182186079
ENSE00001371610	182147036	182147152
ENSE00003477441	182230006	182230146
ENSE00003576273	182231015	182231131
ENSE00003580261	182234432	182234498
ENSE00003661861	182240110	182240292
ENSE00003666528	182264301	182264414
ENSE00003964846	182426578	182427036
ENSE00003965422	182140041	182143038

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 98.36.

FANTOM5 (CAGE): breadth broad, TPM avg 7.3951 / max 803.8024, expressed in 636 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
32741	2.8639	500
32747	1.3865	140
32745	0.6852	116
32748	0.6293	105
32749	0.4188	85
32750	0.3788	79
32740	0.3112	127
32746	0.1959	58
32739	0.1956	102
32751	0.1182	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.36	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.95	gold quality
cortical plate	UBERON:0005343	96.60	gold quality
buccal mucosa cell	CL:0002336	96.06	gold quality
middle temporal gyrus	UBERON:0002771	96.03	gold quality
male germ cell	CL:0000015	95.79	gold quality
renal medulla	UBERON:0000362	95.64	gold quality
entorhinal cortex	UBERON:0002728	94.34	gold quality
parietal lobe	UBERON:0001872	92.68	gold quality
postcentral gyrus	UBERON:0002581	92.65	gold quality
superior frontal gyrus	UBERON:0002661	92.44	gold quality
cerebellar cortex	UBERON:0002129	91.12	gold quality
cerebellar hemisphere	UBERON:0002245	91.01	gold quality
endothelial cell	CL:0000115	90.93	gold quality
gall bladder	UBERON:0002110	90.92	gold quality
cerebellum	UBERON:0002037	90.59	gold quality
right coronary artery	UBERON:0001625	90.22	gold quality
cerebellar vermis	UBERON:0004720	90.17	gold quality
left coronary artery	UBERON:0001626	89.71	gold quality
prefrontal cortex	UBERON:0000451	89.54	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.49	gold quality
coronary artery	UBERON:0001621	89.17	gold quality
primary visual cortex	UBERON:0002436	88.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.92	gold quality
popliteal artery	UBERON:0002250	87.84	gold quality
tibial artery	UBERON:0007610	87.82	gold quality
calcaneal tendon	UBERON:0003701	87.55	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.51	gold quality
cerebral cortex	UBERON:0000956	87.41	gold quality
temporal lobe	UBERON:0001871	87.39	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	3638.70
E-GEOD-93593	yes	1810.34
E-HCAD-5	yes	70.67
E-CURD-135	no	363.52
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting PDE1A, 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-3064-3P	100.00	70.09	1254
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-299-3P	97.73	66.67	773
HSA-MIR-3674	97.01	68.86	1171
HSA-MIR-342-3P	96.44	67.48	1344
HSA-MIR-8088	89.27	73.01	56
HSA-MIR-4783-3P	73.56	61.87	82

Literature-anchored findings (GeneRIF, showing 11)

• PDE1A is permanently activated in human spermatozoa (PMID:12135876)
• Ca2+-calmodulin-dependent phosphodiesterase 1A is activated by sustained entry of Ca2+ (PMID:15272012)
• PDE1A is important in VSMC growth and survival and may contribute to the neointima formation in atherosclerosis and restenosis. (PMID:16514069)
• Variants in PDE1A are not associated with citalopram response in patient with depression. (PMID:18043711)
• PDE1A is unlikely to play an important role in antidepressant outcome in this sample (PMID:19214142)
• PDE1A is suggested to be involved in epigenetic mechanisms by targeting the epigenetic integrator UHRF1. (PMID:20807569)
• These results suggest that induction of PDE1A plays a critical role in cardiac fibroblast activation and cardiac fibrosis (PMID:22012077)
• Report significant associations of PDE1A single nucleotide polymorphisms with diastolic blood pressure and carotid intima-media thickness. (PMID:26464516)
• the p-substituted benzyl side chain at N2-position helps to enhance the PDE1 inhibitory profile. Depending on these observations, some new molecules are predicted that may possess better PDE1 inhibition (PMID:28132591)
• evidence that the rs182089527 mutation in PDE1A is involved in the development of nephrolithiasis and kidney cysts. (PMID:29262781)
• Identification of a Common Variant for Coronary Heart Disease at PDE1A Contributes to Individualized Treatment Goals and Risk Stratification of Cardiovascular Complications in Chinese Patients With Type 2 Diabetes. (PMID:37125963)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pde1a	ENSDARG00000060875
mus_musculus	Pde1a	ENSMUSG00000059173
rattus_norvegicus	Pde1a	ENSRNOG00000054212
caenorhabditis_elegans	pde-1	WBGENE00011433

Paralogs (20): PDE4A (ENSG00000065989), PDE8A (ENSG00000073417), PDE6C (ENSG00000095464), PDE4C (ENSG00000105650), PDE10A (ENSG00000112541), PDE8B (ENSG00000113231), PDE4D (ENSG00000113448), PDE1B (ENSG00000123360), PDE11A (ENSG00000128655), PDE6A (ENSG00000132915), PDE6B (ENSG00000133256), PDE5A (ENSG00000138735), PDE3B (ENSG00000152270), PDE1C (ENSG00000154678), 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 1A — P54750 (reviewed: P54750)

Alternative names: 61 kDa Cam-PDE, hCam-1

All UniProt accessions (2): A0A8Q3WKY5, P54750

UniProt curated annotations — full annotation on UniProt →

Function. Calcium/calmodulin-dependent cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cGMP and cAMP, which are key regulators of many important physiological processes. Has a higher efficiency with cGMP compared to cAMP.

Subunit / interactions. Homodimer. Interacts with YWHAZ.

Tissue specificity. Several tissues, including brain, kidney, testes and heart.

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 (9)

UniProt ID	Names	Canonical?
P54750-1	1, PDE1A3, PDE1A6	yes
P54750-2	2, PDE1A4, PDE1A5
P54750-3	3, PDE1A10
P54750-4	4, PDE1A5
P54750-5	5, PDE1A9
P54750-6	6, PDE1A1
P54750-7	7, PDE1A8
P54750-8	8, PDE1A11
P54750-9	9, PDE1A12

RefSeq proteins (18): NP_001003683, NP_001245241, NP_001245242, NP_001245243, NP_001350800, NP_001382187, NP_001382188, NP_001382189, NP_001382190, NP_001382191, NP_001382192, NP_001382193, NP_001382194, NP_001382195, NP_001382196, NP_001382197, NP_001382198, NP_005010 (=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 (14 total): binding site 5, splice variant 4, region of interest 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54750-F1	81.12	0.57

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): 219 (proton donor)

Ligand- & substrate-binding residues (5): 223; 259; 260; 260; 366

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-111957	Cam-PDE 1 activation
R-HSA-418457	cGMP effects
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 212 (showing top): GCANCTGNY_MYOD_Q6, TGACCTY_ERR1_Q2, TAL1ALPHAE47_01, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, CAGCTG_AP4_Q5, EFC_Q6, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, ATF1_Q6, RIGGI_EWING_SARCOMA_PROGENITOR_DN, WU_ALZHEIMER_DISEASE_DN, MODULE_99, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, CYTAGCAAY_UNKNOWN, DOUGLAS_BMI1_TARGETS_DN, KEGG_PURINE_METABOLISM

GO Biological Process (5): signal transduction (GO:0007165), regulation of smooth muscle cell apoptotic process (GO:0034391), cGMP catabolic process (GO:0046069), regulation of smooth muscle cell proliferation (GO:0048660), negative regulation of cAMP/PKA signal transduction (GO:0141162)

GO Molecular Function (10): 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), calmodulin-activated 3’,5’-cyclic-GMP phosphodiesterase activity (GO:0048101), 3’,5’-cyclic-nucleotide phosphodiesterase activity (GO:0004114), 3’,5’-cyclic-AMP phosphodiesterase activity (GO:0004115), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787), 3’,5’-cyclic-GMP phosphodiesterase activity (GO:0047555)

GO Cellular Component (2): cytosol (GO:0005829), neuronal cell body (GO:0043025)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Calmodulin induced events	1
Nitric oxide stimulates guanylate cyclase	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
3’,5’-cyclic-GMP phosphodiesterase activity	2
3’,5’-cyclic-nucleotide phosphodiesterase activity	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of muscle cell apoptotic process	1
smooth muscle cell apoptotic process	1
purine ribonucleotide catabolic process	1
cyclic nucleotide catabolic process	1
cGMP metabolic process	1
regulation of cell population proliferation	1
smooth muscle cell proliferation	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
binding	1
phosphoric ester hydrolase activity	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1
somatodendritic compartment	1
cell body	1

Protein interactions and networks

STRING

934 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE1A	ALDH7A1	P49419	884
PDE1A	CALM1	P02593	855
PDE1A	PARG	Q86W56	761
PDE1A	LHX6	Q9UPM6	722
PDE1A	CALML3	P27482	721
PDE1A	CALML5	Q9NZT1	721
PDE1A	CALML6	Q8TD86	701
PDE1A	CALML4	Q96GE6	701
PDE1A	AIFM1	O95831	589
PDE1A	MED6	O75586	582
PDE1A	MKI67	P46013	565
PDE1A	KIF4A	O95239	549
PDE1A	CCDC175	P0C221	505
PDE1A	CNN1	P51911	497
PDE1A	PARP1	P09874	491

IntAct

3 interactions, top by confidence:

A	B	Type	Score
YWHAZ	PDE1A	psi-mi:“MI:0915”(physical association)	0.400
PDE1C	PDE1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): PDE1A (Two-hybrid), PDE1A (Affinity Capture-MS), PDE1A (Proximity Label-MS), PDE1A (Affinity Capture-MS), CALM1 (Co-fractionation), PDE1A (Proximity Label-MS), PDE1A (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A4IF87, A4IJ06, A6H611, A9JRL3, E1C3P4, G1SPE9, O08593, O15228, O54735, O88910, P14100, P54750, P70453, P98192, Q01061, Q01064, Q01065, Q01066, Q01992, Q07832, Q13946, Q14123, Q28156, Q2KIX2, Q2TBA3, Q32NJ2, Q32NM1, Q4R678, Q4U2V3, Q61481, Q62673, Q641K1, Q64395, Q69ZK0, Q6NTL4, Q6ZMV9, Q7Z6J4, Q8CA95, Q8TCU6, Q96EN8

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
PDE1A	“down-regulates quantity”	“3’,5’-cyclic AMP”	“chemical modification”
3-isobutyl-1-methyl-7H-xanthine	“down-regulates activity”	PDE1A	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	5
Benign	32

Top pathogenic / likely-pathogenic (0)

SpliceAI

3638 predictions. Top by Δscore:

Variant	Effect	Δscore
2:182186094:C:CT	acceptor_gain	1.0000
2:182186462:TCATA:T	donor_loss	1.0000
2:182186463:CATA:C	donor_loss	1.0000
2:182186464:ATAC:A	donor_loss	1.0000
2:182186465:TA:T	donor_loss	1.0000
2:182186467:C:CA	donor_loss	1.0000
2:182186467:CCTG:C	donor_gain	1.0000
2:182186586:AACCT:A	acceptor_loss	1.0000
2:182186587:ACCTA:A	acceptor_loss	1.0000
2:182186588:CCTAC:C	acceptor_loss	1.0000
2:182186589:C:CG	acceptor_loss	1.0000
2:182186590:T:G	acceptor_loss	1.0000
2:182186599:C:CT	acceptor_gain	1.0000
2:182188981:A:AC	donor_gain	1.0000
2:182189057:CTCC:C	acceptor_gain	1.0000
2:182189058:TCC:T	acceptor_gain	1.0000
2:182189058:TCCC:T	acceptor_loss	1.0000
2:182189059:CC:C	acceptor_gain	1.0000
2:182189059:CCC:C	acceptor_gain	1.0000
2:182189059:CCCTG:C	acceptor_loss	1.0000
2:182189060:CC:C	acceptor_gain	1.0000
2:182189060:CCTG:C	acceptor_loss	1.0000
2:182189061:C:CC	acceptor_gain	1.0000
2:182231010:CTGA:C	donor_loss	1.0000
2:182231011:TGA:T	donor_loss	1.0000
2:182231012:GACCT:G	donor_loss	1.0000
2:182231013:AC:A	donor_loss	1.0000
2:182231014:C:CA	donor_loss	1.0000
2:182231039:T:C	donor_gain	1.0000
2:182231128:CATC:C	acceptor_gain	1.0000

AlphaMissense

3520 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:182186573:A:T	I424K	1.000
2:182186584:G:C	F420L	1.000
2:182186584:G:T	F420L	1.000
2:182186586:A:G	F420L	1.000
2:182201474:A:G	W380R	1.000
2:182201474:A:T	W380R	1.000
2:182201515:T:A	D366V	1.000
2:182201515:T:G	D366A	1.000
2:182201519:C:G	A365P	1.000
2:182201525:G:C	H363D	1.000
2:182201781:C:G	R320P	1.000
2:182201784:A:G	L319P	1.000
2:182206024:T:A	E289V	1.000
2:182206030:A:T	V287D	1.000
2:182206054:G:T	A279D	1.000
2:182223878:A:C	F270L	1.000
2:182223878:A:T	F270L	1.000
2:182223880:A:G	F270L	1.000
2:182223884:G:C	N268K	1.000
2:182223884:G:T	N268K	1.000
2:182223909:T:A	D260V	1.000
2:182223909:T:G	D260A	1.000
2:182230074:G:C	H219D	1.000
2:182240134:A:T	V125D	1.000
2:182240137:G:T	A124D	1.000
2:182240205:A:C	F101L	1.000
2:182240205:A:T	F101L	1.000
2:182240207:A:G	F101L	1.000
2:182240218:A:G	L97S	1.000
2:182240222:A:G	W96R	1.000

dbSNP variants (sampled 300 via entrez): RS1000006576 (2:182255401 T>C,G), RS1000009295 (2:182299020 T>C), RS1000014123 (2:182205254 T>A,C), RS1000014148 (2:182654979 T>C), RS1000019832 (2:182500101 C>T), RS1000021541 (2:182254660 AATG>A), RS1000023556 (2:182499826 C>G,T), RS1000024656 (2:182694856 T>G), RS1000036550 (2:182382517 C>T), RS1000038896 (2:182213677 G>A,T), RS1000051774 (2:182416136 T>C), RS1000054931 (2:182679332 C>T), RS1000056924 (2:182669946 C>T), RS1000066856 (2:182283249 C>T), RS1000067871 (2:182296968 C>G)

Disease associations

OMIM: gene MIM:171890 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST001204_17	Response to platinum-based chemotherapy (carboplatin)	9.000000e-06
GCST002813_14	Alzheimer’s disease in APOE e4+ carriers	2.000000e-06
GCST003542_73	Night sleep phenotypes	5.000000e-06
GCST004280_16	Diastolic blood pressure	2.000000e-08
GCST004947_1	Pulmonary arterial hypertension	8.000000e-09
GCST005316_170	Intelligence (MTAG)	2.000000e-08
GCST006166_99	Diastolic blood pressure x alcohol consumption interaction (2df test)	6.000000e-09
GCST006167_33	Mean arterial pressure x alcohol consumption interaction (2df test)	3.000000e-08
GCST007094_51	Diastolic blood pressure	7.000000e-15
GCST007269_78	Pulse pressure	4.000000e-08
GCST007704_33	Diastolic blood pressure	2.000000e-08
GCST007706_142	Mean arterial pressure	5.000000e-06
GCST008058_123	Estimated glomerular filtration rate	1.000000e-16
GCST008062_102	Blood urea nitrogen levels	5.000000e-06
GCST008747_148	Estimated glomerular filtration rate	5.000000e-07
GCST008971_111	Urate levels	4.000000e-06
GCST008972_251	Urate levels	3.000000e-09
GCST011365_79	Myocardial infarction	3.000000e-09
GCST011516_10	joint destruction in rheumatoid arthritis (rapid vs slow)	8.000000e-06
GCST90000025_832	Appendicular lean mass	3.000000e-19

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0007827	nighttime rest measurement
EFO:0006336	diastolic blood pressure
EFO:0004337	intelligence
EFO:0004329	alcohol drinking
EFO:0006340	mean arterial pressure
EFO:0005763	pulse pressure measurement
EFO:0004531	urate measurement
EFO:0005413	joint damage measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2095150 (PROTEIN FAMILY), CHEMBL2097161 (PROTEIN FAMILY), CHEMBL2363066 (PROTEIN FAMILY), CHEMBL3421 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

17 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 237,903 (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
CHEMBL484785	CRISABOROLE	4	1,482
CHEMBL19224	PAPAVERINE	3	22,172
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
CHEMBL4297290	TOVINONTRINE	2	126
CHEMBL4060569	TAK-915	1	14

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
Lu AF64196	Inhibition	7.24	pKi
SCH51866	Inhibition	7.2	pIC50
crisaborole	Inhibition	5.21	pIC50
vinpocetine	Inhibition	5.1	pIC50

Binding affinities (BindingDB)

198 measured of 200 human assays (200 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[(4-acetylphenyl)methyl]-5-(4-fluoro-3-methylanilino)-8,11,11-trimethyl-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2,5,9-trien-7-one	KI	0.1 nM	US-9073936: Organic compounds
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
4-[(4-acetylphenyl)methyl]-5-(4-fluoroanilino)-8,11,11-trimethyl-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2,5,9-trien-7-one	KI	0.2 nM	US-9073936: Organic compounds
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
4-[(4-acetylphenyl)methyl]-5-(3,4-difluoroanilino)-8,11,11-trimethyl-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2,5,9-trien-7-one	KI	0.3 nM	US-9073936: Organic compounds
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
1-[(2S)-butan-2-yl]-5-(2-ethoxy-3-pyridinyl)-3-methyl-N-[(5-methyl-1H-pyrazol-3-yl)methyl]pyrazolo[4,5-b]pyridin-7-amine	IC50	0.35 nM	US-11491140: 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-(4-fluoroanilino)-4-[[4-(1-hydroxyethyl)phenyl]methyl]-8,11,11-trimethyl-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2,5,9-trien-7-one	KI	0.5 nM	US-9073936: Organic compounds
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
1-[(2S)-butan-2-yl]-5-(2-ethoxy-3-pyridinyl)-3-methyl-N-(1H-pyrazol-5-ylmethyl)pyrazolo[4,5-b]pyridin-7-amine	IC50	4.6 nM	US-11491140: 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

ChEMBL bioactivities

2269 potent at pChembl≥5 of 2426 total, top 42 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	Ki	0.1	nM	CHEMBL3678507
10.00	IC50	0.1	nM	CHEMBL5081214
9.90	IC50	0.1259	nM	CHEMBL5080391
9.85	IC50	0.14	nM	CHEMBL5959210
9.85	IC50	0.14	nM	CHEMBL5843142
9.85	IC50	0.14	nM	CHEMBL5872664
9.80	IC50	0.1585	nM	CHEMBL5087564
9.70	Ki	0.2	nM	CHEMBL3678504
9.67	IC50	0.214	nM	CHEMBL6042932
9.60	IC50	0.2512	nM	CHEMBL5094110
9.59	IC50	0.26	nM	CHEMBL5912826
9.59	IC50	0.26	nM	CHEMBL5874788
9.59	IC50	0.26	nM	CHEMBL5977186
9.52	Ki	0.3	nM	CHEMBL3678506
9.50	IC50	0.3162	nM	CHEMBL5086895
9.50	IC50	0.3162	nM	CHEMBL5076558
9.46	IC50	0.35	nM	CHEMBL5990945
9.46	IC50	0.35	nM	CHEMBL5856741
9.46	IC50	0.343	nM	CHEMBL6057973
9.46	IC50	0.35	nM	CHEMBL6062258
9.44	IC50	0.366	nM	CHEMBL6005179
9.41	IC50	0.39	nM	CHEMBL6038988
9.41	IC50	0.39	nM	CHEMBL5943853
9.40	Ki	0.4	nM	CHEMBL3678507
9.39	IC50	0.41	nM	CHEMBL6024984
9.34	IC50	0.46	nM	CHEMBL5974031
9.33	IC50	0.47	nM	CHEMBL5800105
9.30	Ki	0.5	nM	CHEMBL3678505
9.14	IC50	0.73	nM	CHEMBL5785449
9.10	IC50	0.8	nM	CHEMBL5799714
9.10	IC50	0.79	nM	CHEMBL6064474
9.10	IC50	0.79	nM	CHEMBL5874494
9.10	IC50	0.79	nM	CHEMBL5866510
9.09	IC50	0.816	nM	CHEMBL5908735
9.02	IC50	0.96	nM	CHEMBL5843130
9.02	IC50	0.96	nM	CHEMBL5771846
9.00	Ki	1	nM	CHEMBL3678504
9.00	IC50	1	nM	CHEMBL5078680
9.00	IC50	1	nM	CHEMBL5088742
9.00	IC50	1	nM	CHEMBL5572993
9.00	IC50	1	nM	CHEMBL5961273
9.00	IC50	1	nM	CHEMBL6058241

PubChem BioAssay actives

203 with measured affinity, of 1023 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
[(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
1-(1-cyclopropylcyclopropyl)-5-(cyclopropylmethyl)-6,7,8,9-tetrahydro-[1,2,4]triazolo[4,3-a]quinoxalin-4-one	2096268: Inhibition of full-length recombinant human PDE1A using [3H]-cGMP as substrate incubated for 10 mins by SPA assay	ic50	0.0010	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
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
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
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
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
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
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-benzyl-5-phenyl-2H-pyrazolo[4,3-c][1,8]naphthyridin-4-one	2096296: Inhibition of PDE1A3 (unknown origin)	ic50	0.0320	uM
8-cyclopentyl-2-(2-ethoxyphenyl)-6-methyl-3H-imidazo[1,5-a][1,3,5]triazin-4-one	240757: Inhibition of phosphodiesterase 1	ic50	0.0400	uM
7,8-dimethoxy-N-[(2S)-1-(5-methyl-1H-pyrazol-3-yl)propan-2-yl]quinazolin-4-amine	1495730: Inhibition of full length recombinant human PDE1A using 3’,5’-[3H]cAMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0420	uM
6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]-N-[8-(hydroxyamino)-8-oxooctyl]pyridine-2-carboxamide	240893: Inhibitory concentration against Phosphodiesterase type 1	ic50	0.0430	uM
3-cyclopentyl-6-[2-ethoxy-5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonylphenyl]-7H-[1,2,4]triazolo[3,4-f][1,2,4]triazin-8-one	240757: Inhibition of phosphodiesterase 1	ic50	0.0500	uM
3-cyclopentyl-6-(2-ethoxyphenyl)-7H-[1,2,4]triazolo[3,4-f][1,2,4]triazin-8-one	240757: Inhibition of phosphodiesterase 1	ic50	0.0500	uM
5-[(3-chlorophenyl)methyl]-3-propan-2-yl-2,6-dihydropyrazolo[4,3-d]pyrimidin-7-one	352679: Inhibition of PDE1a	ic50	0.0540	uM
N-[(2S,3R)-2,3-dimethyloxolan-3-yl]-7,8-dimethoxy-N-methylquinazolin-4-amine	2124198: Inhibition of human recombinant GST-tagged PDE1A	ic50	0.0575	uM
4-ethoxy-N-(6-hydroxyhexyl)-3-(1-methyl-7-oxo-3-propyl-6H-pyrazolo[4,5-d]pyrimidin-5-yl)benzenesulfonamide	1194406: Inhibition of PDE1A1 (unknown origin) using fluorescently labeled cAMP substrate by fluorescence polarization assay	ic50	0.0620	uM
6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]-N-[4-[2-(hydroxyamino)-2-oxoethyl]-1,3-thiazol-2-yl]pyridine-2-carboxamide	240893: Inhibitory concentration against Phosphodiesterase type 1	ic50	0.0870	uM
7,8-dimethoxy-N-[1-(5-methyl-1H-pyrazol-3-yl)propan-2-yl]quinazolin-4-amine	1495730: Inhibition of full length recombinant human PDE1A using 3’,5’-[3H]cAMP as substrate after 30 mins by scintillation proximity assay	ic50	0.1180	uM
bis[(1R)-1-phenylethyl] 2,6-dimethyl-4-(1-methylindazol-5-yl)-1,4-dihydropyridine-3,5-dicarboxylate	1912035: Inhibition of PDE1A (142 to 552 residues) (unknown origin) expressed in Escherichia coli BL21 measured for 15 mins by liquid scintillation counter method	ic50	0.1450	uM
7,8-dimethoxy-N-pentan-3-ylquinazolin-4-amine	1924472: Inhibition of PDE1 (unknown origin)	ic50	0.1700	uM
1-[9-[4-[(E)-1-(4-iodophenyl)-2-phenylbut-1-enyl]phenoxy]nonyl]pyrrolidine	158738: Inhibitory activity against calmodulin-dependent Phosphodiesterase was reported.	ic50	0.2000	uM
1-[7-[4-[(E)-1-(4-iodophenyl)-2-phenylbut-1-enyl]phenoxy]heptyl]pyrrolidine	158738: Inhibitory activity against calmodulin-dependent Phosphodiesterase was reported.	ic50	0.2000	uM
2-(2-ethoxyphenyl)-6-methyl-8-propyl-3H-imidazo[1,5-a][1,3,5]triazin-4-one	240757: Inhibition of phosphodiesterase 1	ic50	0.2000	uM
3-cyclopentyl-5-(2-ethoxyphenyl)-6H-[1,2]oxazolo[4,5-d]pyrimidin-7-one	240757: Inhibition of phosphodiesterase 1	ic50	0.2000	uM
N-[4-[1-(hydroxyamino)-1-oxohexan-2-yl]-1,3-thiazol-2-yl]-6-(phenoxymethyl)pyridine-2-carboxamide	240893: Inhibitory concentration against Phosphodiesterase type 1	ic50	0.2000	uM
1-[8-[4-[(E)-1-(4-iodophenyl)-2-phenylbut-1-enyl]phenoxy]octyl]pyrrolidine	158738: Inhibitory activity against calmodulin-dependent Phosphodiesterase was reported.	ic50	0.2000	uM
Vardenafil	240957: Inhibition of human phosphodiesterase 1	ic50	0.2300	uM
Sildenafil	158761: Inhibitory activity against phosphodiesterase-1 (PDE1) isolated from canine lung	ic50	0.2700	uM
8-[4-[(E)-1-(4-iodophenyl)-2-phenylbut-1-enyl]phenoxy]-N,N-dimethyloctan-1-amine	158738: Inhibitory activity against calmodulin-dependent Phosphodiesterase was reported.	ic50	0.3000	uM
2-(2-ethoxyphenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one	240757: Inhibition of phosphodiesterase 1	ic50	0.3000	uM
2-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one	240757: Inhibition of phosphodiesterase 1	ic50	0.3000	uM
7-(2-hydroxy-3-naphthalen-2-yloxypropyl)-3-methyl-8-sulfanylidene-9H-purine-2,6-dione	261651: Inhibition of PDE1	ic50	0.3000	uM
8-chloro-5-(2H-tetrazol-5-ylmethoxy)spiro[1,3-dihydroquinazoline-4,1’-cyclohexane]-2-one	242214: Inhibition of human PDE1 expressed in baculovirus infected Sf9 cells	ic50	0.3200	uM
N-(2-pyrazin-2-yl-4,6-dihydrothieno[3,4-c]pyrazol-3-yl)naphthalene-1-carboxamide	1994821: Inhibition of PDE (unknown origin)	ic50	0.3300	uM
(1S,14R)-9-(4-ethoxybutoxy)-20,21,25-trimethoxy-15,30-dimethyl-7,23-dioxa-15,30-diazaheptacyclo[22.6.2.23,6.18,12.114,18.027,31.022,33]hexatriaconta-3(36),4,6(35),8,10,12(34),18,20,22(33),24,26,31-dodecaene	397126: Inhibition of calmodulin-dependent phosphodiesterase	ic50	0.3500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases expression, decreases methylation, affects cotreatment	3
Benzo(a)pyrene	increases expression, affects methylation, affects response to substance	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Nickel	decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Rotenone	affects expression, decreases expression	2
methylmercuric chloride	increases expression	1
methyleugenol	decreases expression	1
uranyl acetate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
ascorbate-2-phosphate	affects binding, affects cotreatment, increases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
entinostat	decreases expression	1
Chir 99021	affects cotreatment, increases expression, affects binding	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
XAV939	affects binding, affects cotreatment, increases expression	1
incobotulinumtoxinA	increases expression	1
PF-04254644	decreases activity	1
LDN 193189	increases expression, affects cotreatment	1
picoxystrobin	decreases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, increases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1

ChEMBL screening assays

215 unique, capped per target: 203 binding, 7 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

Clinical trials (associated diseases)

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