PDE9A

Summary

PDE9A (phosphodiesterase 9A, HGNC:8795) is a protein-coding gene on chromosome 21q22.3, encoding High affinity cGMP-specific 3’,5’-cyclic phosphodiesterase 9A (O76083). Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes.

The protein encoded by this gene catalyzes the hydrolysis of cAMP and cGMP to their corresponding monophosphates. The encoded protein plays a role in signal transduction by regulating the intracellular concentration of these cyclic nucleotides. Multiple transcript variants encoding several different isoforms have been found for this gene.

Source: NCBI Gene 5152 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 115 total
• Druggable target: yes — 9 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002606

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8795
Approved symbol	PDE9A
Name	phosphodiesterase 9A
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000160191
Ensembl biotype	protein_coding
OMIM	602973
Entrez	5152

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 32 protein_coding, 14 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000291539, ENST00000328862, ENST00000335440, ENST00000335512, ENST00000349112, ENST00000380328, ENST00000398224, ENST00000398225, ENST00000398227, ENST00000398229, ENST00000398232, ENST00000398234, ENST00000398236, ENST00000460905, ENST00000460989, ENST00000462571, ENST00000466472, ENST00000467162, ENST00000467403, ENST00000468805, ENST00000470987, ENST00000472401, ENST00000486902, ENST00000489319, ENST00000490803, ENST00000495343, ENST00000495521, ENST00000497805, ENST00000890115, ENST00000890116, ENST00000890117, ENST00000890118, ENST00000890119, ENST00000890120, ENST00000890121, ENST00000890122, ENST00000890123, ENST00000890124, ENST00000890125, ENST00000936961, ENST00000936962, ENST00000936963, ENST00000936964, ENST00000936965, ENST00000936966, ENST00000936967, ENST00000936968

RefSeq mRNA: 21 — MANE Select: NM_002606 NM_001001567, NM_001001568, NM_001001569, NM_001001570, NM_001001571, NM_001001572, NM_001001573, NM_001001574, NM_001001575, NM_001001576, NM_001001577, NM_001001578, NM_001001579, NM_001001580, NM_001001581, NM_001001582, NM_001001583, NM_001001584, NM_001001585, NM_001315533, NM_002606

CCDS: CCDS13690, CCDS33567, CCDS33568, CCDS33569, CCDS33570, CCDS33571, CCDS42941, CCDS42942, CCDS42943, CCDS42944, CCDS42945, CCDS42946, CCDS42947

Canonical transcript exons

ENST00000291539 — 20 exons

Exon	Start	End
ENSE00003461715	42769027	42769155
ENSE00003490275	42770703	42770798
ENSE00003492285	42732070	42732124
ENSE00003538925	42758999	42759085
ENSE00003546441	42760825	42760907
ENSE00003561153	42765381	42765494
ENSE00003565257	42687917	42687994
ENSE00003586792	42762083	42762239
ENSE00003602236	42760328	42760432
ENSE00003611375	42768188	42768292
ENSE00003625815	42686192	42686262
ENSE00003642531	42753990	42754064
ENSE00003643013	42775280	42775509
ENSE00003645170	42751116	42751197
ENSE00003656908	42733356	42733426
ENSE00003667734	42743776	42743860
ENSE00003681162	42653621	42653883
ENSE00003689265	42698968	42699011
ENSE00003691085	42731770	42731949
ENSE00003692648	42772439	42772520

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 97.72.

FANTOM5 (CAGE): breadth broad, TPM avg 4.8100 / max 109.5979, expressed in 878 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189320	3.4602	850
189321	1.1581	378
189322	0.0892	36
189331	0.0593	12
189332	0.0292	8
189330	0.0125	4
189329	0.0015	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	97.72	gold quality
transverse colon	UBERON:0001157	96.81	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.70	gold quality
ganglionic eminence	UBERON:0004023	96.29	gold quality
ventricular zone	UBERON:0003053	95.97	gold quality
oocyte	CL:0000023	95.47	gold quality
sural nerve	UBERON:0015488	95.02	gold quality
sigmoid colon	UBERON:0001159	94.70	gold quality
colon	UBERON:0001155	94.50	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.40	gold quality
large intestine	UBERON:0000059	94.21	gold quality
cortical plate	UBERON:0005343	92.99	gold quality
intestine	UBERON:0000160	92.88	gold quality
nerve	UBERON:0001021	91.75	gold quality
tibial nerve	UBERON:0001323	91.75	gold quality
prostate gland	UBERON:0002367	91.75	gold quality
rectum	UBERON:0001052	91.56	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.93	gold quality
lower esophagus	UBERON:0013473	90.85	gold quality
cranial nerve II	UBERON:0000941	90.51	gold quality
secondary oocyte	CL:0000655	90.45	gold quality
putamen	UBERON:0001874	90.12	gold quality
small intestine	UBERON:0002108	89.87	gold quality
renal medulla	UBERON:0000362	88.50	gold quality
caudate nucleus	UBERON:0001873	88.36	gold quality
embryo	UBERON:0000922	87.83	gold quality
colonic epithelium	UBERON:0000397	87.76	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.49	gold quality
metanephros cortex	UBERON:0010533	87.47	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.37	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA2, GLI1

miRNA regulators (miRDB)

17 targeting PDE9A, 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-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3686	99.90	70.53	2432
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-5094	98.63	67.11	1062
HSA-MIR-218-2-3P	98.08	67.21	601
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-217-3P	95.67	68.42	1000

Literature-anchored findings (GeneRIF, showing 11)

• Identification and distribution of different variants produced by differential splicing of phosphodiesterase 9A mRNA. (PMID:12565835)
• X ray crystallography with IBMX inhibitor binding (PMID:15210993)
• The data suggests the utilization of two different start codons to produce a variety of different PDE9A proteins, allowing specific subcellular location of PDE9A splice variants. (PMID:17090334)
• PDE9A, is unlikely to play an important role in antidepressant outcome in this sample (PMID:19214142)
• Data show that PDE9A inhibitor, BAY-73-6691, significantly reduced basal and sickle cell (SCA) neutrophil adhesion; this was accompanied by decreased SCA neutrophil surface expressions of the L-selectin and CD11b adhesion molecules. (PMID:21336703)
• PDE9 is widely distributed in the urothelial epithelium of the human lower urinary tract and its potential roles may be different from those of PDE5. (PMID:21736695)
• In vivo effects of PDE9A inhibition included reversal of the respective disruptions of working memory. (PMID:22328573)
• it is concluded that assessment of PDE5 and PDE9 expression may be useful in the differential diagnosis of benign and malignant breast disease and successful treatment of breast cancer (PMID:22960860)
• PDE9A can regulate cGMP signalling independent of the nitric oxide pathway, and its role in stress-induced heart disease suggests potential as a therapeutic target. (PMID:25799991)
• Evaluation of phosphodiesterase 9A as a novel biomarker in heart failure with preserved ejection fraction. (PMID:33787083)
• Prognostic and clinicopathological insights of phosphodiesterase 9A gene as novel biomarker in human colorectal cancer. (PMID:34016083)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pde9aa	ENSDARG00000060280
mus_musculus	Pde9a	ENSMUSG00000041119
rattus_norvegicus	Pde9a	ENSRNOG00000001174

Paralogs (20): PDE4A (ENSG00000065989), PDE8A (ENSG00000073417), PDE6C (ENSG00000095464), PDE4C (ENSG00000105650), PDE10A (ENSG00000112541), PDE8B (ENSG00000113231), PDE4D (ENSG00000113448), PDE1A (ENSG00000115252), PDE1B (ENSG00000123360), PDE11A (ENSG00000128655), PDE6A (ENSG00000132915), PDE6B (ENSG00000133256), PDE5A (ENSG00000138735), PDE3B (ENSG00000152270), PDE1C (ENSG00000154678), PDE7B (ENSG00000171408), PDE3A (ENSG00000172572), PDE4B (ENSG00000184588), PDE2A (ENSG00000186642), PDE7A (ENSG00000205268)

Protein

Protein identifiers

High affinity cGMP-specific 3’,5’-cyclic phosphodiesterase 9A — O76083 (reviewed: O76083)

All UniProt accessions (4): O76083, A0A0S2Z475, A0A0S2Z4A3, A0A0S2Z4T6

UniProt curated annotations — full annotation on UniProt →

Function. Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes. Highly specific: compared to other members of the cyclic nucleotide phosphodiesterase family, has the highest affinity and selectivity for cGMP. Specifically regulates natriuretic-peptide-dependent cGMP signaling in heart, acting as a regulator of cardiac hypertrophy in myocytes and muscle. Does not regulate nitric oxide-dependent cGMP in heart. Additional experiments are required to confirm whether its ability to hydrolyze natriuretic-peptide-dependent cGMP is specific to heart or is a general feature of the protein. In brain, involved in cognitive function, such as learning and long-term memory.

Subunit / interactions. Homodimer.

Subcellular location. Cell projection. Ruffle membrane. Cytoplasm. Perinuclear region. Golgi apparatus. Endoplasmic reticulum. Cell membrane. Sarcolemma Cell projection. Perinuclear region Cytoplasm. Endoplasmic reticulum Cytoplasm.

Tissue specificity. Expressed in all tissues examined (testis, brain, small intestine, skeletal muscle, heart, lung, thymus, spleen, placenta, kidney, liver, pancreas, ovary and prostate) except blood. Highest levels in brain, heart, kidney, spleen, prostate and colon. Isoform PDE9A12 is found in prostate. In brain, present in the cortex, cerebellum, and subiculum (at protein level). In heart, primarily localizes to myocytes.

Activity regulation. Inhibited by zaprinast; inhibitor is however not specific to PDE9A. Specifically inhibited by BAY-73-6691 (1-(2-chlorophenyl)-6-((2R)-3,3,3- trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo(3,4-d)pyrimidine-4-one). BAY-73-9961 has two enantiomers, (R) and (S), due to the presence of a chiral center, and both forms vary in their pattern of interaction. Specifically inhibited by PF-4181366 (4H-Pyrazolo[3,4-d]pyrimidin-4-one, 1- cyclopentyl-1,5-dihydro-6-[(3S,4S)-4-methyl- 1-(6-quinoxalinylmethyl)-3-pyrrolidinyl]-one). Specifically inhibited by PF-4449613 ((R)-6-(1-(3-phenoxyazetidin-1-yl)ethyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin- 4(5H)-one). Specifically inhibited by inhibitor 28 (2-((1-(2-Chlorophenyl)-4-hydroxy-1Hpyrazolo[ 3,4-d]pyrimidin-6-yl)amino)-N-(4- methoxyphenyl)propanamide): inhibitor forms a hydrogen bond with Tyr-484 and Gln-513. Specifically inhibited by 1-Cyclopentyl-6-[(1r)-1-(3-phenoxyazetidin- 1-Yl)ethyl]-1,5-dihydro-4h-pyrazolo[3,4-D] pyrimidin-4-one: inhibitor forms a hydrogen bond with Tyr-484 and Gln-513.

Cofactor. Binds 1 Zn(2+) ion per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Tightly binds zinc. Binds 1 Mg(2+) ions per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Binds magnesium less tightly than zinc.

Induction. Up-regulated in left ventricular hypertrophy from aortic stenosis and following heart failure with preserved ejection fraction (at protein level).

Pathway. Purine metabolism; 3’,5’-cyclic GMP degradation; GMP from 3’,5’-cyclic GMP: step 1/1.

Miscellaneous. PDE9A is a potential target for treatment of diseases such as stress-induced heart disease or long-term memory defects. Specific inhibitors, such as BAY-73-6691 or PF-4449613 are promising candidates for clinical tests. N-(4-methoxyphenyl)-N2-[1-(2-methylphenyl)-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-L-alaninamide correspond to compound 28.

Similarity. Belongs to the cyclic nucleotide phosphodiesterase family. PDE9 subfamily.

Isoforms (16)

UniProt ID	Names	Canonical?
O76083-1	PDE9A1	yes
O76083-2	PDE9A2
O76083-3	PDE9A3
O76083-4	PDE9A4
O76083-5	PDE9A5
O76083-6	PDE9A6, PDE9A5
O76083-7	PDE9A7, PDE9A8, PDE9A14, PDE9A19, PDE9A20
O76083-8	PDE9A9
O76083-9	PDE9A10
O76083-10	PDE9A11, PDE9A15
O76083-11	PDE9A12
O76083-12	PDE9A13
O76083-13	PDE9A16
O76083-14	PDE9A17
O76083-15	PDE9A18
O76083-16	PDE9A21

RefSeq proteins (21): NP_001001567, NP_001001568, NP_001001569, NP_001001570, NP_001001571, NP_001001572, NP_001001573, NP_001001574, NP_001001575, NP_001001576, NP_001001577, NP_001001578, NP_001001579, NP_001001580, NP_001001581, NP_001001582, NP_001001583, NP_001001584, NP_001001585, NP_001302462, NP_002597* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00233

Enzyme classification (BRENDA):

• EC 3.1.4.35 — 3’,5’-cyclic-GMP phosphodiesterase (BRENDA: 27 organisms, 45 substrates, 302 inhibitors, 50 Km, 11 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CGMP	0.0002–1.6	25
3’,5’-CGMP	0.0003–1	16
3’,5’-CAMP	0.001–0.82	5
2’-O-ANTHRANILOYL-CGMP	0.0247–0.0651	2
2’-O-ANTHRANILOYL CGMP	0.012	1

Catalyzed reactions (Rhea), 1 shown:

• 3’,5’-cyclic GMP + H2O = GMP + H(+) (RHEA:16957)

UniProt features (74 total): helix 24, splice variant 14, mutagenesis site 11, binding site 10, turn 5, region of interest 2, compositionally biased region 2, chain 1, domain 1, modified residue 1, sequence conflict 1, strand 1, active site 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
4Y86	X-RAY DIFFRACTION	2.01
3DYN	X-RAY DIFFRACTION	2.1
3DY8	X-RAY DIFFRACTION	2.15
2HD1	X-RAY DIFFRACTION	2.23
3DYS	X-RAY DIFFRACTION	2.3
3JSW	X-RAY DIFFRACTION	2.3
3QI3	X-RAY DIFFRACTION	2.3
4G2J	X-RAY DIFFRACTION	2.4
6LZZ	X-RAY DIFFRACTION	2.4
3DYQ	X-RAY DIFFRACTION	2.5
3K3H	X-RAY DIFFRACTION	2.5
3QI4	X-RAY DIFFRACTION	2.5
4E90	X-RAY DIFFRACTION	2.5
6A3N	X-RAY DIFFRACTION	2.6
3DYL	X-RAY DIFFRACTION	2.7
3K3E	X-RAY DIFFRACTION	2.7
4GH6	X-RAY DIFFRACTION	2.7
4Y8C	X-RAY DIFFRACTION	2.7
7F0I	X-RAY DIFFRACTION	2.7
3JSI	X-RAY DIFFRACTION	2.72
3N3Z	X-RAY DIFFRACTION	2.75
2YY2	X-RAY DIFFRACTION	2.8
4G2L	X-RAY DIFFRACTION	3
4Y87	X-RAY DIFFRACTION	3.1
8BPY	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76083-F1	81.38	0.55

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): 312 (proton donor)

Ligand- & substrate-binding residues (10): 353; 353; 353; 462; 462; 484; 512–513; 312–316; 316; 352

Post-translational modifications (1): 379

Mutagenesis-validated functional residues (11):

Position	Phenotype
312	completely abolishes catalytic activity.
356	reduces catalytic activity, but has no effect on substrate affinity.
425	induces a 2 fold change in inhibitory sensitivity by bay-73-9961.
463	induces a 6-9 fold change in inhibitory sensitivity by bay-73-9961.
466	decreased affinity and catalytic activity for cgmp and camp.
480	induces a 6-9 fold change in inhibitory sensitivity by bay-73-9961.
484	induces a 6-9 fold change in inhibitory sensitivity by bay-73-9961.
501	induces a 2 fold change in inhibitory sensitivity by bay-73-9961.
513	induces a dramatic change in inhibitory sensitivity by bay-73-9961.
513	2 fold decreased affinity and catalytic activity for cgmp. 8 fold decreased catalytic activity for camp without affectin
516	induces a dramatic change in inhibitory sensitivity by bay-73-9961.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-418457	cGMP effects

MSigDB gene sets: 161 (showing top): GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CYCLIC_NUCLEOTIDE_METABOLIC_PROCESS, GOCC_RUFFLE, GOBP_CYCLIC_NUCLEOTIDE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CELL_CELL_SIGNALING, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, SOX9_B1, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_POSITIVE_REGULATION_OF_MUSCLE_HYPERTROPHY, GOBP_MUSCLE_ADAPTATION

GO Biological Process (7): signal transduction (GO:0007165), positive regulation of cardiac muscle hypertrophy (GO:0010613), cGMP metabolic process (GO:0046068), cGMP catabolic process (GO:0046069), negative regulation of cAMP/PKA signal transduction (GO:0141162), positive regulation of long-term synaptic potentiation (GO:1900273), negative regulation of neural precursor cell proliferation (GO:2000178)

GO Molecular Function (8): 3’,5’-cyclic-nucleotide phosphodiesterase activity (GO:0004114), 3’,5’-cyclic-AMP phosphodiesterase activity (GO:0004115), identical protein binding (GO:0042802), metal ion binding (GO:0046872), 3’,5’-cyclic-GMP phosphodiesterase activity (GO:0047555), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (12): nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), ruffle membrane (GO:0032587), sarcolemma (GO:0042383), perikaryon (GO:0043204), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Nitric oxide stimulates guanylate cyclase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
cytoplasm	4
3’,5’-cyclic-nucleotide phosphodiesterase activity	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cardiac muscle hypertrophy	1
regulation of cardiac muscle hypertrophy	1
positive regulation of muscle hypertrophy	1
purine ribonucleotide metabolic process	1
cyclic purine nucleotide metabolic process	1
purine ribonucleotide catabolic process	1
cyclic nucleotide catabolic process	1
cGMP metabolic process	1
cAMP/PKA signal transduction	1
regulation of cAMP/PKA signal transduction	1
negative regulation of intracellular signal transduction	1
positive regulation of synaptic transmission	1
long-term synaptic potentiation	1
regulation of long-term synaptic potentiation	1
negative regulation of cell population proliferation	1
neural precursor cell proliferation	1
regulation of neural precursor cell proliferation	1
cyclic-nucleotide phosphodiesterase activity	1
protein binding	1
cation binding	1
binding	1
phosphoric ester hydrolase activity	1
catalytic activity	1
nuclear lumen	1
membrane	1
cell periphery	1
ruffle	1
cell projection membrane	1
leading edge membrane	1
plasma membrane	1

Protein interactions and networks

STRING

854 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE9A	ALDH7A1	P49419	881
PDE9A	NDUFV3	P56181	792
PDE9A	TFF1	P04155	691
PDE9A	NDUFV2	P19404	650
PDE9A	NDUFV1	P49821	602
PDE9A	MT-ND1	P03886	549
PDE9A	MT-ND6	P03923	548
PDE9A	PDE6G	P18545	513
PDE9A	POU2F1	P14859	454
PDE9A	PGC	P20142	442
PDE9A	GNAO1	P09471	432
PDE9A	SLC37A1	P57057	424
PDE9A	PRKG1	P14619	417
PDE9A	TUBG1	P23258	416
PDE9A	NTRK2	Q16620	407

IntAct

84 interactions, top by confidence:

A	B	Type	Score
PDE9A	TRIM32	psi-mi:“MI:0915”(physical association)	0.880
TRIM32	PDE9A	psi-mi:“MI:0915”(physical association)	0.880
NOTCH2NLA	PDE9A	psi-mi:“MI:0915”(physical association)	0.670
PDE9A	GORASP2	psi-mi:“MI:0915”(physical association)	0.670
PDE9A	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.670
UNC119	UNC119B	psi-mi:“MI:0914”(association)	0.640
PDE9A	LINC02913	psi-mi:“MI:0915”(physical association)	0.560
PDE9A	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
	PDE9A	psi-mi:“MI:0915”(physical association)	0.560
PDE9A	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
PDE9A	KRTAP4-2	psi-mi:“MI:0915”(physical association)	0.560
PDE9A	BAG3	psi-mi:“MI:0915”(physical association)	0.560
PDE9A	LMO2	psi-mi:“MI:0915”(physical association)	0.560
CLK1	PDE9A	psi-mi:“MI:0915”(physical association)	0.560
SULT1E1	PDE9A	psi-mi:“MI:0915”(physical association)	0.560
LAGE3	PDE9A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (85): PDE9A (Two-hybrid), PDE9A (Two-hybrid), PDE9A (Two-hybrid), PDE9A (Two-hybrid), SULT1E1 (Two-hybrid), LAGE3 (Two-hybrid), BAG3 (Two-hybrid), TRIM32 (Two-hybrid), GORASP2 (Two-hybrid), TRPV6 (Two-hybrid), KRTAP9-2 (Two-hybrid), UTP23 (Two-hybrid), NAA38 (Two-hybrid), PHYHIPL (Two-hybrid), KRTAP4-2 (Two-hybrid)

ESM2 similar proteins: A2CEA7, A2XFW2, B2RR83, E9Q4S1, G5EDB9, H2QL32, I2HAA0, O00408, O14827, O16810, O18696, O60658, O70628, O76083, O88502, O95263, P14644, P14646, P19862, P27671, P28818, P30645, P54936, P70392, P93527, Q01062, Q01063, Q03606, Q07343, Q10MG9, Q13972, Q21653, Q22000, Q22070, Q58DC8, Q5R746, Q6NNF2, Q80Y84, Q8I0P7, Q8IRU4

Diamond homologs: B0G0Y8, B7YZV4, H2QL32, O00408, O08593, O18696, O70628, O76083, P06776, P14099, P14100, P54750, P70453, Q01061, Q01062, Q01064, Q01065, Q01066, Q13946, Q14123, Q1KKS3, Q23917, Q61481, Q63421, Q64338, Q64395, Q8I6Z7, Q8IKD3, Q8QZV1, Q922S4, Q9I7S6, Q9VJ79, B3LVW5, B3P3K2, B4G4E5, B4HEM4, B4JXX2, B4K9L4, B4LVU6, B4NAL6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NEURL1	“down-regulates quantity by destabilization”	PDE9A	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	89
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4563 predictions. Top by Δscore:

Variant	Effect	Δscore
21:42686261:CGGTG:C	donor_loss	1.0000
21:42686263:G:GG	donor_gain	1.0000
21:42687990:GAACG:G	donor_gain	1.0000
21:42733348:A:AG	acceptor_gain	1.0000
21:42733354:A:AG	acceptor_gain	1.0000
21:42733355:G:GG	acceptor_gain	1.0000
21:42733355:GA:G	acceptor_gain	1.0000
21:42733355:GAGC:G	acceptor_gain	1.0000
21:42733355:GAGCA:G	acceptor_gain	1.0000
21:42733427:G:GG	donor_gain	1.0000
21:42753988:A:AG	acceptor_gain	1.0000
21:42753989:G:GA	acceptor_gain	1.0000
21:42754062:GAG:G	donor_gain	1.0000
21:42754064:GGTA:G	donor_loss	1.0000
21:42754066:T:G	donor_loss	1.0000
21:42759076:G:GT	donor_gain	1.0000
21:42760324:GCA:G	acceptor_loss	1.0000
21:42760325:CAGT:C	acceptor_loss	1.0000
21:42760326:A:AG	acceptor_gain	1.0000
21:42760327:G:GC	acceptor_gain	1.0000
21:42760327:GT:G	acceptor_gain	1.0000
21:42760327:GTT:G	acceptor_gain	1.0000
21:42760327:GTTC:G	acceptor_gain	1.0000
21:42760327:GTTCT:G	acceptor_gain	1.0000
21:42760818:A:AG	acceptor_gain	1.0000
21:42760904:ACAC:A	donor_gain	1.0000
21:42760908:G:GG	donor_gain	1.0000
21:42760908:G:T	donor_loss	1.0000
21:42760909:T:A	donor_loss	1.0000
21:42762073:T:TA	acceptor_gain	1.0000

AlphaMissense

3966 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:42759080:T:A	W298R	1.000
21:42759080:T:C	W298R	1.000
21:42760361:T:C	F311L	1.000
21:42760363:C:A	F311L	1.000
21:42760363:C:G	F311L	1.000
21:42760364:C:G	H312D	1.000
21:42760376:C:G	H316D	1.000
21:42760381:C:G	C317W	1.000
21:42760879:G:C	D353H	1.000
21:42760880:A:C	D353A	1.000
21:42760880:A:G	D353G	1.000
21:42760880:A:T	D353V	1.000
21:42760881:T:A	D353E	1.000
21:42760881:T:G	D353E	1.000
21:42760883:T:C	L354P	1.000
21:42760888:C:G	H356D	1.000
21:42760889:A:G	H356R	1.000
21:42760890:T:A	H356Q	1.000
21:42760890:T:G	H356Q	1.000
21:42760902:C:A	N360K	1.000
21:42760902:C:G	N360K	1.000
21:42760905:C:A	N361K	1.000
21:42760905:C:G	N361K	1.000
21:42762084:T:A	Y363N	1.000
21:42762084:T:G	Y363D	1.000
21:42762096:G:C	A367P	1.000
21:42762103:C:T	T369I	1.000
21:42762120:T:G	Y375D	1.000
21:42762136:C:A	P380Q	1.000
21:42762136:C:G	P380R	1.000

dbSNP variants (sampled 300 via entrez): RS1000029706 (21:42679796 C>T), RS1000034107 (21:42729476 T>C), RS1000035298 (21:42669328 A>C), RS1000075858 (21:42699562 TTTTTTAA>T), RS1000085777 (21:42669531 A>G), RS1000088222 (21:42717062 A>G), RS1000158099 (21:42754238 A>G), RS1000183482 (21:42687436 G>A,T), RS1000194125 (21:42725793 C>T), RS1000220840 (21:42732562 G>A), RS1000235959 (21:42759219 C>T), RS1000253268 (21:42710558 A>G), RS1000286568 (21:42685015 A>C), RS1000308675 (21:42722269 C>T), RS1000338925 (21:42762265 C>T)

Disease associations

OMIM: gene MIM:602973 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004864_5	Perceived unattractiveness to mosquitoes	3.000000e-06
GCST90002383_100	Hematocrit	2.000000e-13
GCST90002384_494	Hemoglobin	4.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008380	perceived unattractiveness to mosquitos measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363066 (PROTEIN FAMILY), CHEMBL3535 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

9 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 105,844 (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
CHEMBL190461	CANNABIDIOL	4	26,379
CHEMBL192	SILDENAFIL	4	41,819
CHEMBL2179105	EDELINONTRINE	2	226
CHEMBL28079	ZAPRINAST	2	16,158
CHEMBL4206492	OSORESNONTRINE	2	32
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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
SCH51866	Inhibition	5.8	pIC50
zaprinast	Inhibition	4.5	pIC50

Binding affinities (BindingDB)

391 measured of 406 human assays (406 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-[methyl(1- pyrimidin-2- ylpropyl)amino]- 4-oxo-1-[1- [4-(trifluoro- methyl)phenyl] ethyl]-5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	0.01 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
6-[1-[5- (difluoromethyl) pyrimidin-2- yl]propyl- methyl- amino]-4-oxo- 1-[1-[6- (trifluoromethyl)- 3-pyridyl]- ethyl]-5H- pyrazolo[3,4- d]pyrimidine-3-carbonitrile	KI	0.01 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
1-[1-(4-cyclo- propylphenyl) ethyl]-6-[1-(5- fluoropyrimidin- 2-yl)propyl- methyl- amino]-4-oxo- 5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	0.02 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
ethyl 4-amino-6-methyl-2-phenylpyrimidine-5-carboxylate	KI	0.03 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
1-[1-(6- cyclopropyl-3- pyridyl)ethyl]- 6-[1-(5- fluoropyrimidin- 2-yl)propyl- methyl- amino]-4-oxo- 5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	0.03 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
6-[methyl(1- pyrimidin-2- ylpropyl)amino]- 4-oxo-1-[1- [6- (trifluoromethyl)- 3- pyridyl]ethyl]- 5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	0.14 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
6-[1-(5-fluoro- 2- pyridyl)propyl- methyl- amino]-4-oxo- 1-[1-[6- (trifluoromethyl)- 3-pyridyl]ethyl]- 5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	0.16 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
6-[1-(5- fluoropyrimidin- 2-yl)propyl- methyl- amino]-4-oxo- 1-(1- tetrahydropyran- 4-ylethyl)- 5H-pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	0.17 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
6-[methyl-[1- [5-(trifluoro- methoxy) pyrimidin-2- yl]propyl]- amino]-4-oxo- 1-[1-[6- (trifluoro- methyl)-3- pyridyl]ethyl]-5H-pyrazolo-d]pyrimidine-3-carbonitrile	KI	0.17 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
4-oxo-6-(2- pyrimidin-2- ylazetidin-1- yl)-1-[1-[6- (trifluoromethyl)- 3- pyridyl]ethyl]- 5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	0.23 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
4-oxo-6-(2- (pyrimidin-2- yl)butyl)-1-(1-(6- (trifluoromethyl) pyridin-3- yl)ethyl)-4,5- dihydro-1H- pyrazolo[3,4- d]pyrimidine-3- carbonitrile	KI	0.24 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
2-(4-bromophenyl)-4-methylphthalazin-1-one	KI	0.25 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
US20260001888, Example 77	KI	0.27 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
6-[methyl(1- pyrimidin-2- ylpent-4- enyl)amino]-4- oxo-1-[1-[6- (trifluoromethyl)- 3-pyridyl]ethyl]- 5H-pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	0.42 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
4-amino-2-[2-(2-fluorophenoxy)ethyl]isoindole-1,3-dione	KI	0.5 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
6-[1-(5-fluoro- 2- pyridyl)propyl- methyl- amino]-4-oxo- 1-[1-[6- (trifluoromethyl)- 3-pyridyl]ethyl]- 5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	0.59 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
6-[methyl-(2- methyl-1- pyrimidin-2- yl- propyl)amino]- 4-oxo-1-[1-[6- (trifluoromethyl)- 3-pyridyl]- ethyl]-5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	0.6 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
6-[2-(4- fluorophenyl) azetidin-1-yl]-4- oxo-1-[1-[6- (trifluoromethyl)- 3- pyridyl]ethyl]- 5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	0.6 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
1-[1-(6- cyclopropyl-3- pyridyl)ethyl]- 6-[1-(5- fluoropyrimidin- 2-yl)propyl- methyl- amino]-4-oxo- 5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	0.6 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
2-[(1-cyclopentyl-4-oxo-5,7a-dihydro-3aH-pyrazolo[3,4-d]pyrimidin-6-yl)amino]-N-(4-methoxyphenyl)propanamide	IC50	0.6 nM	US-9617269: N-substituted pyrazolo [3,4-D] pyrimidine ketone compound, and preparation process and use thereof
1-[1-(4- cyclopropylphenyl) ethyl]-6- [1-(5-fluoro- pyrimidin-2- yl)propyl- methyl- amino]-4-oxo- 5H- pyrazolo[3,4- d]pyrimidine-3-carbonitrile	KI	0.71 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
1-[1-(4- cyclopropylphenyl) ethyl]-6- [1-(5-fluoro- pyrimidin-2- yl)propyl- methyl- amino]-4-oxo- 5H- pyrazolo[3,4- d]pyrimidine-3-carbonitrile	KI	0.73 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
N-(4-methoxyphenyl)-2-[(4-oxo-1-propan-2-yl-3,3a,5,6,7,7a-hexahydro-2H-pyrazolo[3,4-d]pyrimidin-6-yl)amino]propanamide	IC50	1 nM	US-9617269: N-substituted pyrazolo [3,4-D] pyrimidine ketone compound, and preparation process and use thereof
6-[2-(4- fluorophenyl) azetidin-1-yl]-4- oxo-1-[1-[6- (trifluoromethyl)- 3- pyridyl]ethyl]- 5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	1.05 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
6-[methyl-[1- [5-(trifluoro- methoxy) pyrimidin-2- yl]propyl]amino]- 4-oxo-1-[1- [6-(trifluoro- methyl)-3- pyridyl]ethyl]- 5H-pyrazolo[3,4-d]pyrimidine-3-carbonitrile	KI	1.06 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
4-oxo-6-(2- (pyrimidin-2- yl)propyl)-1-(1- (6- (trifluoromethyl) pyridin-3- yl)ethyl)-4,5- dihydro-1H- pyrazolo[3,4- d]pyrimidine-3- carbonitrile	KI	1.17 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
6-[[cyclo- butyl(pyrimidin- 2-yl)methyl]- methyl- amino]-4-oxo- 1-[1-[6- (trifluoromethyl)- 3- pyridyl]ethyl]- 5H- pyrazolo[3,4- a]pyrimidine- 3-carbonitrile	KI	1.2 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
1-cyclohexyl-8-methoxy-N,N-dimethyl-4-oxo-8H-imidazo[1,5-a]quinoxaline-7-carboxamide	IC50	1.2 nM	US-8829000: Substituted imidazo[1,5-A]quinoxalines as phosphodiesterase 9 inhibitors
6-[1-[5- (difluoromethyl) pyrimidin-2- yl]propyl- methyl- amino]-4-oxo- 1-[1-[6- (trifluoromethyl)- 3-pyridyl]- ethyl]-5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	1.57 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
5-naphthalen-1-yl-3-pyridin-2-yl-1,2,4-oxadiazole	KI	1.82 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
US8623901, 239	IC50	2 nM	US-8623901: Compounds for the treatment of CNS disorders
3-(7-ethyl-4-oxo-9aH-imidazo[1,5-a]quinoxalin-1-yl)propanoic acid	IC50	2 nM	US-8829000: Substituted imidazo[1,5-A]quinoxalines as phosphodiesterase 9 inhibitors
3-[4-oxo-7-(trifluoromethyl)-9aH-imidazo[1,5-a]quinoxalin-1-yl]propanoic acid	IC50	2 nM	US-8829000: Substituted imidazo[1,5-A]quinoxalines as phosphodiesterase 9 inhibitors
6-[1-[5- (difluoromethyl) pyrimidin-2- yl]propyl- methyl- amino]-4-oxo- 1-[1-[6- (trifluoromethyl)- 3- pyridyl]ethyl]- 5H- pyrazolo[3,4-d]pyrimidine-3-carbonitrile	KI	2.07 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
6-[methyl(1- pyrimidin-2- ylethyl)amino]- 4-oxo-1-[1-[6- (trifluoromethyl)- 3- pyridyl]ethyl]- 5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	2.3 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
6-[1-(5- fluoropyrimidin- 2-yl)propyl- methyl- amino]-4-oxo- 1-(1- tetrahydropyran- 4-ylethyl)- 5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	2.67 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
6-[methyl(1- pyrimidin-2- ylpropyl)amino]- 4-oxo-1-[1- [4-(trifluoro- methyl)phenyl] ethyl]-5H- pyrazolo[3,4- d]pyrimidine- 3-carbonitrile	KI	2.82 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
US8623901, 234	IC50	3 nM	US-8623901: Compounds for the treatment of CNS disorders
8-chloro-1-cyclohexyl-N,N-dimethyl-4-oxo-8H-imidazo[1,5-a]quinoxaline-7-carboxamide	IC50	3 nM	US-8829000: Substituted imidazo[1,5-A]quinoxalines as phosphodiesterase 9 inhibitors
3-(7-bromo-4-oxo-9aH-imidazo[1,5-a]quinoxalin-1-yl)propanoic acid	IC50	3 nM	US-8829000: Substituted imidazo[1,5-A]quinoxalines as phosphodiesterase 9 inhibitors
2-[(1-cyclopentyl-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl)amino]-N-(4-methoxyphenyl)propanamide	IC50	3 nM	US-9617269: N-substituted pyrazolo [3,4-D] pyrimidine ketone compound, and preparation process and use thereof
6-(cyclopropanecarbonyl)-4-(4-methoxy-4-methylpiperidin-1-yl)-2-oxo-1H-1,7-naphthyridine-3-carbonitrile	IC50	3 nM	US-10889591: PDE9 inhibitor and use thereof
4,6-dibromo-2-phenyl-1,3-benzoxazol-5-amine	KI	3.2 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
N-[(3-chlorophenyl)carbamoyl]-2-methoxybenzamide	KI	3.31 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
1-cyclohexyl-8-ethoxy-N,N-dimethyl-4-oxo-8H-imidazo[1,5-a]quinoxaline-7-carboxamide	IC50	3.4 nM	US-8829000: Substituted imidazo[1,5-A]quinoxalines as phosphodiesterase 9 inhibitors
2-oxo-4-[3- (pyridin-3-yl) pyrrolidin-1- yl]-1,2- dihydroquinoline- 3-carbonitrile	KI	3.4 nM	US-10370336: Phenyl-cyanoquinolinone PDE9 inhibitors
N-(3-methoxyphenyl)-4-methylindazole-1-carboxamide	KI	3.96 nM	US-20260001888: PYRAZOLOPYRIMIDINE PDE9 INHIBITORS
US8623901, 261	IC50	4 nM	US-8623901: Compounds for the treatment of CNS disorders
1-(4,4-difluorocyclohexyl)-6-(2-pyrimidin-2-ylcyclobutyl)-3,3a,5,6,7,7a-hexahydro-2H-pyrazolo[3,4-d]pyrimidin-4-one	IC50	4 nM	US-9328120: 6-cycloalkyl-pyrazolopyrimidinones for the treatment of CNS disorders
6-[(4-chlorophenyl)methylamino]-1-cyclopentyl-5H-pyrazolo[5,4-d]pyrimidin-4-one	IC50	4 nM	US-9617269: N-substituted pyrazolo [3,4-D] pyrimidine ketone compound, and preparation process and use thereof

ChEMBL bioactivities

1287 potent at pChembl≥5 of 1301 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL5823889
11.00	Ki	0.01	nM	CHEMBL5898437
11.00	Ki	0.01	nM	CHEMBL6042821
11.00	Ki	0.01	nM	CHEMBL6066018
10.70	Ki	0.02	nM	CHEMBL5995578
10.52	Ki	0.03	nM	CHEMBL5791216
10.52	Ki	0.03	nM	CHEMBL5810180
10.40	Ki	0.04	nM	CHEMBL5978036
10.40	Ki	0.04	nM	CHEMBL5994306
10.40	Ki	0.04	nM	CHEMBL5918399
10.40	Ki	0.04	nM	CHEMBL5792042
10.30	Ki	0.05	nM	CHEMBL5831897
10.10	Ki	0.08	nM	CHEMBL5814476
10.05	Ki	0.09	nM	CHEMBL5934210
10.00	IC50	0.1	nM	CHEMBL5081214
10.00	Ki	0.1	nM	CHEMBL6021225
10.00	Ki	0.1	nM	CHEMBL5844711
10.00	Ki	0.1	nM	CHEMBL5783455
9.92	Ki	0.12	nM	CHEMBL5804006
9.90	IC50	0.1259	nM	CHEMBL5080391
9.89	Ki	0.13	nM	CHEMBL5986222
9.89	Ki	0.13	nM	CHEMBL5900169
9.82	Ki	0.15	nM	CHEMBL5956047
9.80	IC50	0.1585	nM	CHEMBL5087564
9.74	Ki	0.18	nM	CHEMBL5949686
9.70	Ki	0.2	nM	CHEMBL5987380
9.70	Ki	0.2	nM	CHEMBL5842454
9.66	Ki	0.22	nM	CHEMBL5745526
9.64	Ki	0.23	nM	CHEMBL5812652
9.60	IC50	0.2512	nM	CHEMBL5094110
9.60	Ki	0.25	nM	CHEMBL5897948
9.57	Ki	0.27	nM	CHEMBL5919114
9.52	Ki	0.3	nM	CHEMBL5963276
9.52	Ki	0.3	nM	CHEMBL5889220
9.50	IC50	0.3162	nM	CHEMBL5086895
9.50	IC50	0.3162	nM	CHEMBL5076558
9.40	Ki	0.4	nM	CHEMBL5749511
9.30	IC50	0.5	nM	CHEMBL5641637
9.30	Ki	0.5	nM	CHEMBL5856898
9.22	IC50	0.6	nM	CHEMBL3360415
9.22	IC50	0.6	nM	CHEMBL5913347
9.15	Ki	0.7	nM	CHEMBL5760139
9.15	Ki	0.7	nM	CHEMBL5926636
9.10	IC50	0.8	nM	CHEMBL572934
9.10	Ki	0.8	nM	CHEMBL5898437
9.05	IC50	0.9	nM	CHEMBL2179099
9.05	Ki	0.9	nM	CHEMBL5745526
9.00	IC50	1	nM	CHEMBL2179093
9.00	IC50	1	nM	CHEMBL5078680
9.00	IC50	1	nM	CHEMBL5088742

PubChem BioAssay actives

287 with measured affinity, of 663 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
6-[(1S,2S)-2-(6-methylimidazo[1,2-b]pyridazin-2-yl)cyclobutyl]-1-(oxan-4-yl)-5H-pyrazolo[5,4-d]pyrimidin-4-one	2140282: Inhibition of human PDE9A2 expressed in Sf9 cells using cGMP as substrate by scintillation proximity assay	ic50	0.0005	uM
(2R)-2-[(1-cyclopentyl-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl)amino]-N-(4-methoxyphenyl)propanamide	1171940: Inhibition of PDE9A2 catalytic domain (unknown origin) using [3H]-cGMP/[3H]-cAMP as substrate after 15 mins by liquid scintillation counting analysis	ic50	0.0006	uM
6-benzyl-1-cyclopentyl-5H-pyrazolo[5,4-d]pyrimidin-4-one	708596: Inhibition of human recombinant PDE9A expressed in Sf9 cells using [3H]cGMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0008	uM
6-[(3S,4S)-1-[(4-fluorophenyl)methyl]-4-methylpyrrolidin-3-yl]-1-(oxan-4-yl)-5H-pyrazolo[5,4-d]pyrimidin-4-one	708596: Inhibition of human recombinant PDE9A expressed in Sf9 cells using [3H]cGMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0009	uM
6-benzyl-1-(oxan-4-yl)-5H-pyrazolo[5,4-d]pyrimidin-4-one	708596: Inhibition of human recombinant PDE9A expressed in Sf9 cells using [3H]cGMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0010	uM
(2R)-N-(4-methoxyphenyl)-2-[(4-oxo-1-propan-2-yl-5H-pyrazolo[5,4-d]pyrimidin-6-yl)amino]propanamide	1171940: Inhibition of PDE9A2 catalytic domain (unknown origin) using [3H]-cGMP/[3H]-cAMP as substrate after 15 mins by liquid scintillation counting analysis	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
(2R)-2-[(1-cyclopentyl-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl)amino]-N-(4-fluorophenyl)propanamide	1171940: Inhibition of PDE9A2 catalytic domain (unknown origin) using [3H]-cGMP/[3H]-cAMP as substrate after 15 mins by liquid scintillation counting analysis	ic50	0.0011	uM
(5Z)-5-[[4-[2-[(1-cyclopentyl-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl)amino]ethoxy]-3-fluorophenyl]methylidene]-1,3-thiazolidine-2,4-dione	2124217: Inhibition of PDE9A (unknown origin)	ic50	0.0011	uM
6-[(3S,4S)-1-[(3-fluorophenyl)methyl]-4-methylpyrrolidin-3-yl]-1-(oxan-4-yl)-5H-pyrazolo[5,4-d]pyrimidin-4-one	708596: Inhibition of human recombinant PDE9A expressed in Sf9 cells using [3H]cGMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0012	uM
methyl 5-[2,4-dioxo-6-(3-propan-2-ylphenyl)-3-propyl-5H-pyrrolo[3,2-d]pyrimidin-1-yl]-2,3-dihydro-1H-isoindole-1-carboxylate	2124218: Binding affinity to PDE9A (unknown origin) using [3H]cAMP as substrate assessed as inhibition constant incubated for 1 hr by SPR assay	ki	0.0015	uM
6-[(3S,4S)-1-benzyl-4-ethylpyrrolidin-3-yl]-1-(oxan-4-yl)-5H-pyrazolo[5,4-d]pyrimidin-4-one	708596: Inhibition of human recombinant PDE9A expressed in Sf9 cells using [3H]cGMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0017	uM
1-cyclopentyl-6-[(3S,4S)-4-methyl-1-(quinoxalin-6-ylmethyl)pyrrolidin-3-yl]-5H-pyrazolo[5,4-d]pyrimidin-4-one	442319: Inhibition of human recombinant PDE9A expressed in Sf9 cells by SPA	ic50	0.0018	uM
(2R)-2-[(1-cyclopentyl-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl)amino]-N-(1H-indazol-5-yl)propanamide	1663808: Inhibition of PDE9A (unknown origin)	ic50	0.0018	uM
1-cyclopentyl-6-[(3R,4R)-4-methyl-1-(quinoxalin-6-ylmethyl)pyrrolidin-3-yl]-5H-pyrazolo[5,4-d]pyrimidin-4-one	442319: Inhibition of human recombinant PDE9A expressed in Sf9 cells by SPA	ic50	0.0019	uM
(2R)-N-(3H-benzimidazol-5-yl)-2-[(1-cyclopentyl-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl)amino]propanamide	1663808: Inhibition of PDE9A (unknown origin)	ic50	0.0020	uM
6-benzyl-1-cyclopentyl-5H-pyrazolo[4,5-c]pyridin-4-one	2140279: Inhibition of PDE9A (unknown origin) by high-throughput screening analysis	ic50	0.0020	uM
(2R)-2-[(1-cyclopentyl-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl)amino]-N-imidazo[1,2-a]pyridin-6-ylpropanamide	1663808: Inhibition of PDE9A (unknown origin)	ic50	0.0021	uM
1-cyclopentyl-6-[4-methyl-1-(quinoxalin-6-ylmethyl)pyrrolidin-3-yl]-5H-pyrazolo[5,4-d]pyrimidin-4-one	1395053: Inhibition of recombinant GST-tagged human PDE9A2 expressed in insect cells using cGMP as substrate after 1 hr by IMAP TR-FRET assay	ic50	0.0028	uM
(2S)-2-[(1-cyclopentyl-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl)amino]-N-(4-methoxyphenyl)propanamide	1171940: Inhibition of PDE9A2 catalytic domain (unknown origin) using [3H]-cGMP/[3H]-cAMP as substrate after 15 mins by liquid scintillation counting analysis	ic50	0.0030	uM
4-(6-azaspiro[2.5]octan-6-yl)-2-oxo-1H-1,7-naphthyridine-3-carbonitrile	2140293: Inhibition of PDE9A2 (unknown origin)	ic50	0.0030	uM
6-[2-(2,3-dihydroindol-1-yl)-2-oxoethyl]-4-(4-methylphenyl)-2-oxo-8-propyl-1,5,7,8-tetrahydro-1,6-naphthyridine-3-carbonitrile	1897883: Inhibition of full length human PDE9A expressed in Sf9 insect cells using [3H]-cGMP as substrate incubated for 60 mins by microbeta scintillation counter analysis	ic50	0.0030	uM
6-[(3S,4S)-1-[(4-methoxyphenyl)methyl]-4-methylpyrrolidin-3-yl]-1-(oxan-4-yl)-5H-pyrazolo[5,4-d]pyrimidin-4-one	708596: Inhibition of human recombinant PDE9A expressed in Sf9 cells using [3H]cGMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0034	uM
6-[(3S,4S)-4-methyl-1-[(6-methyl-3-pyridinyl)methyl]pyrrolidin-3-yl]-1-(oxan-4-yl)-5H-pyrazolo[5,4-d]pyrimidin-4-one	708596: Inhibition of human recombinant PDE9A expressed in Sf9 cells using [3H]cGMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0038	uM
1-(4,4-difluorocyclohexyl)-6-[(1S,2S)-2-pyrimidin-2-ylcyclobutyl]-5H-pyrazolo[5,4-d]pyrimidin-4-one	2140282: Inhibition of human PDE9A2 expressed in Sf9 cells using cGMP as substrate by scintillation proximity assay	ic50	0.0040	uM
6-[(3S,4S)-4-methyl-1-[(2-methylpyrimidin-5-yl)methyl]pyrrolidin-3-yl]-1-(oxan-4-yl)-5H-pyrazolo[5,4-d]pyrimidin-4-one	708596: Inhibition of human recombinant PDE9A expressed in Sf9 cells using [3H]cGMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0046	uM
6-[(3S,4S)-1-[(2-fluorophenyl)methyl]-4-methylpyrrolidin-3-yl]-1-(oxan-4-yl)-5H-pyrazolo[5,4-d]pyrimidin-4-one	708596: Inhibition of human recombinant PDE9A expressed in Sf9 cells using [3H]cGMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0046	uM
6-[(3S,4S)-1-benzyl-4-methylpyrrolidin-3-yl]-1-(oxan-4-yl)-5H-pyrazolo[5,4-d]pyrimidin-4-one	708596: Inhibition of human recombinant PDE9A expressed in Sf9 cells using [3H]cGMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0049	uM
4-[4-(2-hydroxyethyl)piperidin-1-yl]-2-[[2-(6-methoxy-3-pyridinyl)phenyl]methyl]-6-oxo-1H-pyrimidine-5-carbonitrile	2140271: Inhibition of PDE9A (unknown origin)	ic50	0.0050	uM
[4-[5-hydroxy-8,8-dimethyl-6-(3-methylbut-2-enyl)-4-oxo-9,10-dihydropyrano[2,3-h]chromen-3-yl]-2-methylsulfonyloxyphenyl] methanesulfonate	2124217: Inhibition of PDE9A (unknown origin)	ic50	0.0053	uM
6-[[(2R)-1-(4-chloropiperidin-1-yl)-1-oxopropan-2-yl]amino]-1-cyclopentyl-5H-pyrazolo[5,4-d]pyrimidin-4-one	1812074: Inhibition of PDE9A2 (181 to 506 residues) (unknown origin) using [3H]-cGMP substrate measured for 15 mins by liquid scintillation counting method	ic50	0.0054	uM
2-[(1-cyclopentyl-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl)amino]-N-(4-methoxyphenyl)acetamide	1171940: Inhibition of PDE9A2 catalytic domain (unknown origin) using [3H]-cGMP/[3H]-cAMP as substrate after 15 mins by liquid scintillation counting analysis	ic50	0.0055	uM
4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)-2-oxo-8-propyl-5,6,7,8-tetrahydro-1H-1,6-naphthyridine-3-carbonitrile;2,2,2-trifluoroacetic acid	1897883: Inhibition of full length human PDE9A expressed in Sf9 insect cells using [3H]-cGMP as substrate incubated for 60 mins by microbeta scintillation counter analysis	ic50	0.0060	uM
6-[(3S,4S)-4-methyl-1-(pyridin-2-ylmethyl)pyrrolidin-3-yl]-1-(oxan-4-yl)-5H-pyrazolo[5,4-d]pyrimidin-4-one	708596: Inhibition of human recombinant PDE9A expressed in Sf9 cells using [3H]cGMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0063	uM
(2R)-2-[[1-(2-chlorophenyl)-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl]amino]-N-(4-methoxyphenyl)propanamide	1171940: Inhibition of PDE9A2 catalytic domain (unknown origin) using [3H]-cGMP/[3H]-cAMP as substrate after 15 mins by liquid scintillation counting analysis	ic50	0.0064	uM
2-[[(1R,2S)-2-[(7-oxo-3-propan-2-yl-2,6-dihydropyrazolo[4,3-d]pyrimidin-5-yl)methyl]cyclohexyl]amino]-4-(trifluoromethyl)pyrimidine-5-carboxylic acid	352678: Inhibition of human recombinant PDE9 expressed in SF9 cells by scintillation proximity assay	ic50	0.0070	uM
1-(oxan-4-yl)-6-[(1R)-1-(3-pyrimidin-2-yloxyazetidin-1-yl)ethyl]-5H-pyrazolo[5,4-d]pyrimidin-4-one	705568: Inhibition of PDE9A using [3H]cGMP as substrate after 30 mins by scintillation proximity assay	ic50	0.0070	uM
(2R)-2-[(1-cyclopentyl-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl)amino]-N-(6-fluoro-3-pyridinyl)propanamide	1663808: Inhibition of PDE9A (unknown origin)	ic50	0.0070	uM
1-cyclopentyl-6-[[(2R)-1-(6-fluoro-2-azaspiro[3.3]heptan-2-yl)-1-oxopropan-2-yl]amino]-5H-pyrazolo[5,4-d]pyrimidin-4-one	1812116: Binding affinity to PDE9A2 (unknown origin)	ki	0.0070	uM
6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(oxan-4-yl)-5H-pyrazolo[5,4-d]pyrimidin-4-one	1895838: Inhibition of PDE9A (unknown origin)	ic50	0.0080	uM
(E)-N-hydroxy-3-[4-[[(3R,4R)-3-methyl-4-[1-(oxan-4-yl)-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl]pyrrolidin-1-yl]methyl]phenyl]prop-2-enamide	1858588: Inhibition of PDE9 (unknown origin)	ic50	0.0080	uM
(2R)-2-[(1-cyclopentyl-4-oxo-5H-pyrazolo[5,4-d]pyrimidin-6-yl)amino]-N-(4-methoxyphenyl)-4-methylpentanamide	1171940: Inhibition of PDE9A2 catalytic domain (unknown origin) using [3H]-cGMP/[3H]-cAMP as substrate after 15 mins by liquid scintillation counting analysis	ic50	0.0081	uM
6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-3-(oxan-4-yl)-7H-imidazo[1,5-a]pyrazin-8-one	1872592: Inhibition of recombinant human PDE9A1 by radiometric assay	ic50	0.0082	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	6
Valproic Acid	increases methylation, affects expression, decreases expression	5
trichostatin A	affects cotreatment, decreases expression	3
Tobacco Smoke Pollution	decreases expression, decreases methylation, increases expression	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
Nickel	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tretinoin	decreases expression	2
Cyclosporine	increases expression, decreases expression	2
Particulate Matter	increases abundance, increases expression	2
chloroacetaldehyde	decreases expression	1
bisphenol A	increases methylation	1
zaprinast	increases hydrolysis, decreases reaction	1
terbufos	increases methylation	1
sulforaphane	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
nickel sulfate	increases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
celastrol	decreases expression	1
CGP 52608	affects binding, increases reaction	1
gedunin	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Cyclic AMP	increases hydrolysis	1
Air Pollutants	increases abundance, increases expression	1
Carbamazepine	affects expression	1

ChEMBL screening assays

230 unique, capped per target: 223 binding, 6 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4479636	Binding	Inhibition of human PDE	Discovery of novel potent imidazo[1,2-b]pyridazine PDE10a inhibitors. — Bioorg Med Chem Lett
CHEMBL4680008	ADMET	Inhibition of PDE (unknown origin)	Fragment-Based Discovery of Novel Allosteric MEK1 Binders. — ACS Med Chem Lett
CHEMBL5723180	Functional	Affinity Biochemical interaction: (inhibition of enzyme activity with [3H]cGMP or [3H]cAMP as the substrate) EUB0002477a PDE9A	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Clinical trials (associated diseases)

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