PDE1B

Summary

PDE1B (phosphodiesterase 1B, HGNC:8775) is a protein-coding gene on chromosome 12q13.2, encoding Dual specificity calcium/calmodulin-dependent 3’,5’-cyclic nucleotide phosphodiesterase 1B (Q01064). Cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.

The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE1 subfamily. Members of the PDE1 family are calmodulin-dependent PDEs that are stimulated by a calcium-calmodulin complex. This PDE has dual-specificity for the second messengers, cAMP and cGMP, with a preference for cGMP as a substrate. cAMP and cGMP function as key regulators of many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 5153 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 61 total
• Druggable target: yes — 16 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000924

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8775
Approved symbol	PDE1B
Name	phosphodiesterase 1B
Location	12q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000123360
Ensembl biotype	protein_coding
OMIM	171891
Entrez	5153

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000243052, ENST00000394277, ENST00000538346, ENST00000542335, ENST00000548855, ENST00000550285, ENST00000550620, ENST00000552774, ENST00000611899, ENST00000857306, ENST00000857307

RefSeq mRNA: 6 — MANE Select: NM_000924 NM_000924, NM_001165975, NM_001288768, NM_001288769, NM_001315534, NM_001315535

CCDS: CCDS53800, CCDS73477, CCDS8882

Canonical transcript exons

ENST00000243052 — 16 exons

Exon	Start	End
ENSE00001147267	54577860	54579239
ENSE00001183864	54549601	54549772
ENSE00003462886	54572601	54572741
ENSE00003495440	54575551	54575632
ENSE00003501318	54573608	54573709
ENSE00003503706	54577225	54577345
ENSE00003510263	54573355	54573480
ENSE00003532639	54549860	54549985
ENSE00003554492	54573148	54573248
ENSE00003557322	54569546	54569612
ENSE00003581672	54570241	54570357
ENSE00003592793	54576571	54576701
ENSE00003609726	54575992	54576100
ENSE00003665015	54575098	54575218
ENSE00003669636	54569184	54569366
ENSE00003671133	54566974	54567087

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 96.74.

FANTOM5 (CAGE): breadth broad, TPM avg 5.0999 / max 441.4255, expressed in 498 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125927	3.0853	261
125929	1.7538	330
125924	0.1447	67
125928	0.0474	34
125925	0.0453	30
125926	0.0234	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
caudate nucleus	UBERON:0001873	96.74	gold quality
nucleus accumbens	UBERON:0001882	95.72	gold quality
putamen	UBERON:0001874	95.43	gold quality
mucosa of stomach	UBERON:0001199	94.07	gold quality
right frontal lobe	UBERON:0002810	93.99	gold quality
prefrontal cortex	UBERON:0000451	91.34	gold quality
descending thoracic aorta	UBERON:0002345	91.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.29	gold quality
cingulate cortex	UBERON:0003027	89.92	gold quality
anterior cingulate cortex	UBERON:0009835	89.76	gold quality
thoracic aorta	UBERON:0001515	89.66	gold quality
ascending aorta	UBERON:0001496	89.62	gold quality
aorta	UBERON:0000947	88.66	gold quality
middle frontal gyrus	UBERON:0002702	88.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.49	gold quality
tibial artery	UBERON:0007610	88.22	gold quality
popliteal artery	UBERON:0002250	88.20	gold quality
frontal cortex	UBERON:0001870	87.96	gold quality
omental fat pad	UBERON:0010414	87.93	gold quality
peritoneum	UBERON:0002358	87.85	gold quality
neocortex	UBERON:0001950	87.31	gold quality
right ovary	UBERON:0002118	86.81	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.14	gold quality
telencephalon	UBERON:0001893	85.97	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.91	gold quality
left ovary	UBERON:0002119	85.50	gold quality
amygdala	UBERON:0001876	85.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.98	gold quality
left coronary artery	UBERON:0001626	84.57	gold quality
cerebral cortex	UBERON:0000956	83.83	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	5.21
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting PDE1B, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785

Literature-anchored findings (GeneRIF, showing 3)

• Selective up-regulation of PDE1B2 upon monocyte-to-macrophage differentiation. (PMID:15625104)
• PDE1B2 regulates a subset of phenotypic changes that occur upon phorbol-12-myristate-13-acetate-induced differentiation and likely also plays a role in differentiated macrophages by regulating agonist-stimulated cGMP levels (PMID:16407168)
• The c.1618G>A, p.Gly540Ser substitution in CNGA3 was identified as the causative mutation for a novel form of ACHM in Awassi sheep. Gene augmentation therapy restored vision in the affected sheep. This novel mutation provides a large-animal model that is valid for most human CNGA3 ACHM patients; the majority of them carry missense rather than premature-termination mutations. (PMID:28282490)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pde1b	ENSMUSG00000022489
rattus_norvegicus	Pde1b	ENSRNOG00000036828
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), 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 1B — Q01064 (reviewed: Q01064)

Alternative names: 63 kDa Cam-PDE

All UniProt accessions (4): A0A087WTW8, B4DK72, Q01064, F8VZK3

UniProt curated annotations — full annotation on UniProt →

Function. Cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a preference for cGMP as a substrate.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Cytosol.

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 (2)

UniProt ID	Names	Canonical?
Q01064-1	PDE1B1	yes
Q01064-2	PDE1B2

RefSeq proteins (6): NP_000915, NP_001159447, NP_001275697, NP_001275698, NP_001302463, NP_001302464 (=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 (49 total): helix 21, binding site 5, region of interest 5, turn 5, modified residue 4, splice variant 2, sequence conflict 2, chain 1, domain 1, strand 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
1TAZ	X-RAY DIFFRACTION	1.77
5UOY	X-RAY DIFFRACTION	1.82
4NPW	X-RAY DIFFRACTION	1.9
5B25	X-RAY DIFFRACTION	1.9
5W6E	X-RAY DIFFRACTION	1.9
5UP0	X-RAY DIFFRACTION	2.04
4NPV	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01064-F1	78.73	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): 223 (proton donor)

Ligand- & substrate-binding residues (5): 263; 264; 264; 370; 227

Post-translational modifications (4): 7, 15, 466, 514

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: 189 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_AMINE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_ASSOCIATIVE_LEARNING, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, MODULE_70, CEBPB_01, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (10): response to amphetamine (GO:0001975), signal transduction (GO:0007165), locomotory behavior (GO:0007626), visual learning (GO:0008542), monocyte differentiation (GO:0030224), cellular response to macrophage colony-stimulating factor stimulus (GO:0036006), dopamine catabolic process (GO:0042420), serotonin metabolic process (GO:0042428), cellular response to granulocyte macrophage colony-stimulating factor stimulus (GO:0097011), negative regulation of cAMP/PKA signal transduction (GO:0141162)

GO Molecular Function (11): 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), cyclic-nucleotide phosphodiesterase activity (GO:0004112), 3’,5’-cyclic-nucleotide phosphodiesterase activity (GO:0004114), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (3): cytosol (GO:0005829), neuronal cell body (GO:0043025), cytoplasm (GO:0005737)

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
cellular response to cytokine stimulus	2
3’,5’-cyclic-nucleotide phosphodiesterase activity	2
3’,5’-cyclic-GMP phosphodiesterase activity	2
cellular anatomical structure	2
response to amine	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
behavior	1
visual behavior	1
associative learning	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
response to macrophage colony-stimulating factor	1
dopamine metabolic process	1
catecholamine catabolic process	1
phenol-containing compound metabolic process	1
indole-containing compound metabolic process	1
response to granulocyte macrophage colony-stimulating factor	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
phosphoric diester hydrolase activity	1
cyclic-nucleotide phosphodiesterase activity	1
binding	1
phosphoric ester hydrolase activity	1
catalytic activity	1
cytoplasm	1
somatodendritic compartment	1
cell body	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

742 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE1B	ALDH7A1	P49419	852
PDE1B	MYL6B	P14649	785
PDE1B	CALM1	P02593	731
PDE1B	PPP1R1B	Q9UD71	721
PDE1B	CALML3	P27482	705
PDE1B	CALML5	Q9NZT1	705
PDE1B	CALML6	Q8TD86	683
PDE1B	CALML4	Q96GE6	683
PDE1B	SLC25A19	Q9HC21	674
PDE1B	PIP4K2C	Q8TBX8	639
PDE1B	ITGA7	Q13683	580
PDE1B	ADCY5	O95622	560
PDE1B	PDE2A	O00408	538
PDE1B	OR1Q1	Q15612	460
PDE1B	ADCY6	O43306	447

IntAct

5 interactions, top by confidence:

A	B	Type	Score
POT1	PDE1B	psi-mi:“MI:0915”(physical association)	0.510
PDE1B	UBE3A	psi-mi:“MI:0915”(physical association)	0.370
PDE1C	PDE1A	psi-mi:“MI:0914”(association)	0.350
PDE1B	POT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): PDE1B (Affinity Capture-MS), PDE1B (Affinity Capture-RNA), PDE1B (Affinity Capture-MS), PDE1B (Affinity Capture-RNA), PDE1B (Two-hybrid), PDE1B (Two-hybrid)

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

1 interactions.

A	Effect	B	Mechanism
3-isobutyl-1-methyl-7H-xanthine	“down-regulates activity”	PDE1B	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2719 predictions. Top by Δscore:

Variant	Effect	Δscore
12:54549981:TCTCT:T	donor_gain	1.0000
12:54549982:CTCTG:C	donor_loss	1.0000
12:54549983:TCTG:T	donor_loss	1.0000
12:54549984:CTGT:C	donor_loss	1.0000
12:54549985:TGTAA:T	donor_loss	1.0000
12:54549986:G:GG	donor_gain	1.0000
12:54549986:GTAA:G	donor_loss	1.0000
12:54551810:G:GT	donor_gain	1.0000
12:54566969:TGCA:T	acceptor_loss	1.0000
12:54566970:GCA:G	acceptor_loss	1.0000
12:54566972:A:AG	acceptor_gain	1.0000
12:54566972:AG:A	acceptor_gain	1.0000
12:54566972:AGGC:A	acceptor_loss	1.0000
12:54566972:AGGCT:A	acceptor_gain	1.0000
12:54566973:G:GA	acceptor_gain	1.0000
12:54566973:GG:G	acceptor_gain	1.0000
12:54566973:GGC:G	acceptor_gain	1.0000
12:54566973:GGCT:G	acceptor_gain	1.0000
12:54566973:GGCTG:G	acceptor_gain	1.0000
12:54567062:G:GT	donor_gain	1.0000
12:54569173:T:A	acceptor_gain	1.0000
12:54569174:G:A	acceptor_gain	1.0000
12:54569179:CTCAG:C	acceptor_loss	1.0000
12:54569181:CAGGC:C	acceptor_loss	1.0000
12:54569182:AGG:A	acceptor_loss	1.0000
12:54569183:GGCAA:G	acceptor_gain	1.0000
12:54569364:ACGG:A	donor_loss	1.0000
12:54569365:CGGTG:C	donor_loss	1.0000
12:54569366:GGTG:G	donor_loss	1.0000
12:54569367:G:GG	donor_gain	1.0000

AlphaMissense

3554 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:54569269:T:C	F105L	1.000
12:54569271:C:A	F105L	1.000
12:54569271:C:G	F105L	1.000
12:54569320:T:C	F122L	1.000
12:54569321:T:C	F122S	1.000
12:54569321:T:G	F122C	1.000
12:54569322:C:A	F122L	1.000
12:54569322:C:G	F122L	1.000
12:54569330:T:A	I125N	1.000
12:54569339:C:A	A128D	1.000
12:54572673:C:G	H223D	1.000
12:54573203:A:C	D264A	1.000
12:54573203:A:T	D264V	1.000
12:54573204:T:A	D264E	1.000
12:54573204:T:G	D264E	1.000
12:54573228:C:A	N272K	1.000
12:54573228:C:G	N272K	1.000
12:54573232:T:C	F274L	1.000
12:54573234:C:A	F274L	1.000
12:54573234:C:G	F274L	1.000
12:54573396:A:T	E293V	1.000
12:54573397:G:C	E293D	1.000
12:54573397:G:T	E293D	1.000
12:54573646:C:T	T334I	1.000
12:54573649:A:T	D335V	1.000
12:54575132:C:G	H367D	1.000
12:54575142:A:C	D370A	1.000
12:54575142:A:T	D370V	1.000
12:54575143:C:A	D370E	1.000
12:54575143:C:G	D370E	1.000

dbSNP variants (sampled 300 via entrez): RS1000041635 (12:54566279 A>T), RS1000079146 (12:54548572 T>A,C), RS1000112718 (12:54556907 T>C), RS1000213696 (12:54578918 T>A), RS1000273760 (12:54566838 A>G), RS1000299140 (12:54555151 T>A), RS1000543612 (12:54553295 C>T), RS1000557576 (12:54573406 C>T), RS1000867556 (12:54577951 A>G), RS1000904539 (12:54553592 C>G), RS1000974529 (12:54566088 C>T), RS1000978372 (12:54578294 G>C), RS1001208797 (12:54556416 A>C,G), RS1001270731 (12:54560452 T>C), RS1001324013 (12:54547782 TAAG>T)

Disease associations

OMIM: gene MIM:171891 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): cerebellar ataxia (MONDO:0000437)

Orphanet (1): Rare ataxia (Orphanet:102002)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003263_40	Post bronchodilator FEV1 in COPD	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2095150 (PROTEIN FAMILY), CHEMBL2097161 (PROTEIN FAMILY), CHEMBL2363066 (PROTEIN FAMILY), CHEMBL4425 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

16 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 203,846 (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
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
CHEMBL2180408	JNJ-42396302	1	12
CHEMBL3770459	LENRISPODUN PHOSPHATE	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 (3 total), top 3:

Ligand	Action	Affinity	Parameter
lenrispodun	Inhibition	10.24	pIC50
Lu AF64196	Inhibition	7.86	pKi
SCH51866	Inhibition	7.2	pIC50

Binding affinities (BindingDB)

915 measured of 1240 human assays (1240 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
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
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

ChEMBL bioactivities

2669 potent at pChembl≥5 of 2791 total, top 28 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.38	IC50	0.042	nM	CHEMBL5990945
10.38	IC50	0.042	nM	CHEMBL5856741
10.38	IC50	0.042	nM	CHEMBL6062258
10.35	IC50	0.045	nM	CHEMBL5959210
10.35	IC50	0.045	nM	CHEMBL5843142
10.35	IC50	0.045	nM	CHEMBL5872664
10.24	IC50	0.058	nM	LENRISPODUN PHOSPHATE
10.19	IC50	0.065	nM	CHEMBL6025583
10.16	IC50	0.069	nM	CHEMBL5943853
10.15	IC50	0.071	nM	CHEMBL5974031
10.02	IC50	0.095	nM	CHEMBL5888078
10.02	IC50	0.095	nM	CHEMBL6024984
10.02	IC50	0.095	nM	CHEMBL5934813
10.00	IC50	0.1	nM	CHEMBL5081214
10.00	IC50	0.1	nM	CHEMBL5912826
10.00	IC50	0.1	nM	CHEMBL5874788
9.96	IC50	0.11	nM	CHEMBL5799714
9.96	IC50	0.11	nM	CHEMBL5740051
9.92	IC50	0.12	nM	CHEMBL5843130
9.92	IC50	0.12	nM	CHEMBL5771846
9.90	IC50	0.1259	nM	CHEMBL5080391
9.85	IC50	0.14	nM	CHEMBL5784357
9.85	IC50	0.14	nM	CHEMBL6064474
9.85	IC50	0.14	nM	CHEMBL5874494
9.85	IC50	0.14	nM	CHEMBL5866510
9.82	IC50	0.15	nM	CHEMBL5995185
9.82	IC50	0.15	nM	CHEMBL5774816
9.82	IC50	0.15	nM	CHEMBL6003959

PubChem BioAssay actives

255 with measured affinity, of 949 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
(11R,15S)-5-anilino-4-[[4-(6-fluoro-2-pyridinyl)phenyl]methyl]-8-methyl-1,3,4,8,10-pentazatetracyclo[7.6.0.02,6.011,15]pentadeca-2,5,9-trien-7-one;phosphoric acid	1443962: Inhibition of PDE1B (unknown origin)	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
1-(1-cyclopropylcyclopropyl)-5-(cyclopropylmethyl)-6,7,8,9-tetrahydro-[1,2,4]triazolo[4,3-a]quinoxalin-4-one	2096269: Inhibition of PDE1B (unknown origin) using [3H]-cGMP substrate incubated for 15 mins by liquid scintillation counting method	ic50	0.0004	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
1-tert-butyl-6-[[(1R)-1-(4-chlorophenyl)ethyl]amino]-5-[(4-fluorophenyl)methyl]pyrazolo[5,4-d]pyrimidin-4-one	1652891: Inhibition of PDE1B (146 to 506 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	1443924: Inhibition of full length GST-tagged PDE1B (unknown origin) assessed as decrease in FAM-cAMP hydrolysis preincubated for 5 mins followed by FAM-cAMP addition measured after 30 mins by IMAP assay	ic50	0.0030	uM
3-anilino-7-(cyclopropylmethyl)-2-[[4-(6-fluoro-2-pyridinyl)phenyl]methyl]-5-methylpyrazolo[3,4-d]pyrimidine-4,6-dione	2096269: Inhibition of PDE1B (unknown origin) using [3H]-cGMP substrate incubated for 15 mins by liquid scintillation counting method	ic50	0.0038	uM
4-[(1S)-6-chloro-2,3-dihydro-1H-inden-1-yl]-7,8-dimethoxyquinazoline	1495731: Inhibition of full length recombinant human PDE1B1 using 3’,5’-[3H]cAMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0045	uM
2-[4-(methoxymethyl)cyclohexyl]oxy-3-methyl-7-(oxan-4-yl)imidazo[5,1-f][1,2,4]triazin-4-one	2124200: Inhibition of PDE1B (unknown origin)	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
7,8-dimethoxy-N-[(2S)-1-(5-methyl-1H-pyrazol-3-yl)propan-2-yl]quinazolin-4-amine	1923581: Inhibition of recombinant full length PDE1B in human myocardium using cAMP as substrate	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
13-(2,2-difluorocyclopropanecarbonyl)-8-[(4-methoxyphenyl)methyl]-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	1443924: Inhibition of full length GST-tagged PDE1B (unknown origin) assessed as decrease in FAM-cAMP hydrolysis preincubated for 5 mins followed by FAM-cAMP addition measured after 30 mins by IMAP assay	ic50	0.0110	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
N-[(2S,3R)-2,3-dimethyloxolan-3-yl]-7,8-dimethoxy-N-methylquinazolin-4-amine	2124200: Inhibition of PDE1B (unknown origin)	ic50	0.0138	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
7-(cyclopropylmethyl)-3-(4-fluoroanilino)-5-methyl-2-[(4-methylsulfonylphenyl)methyl]pyrazolo[3,4-d]pyrimidine-4,6-dione	2096269: Inhibition of PDE1B (unknown origin) using [3H]-cGMP substrate incubated for 15 mins by liquid scintillation counting method	ic50	0.0210	uM
7,8-dimethoxy-N-[1-(5-methyl-1H-pyrazol-3-yl)propan-2-yl]quinazolin-4-amine	1495731: Inhibition of full length recombinant human PDE1B1 using 3’,5’-[3H]cAMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0210	uM
5-benzyl-6-[[(1R)-1-(4-chlorophenyl)ethyl]amino]-1-cyclopentylpyrazolo[5,4-d]pyrimidin-4-one	1652891: Inhibition of PDE1B (146 to 506 residues) (unknown origin) using [3H]-cGMP substrate incubated for 15 mins by liquid scintillation counting method	ic50	0.0230	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	1443924: Inhibition of full length GST-tagged PDE1B (unknown origin) assessed as decrease in FAM-cAMP hydrolysis preincubated for 5 mins followed by FAM-cAMP addition measured after 30 mins by IMAP assay	ic50	0.0260	uM
6,7,8-trimethoxy-N-[1-(5-methyl-1H-pyrazol-3-yl)propan-2-yl]quinazolin-4-amine	1495731: Inhibition of full length recombinant human PDE1B1 using 3’,5’-[3H]cAMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0270	uM
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	1443924: Inhibition of full length GST-tagged PDE1B (unknown origin) assessed as decrease in FAM-cAMP hydrolysis preincubated for 5 mins followed by FAM-cAMP addition measured after 30 mins by IMAP assay	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
8-[(4-chloro-2-fluorophenyl)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	1443924: Inhibition of full length GST-tagged PDE1B (unknown origin) assessed as decrease in FAM-cAMP hydrolysis preincubated for 5 mins followed by FAM-cAMP addition measured after 30 mins by IMAP assay	ic50	0.0310	uM
6,7,8-trimethoxy-N-pentan-3-ylquinazolin-4-amine	1495731: Inhibition of full length recombinant human PDE1B1 using 3’,5’-[3H]cAMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0350	uM
5-[(3-chlorophenyl)methyl]-3-propan-2-yl-2,6-dihydropyrazolo[4,3-d]pyrimidin-7-one	352680: Inhibition of PDE1b	ic50	0.0380	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
8-[(4-chlorophenyl)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	1443924: Inhibition of full length GST-tagged PDE1B (unknown origin) assessed as decrease in FAM-cAMP hydrolysis preincubated for 5 mins followed by FAM-cAMP addition measured after 30 mins by IMAP assay	ic50	0.0410	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-methyl-7-(oxan-4-yl)-2-[[4-(trifluoromethyl)cyclohexyl]methoxy]imidazo[5,1-f][1,2,4]triazin-4-one	2124200: Inhibition of PDE1B (unknown origin)	ic50	0.0439	uM
3-benzyl-5-methyl-2-[(4-phenylphenyl)methyl]spiro[8H-imidazo[2,1-b]purine-7,1’-cyclopentane]-4-one	1443924: Inhibition of full length GST-tagged PDE1B (unknown origin) assessed as decrease in FAM-cAMP hydrolysis preincubated for 5 mins followed by FAM-cAMP addition measured after 30 mins by IMAP assay	ic50	0.0480	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
1-(2-chlorophenyl)-6-[(2R)-3,3,3-trifluoro-2-methylpropyl]-5H-pyrazolo[5,4-d]pyrimidin-4-one	1587244: Inhibition of PDE1B catalytic domain (10 to 487 residues) (unknown origin) using 3H-cGMP as substrate after 15 mins by liquid scintillation counting method	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
6,7-dimethoxy-N-[1-(5-methyl-1H-pyrazol-3-yl)propan-2-yl]quinazolin-4-amine	1495731: Inhibition of full length recombinant human PDE1B1 using 3’,5’-[3H]cAMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0520	uM
8-[(4-chlorophenyl)methyl]-13-(cyclopropanecarbonyl)-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	1443924: Inhibition of full length GST-tagged PDE1B (unknown origin) assessed as decrease in FAM-cAMP hydrolysis preincubated for 5 mins followed by FAM-cAMP addition measured after 30 mins by IMAP assay	ic50	0.0530	uM
6-[[(1R)-1-(4-chlorophenyl)ethyl]amino]-1-cyclopentyl-5H-pyrazolo[5,4-d]pyrimidin-4-one	1652891: Inhibition of PDE1B (146 to 506 residues) (unknown origin) using [3H]-cGMP substrate incubated for 15 mins by liquid scintillation counting method	ic50	0.0800	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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	affects methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
M-VAC protocol	increases response to substance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
pinostrobin	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Cytarabine	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Lipopolysaccharides	decreases expression, affects cotreatment	1
Menthol	decreases expression	1
Phthalic Acids	decreases methylation	1
Tretinoin	increases expression	1
Triclosan	increases expression	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	decreases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

192 unique, capped per target: 180 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

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0TG	ACTOne cAMP-PDE1B	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT04107740	PHASE4	COMPLETED	C-Trelin Orally Disintegrated(OD) Tablet 5mg in Ataxia Due to Spinocerebellar Degeneration
NCT01970098	PHASE3	COMPLETED	A Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970111	PHASE3	COMPLETED	An Extension Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970124	PHASE3	COMPLETED	A Long-Term Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970137	PHASE3	COMPLETED	A 24-week Open-label Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT02889302	PHASE3	COMPLETED	An Additional Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT03408080	PHASE3	ACTIVE_NOT_RECRUITING	Open Pilot Trial of BHV-4157
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT03901638	PHASE3	TERMINATED	Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
NCT07040137	PHASE3	RECRUITING	Confirmatory Study 3 of KPS-0373 in Patients With Spinocerebellar Degeneration
NCT00034242	PHASE2	COMPLETED	High-Dose Intravenous Immunoglobulin to Treat Cerebellar Degeneration
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00863538	PHASE2	COMPLETED	Phase II Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01004016	PHASE2	COMPLETED	A Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01350440	PHASE2	COMPLETED	Safety and Efficacy of Intravenous Immune Globulin in Treating Spinocerebellar Ataxia
NCT02540655	PHASE2	COMPLETED	Efficacy and Safety Study of Stemchymal® in Polyglutamine Spinocerebellar Ataxia
NCT03932669	PHASE2	COMPLETED	Effect of Nilotinib in Cerebellar Ataxia Patients
NCT04301284	PHASE2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT05125666	PHASE2	UNKNOWN	Efficacy of Dual Task Training on Children With Ataxia After Medulloblastoma Resection
NCT06397274	PHASE2	NOT_YET_RECRUITING	Stemchymal® for Polyglutamine Spinocerebellar Ataxia
NCT00683943	PHASE1	COMPLETED	Lithium Treatment for Patients With Spinocerebellar Ataxia Type I
NCT02287064	PHASE1	UNKNOWN	An Open-label Trial of Intravenous Immune Globulin (IVIG)in Treating Spinocerebellar Ataxias
NCT05157802	PHASE1	ACTIVE_NOT_RECRUITING	Promoting Physical Activity Engagement for People With Early-stage Cerebellar Ataxia
NCT01104649	PHASE2/PHASE3	COMPLETED	Efficacy of Riluzole in Hereditary Cerebellar Ataxia
NCT02960893	PHASE2/PHASE3	COMPLETED	Trial in Adult Participants With Spinocerebellar Ataxia (SCA)
NCT00244361	PHASE1/PHASE2	COMPLETED	Effectiveness of Rituximab in Pediatric OMS Patients.
NCT01649687	PHASE1/PHASE2	COMPLETED	Treatment of Cerebellar Ataxia With Mesenchymal Stem Cells
NCT01958177	PHASE1/PHASE2	UNKNOWN	Clinical Study to Evaluate the Safety and Efficacy BMMNC in Cerebellar Ataxia
NCT02829268	PHASE1/PHASE2	COMPLETED	A Clinical Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome
NCT00001324	Not specified	COMPLETED	PET Scan to Study Brain Control of Human Movement
NCT00006492	Not specified	COMPLETED	Gluten-Free Diet in Patients With Gluten Sensitivity and Cerebellar Ataxia
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00272272	Not specified	COMPLETED	Fall Prevention in a Geriatric Nursing Home Setting Using the Music of Nolwenn Leroy
NCT00654251	Not specified	COMPLETED	Measuring Neurological Impairment and Functional Visual Assessment In Spinocerebellar Ataxias
NCT00692861	Not specified	COMPLETED	Autoimmunity in Neurologic Complications of Celiac Disease
NCT01037777	Not specified	COMPLETED	RISCA : Prospective Study of Individuals at Risk for SCA1, SCA2, SCA3, SCA6, SCA7
NCT01307176	Not specified	COMPLETED	Exercise Training Program for Cerebellar Ataxia
NCT01428531	Not specified	COMPLETED	Special Drug Use Investigation for Arixtra® (Fondaparinux) Venous Thromboembolism Treatment