PDE7A

Summary

PDE7A (phosphodiesterase 7A, HGNC:8791) is a protein-coding gene on chromosome 8q13.1, encoding High affinity 3’,5’-cyclic-AMP phosphodiesterase 7A (Q13946). Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE7 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 5150 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 5 total
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001242318

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8791
Approved symbol	PDE7A
Name	phosphodiesterase 7A
Location	8q13.1
Locus type	gene with protein product
Status	Approved
Aliases	HCP1
Ensembl gene	ENSG00000205268
Ensembl biotype	protein_coding
OMIM	171885
Entrez	5150

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000379419, ENST00000396642, ENST00000401827, ENST00000518667, ENST00000519231, ENST00000519626, ENST00000522220, ENST00000523253, ENST00000935327, ENST00000935328, ENST00000935329, ENST00000935330, ENST00000935331

RefSeq mRNA: 2 — MANE Select: NM_001242318 NM_001242318, NM_002603

CCDS: CCDS34901, CCDS56538

Canonical transcript exons

ENST00000401827 — 13 exons

Exon	Start	End
ENSE00001480907	65714334	65719495
ENSE00001480908	65723541	65723621
ENSE00001480909	65724255	65724351
ENSE00001480910	65724777	65724921
ENSE00001480911	65726875	65726966
ENSE00002122953	65841371	65842064
ENSE00003510612	65747652	65747803
ENSE00003531982	65745407	65745470
ENSE00003559144	65779720	65779803
ENSE00003580103	65727170	65727301
ENSE00003615863	65782783	65782843
ENSE00003630008	65734794	65734894
ENSE00003669371	65739502	65739597

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.3563 / max 286.3154, expressed in 1529 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93368	4.9053	1174
93367	1.6665	573
93370	0.8636	272
93366	0.8386	446
93365	0.8257	378
93364	0.6620	315
93356	0.4239	51
93369	0.3611	197
93362	0.3604	188
93361	0.2443	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.30	gold quality
thymus	UBERON:0002370	97.98	gold quality
oocyte	CL:0000023	96.67	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.61	gold quality
apex of heart	UBERON:0002098	95.39	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.88	gold quality
lymph node	UBERON:0000029	94.43	gold quality
gastrocnemius	UBERON:0001388	94.39	gold quality
deltoid	UBERON:0001476	94.36	gold quality
skeletal muscle tissue	UBERON:0001134	94.10	gold quality
muscle of leg	UBERON:0001383	94.05	gold quality
vermiform appendix	UBERON:0001154	93.61	gold quality
right atrium auricular region	UBERON:0006631	93.58	gold quality
heart left ventricle	UBERON:0002084	93.49	gold quality
cardiac ventricle	UBERON:0002082	93.40	gold quality
cardiac atrium	UBERON:0002081	93.22	gold quality
biceps brachii	UBERON:0001507	92.60	gold quality
quadriceps femoris	UBERON:0001377	92.55	gold quality
tibialis anterior	UBERON:0001385	92.50	gold quality
granulocyte	CL:0000094	92.36	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.27	gold quality
vastus lateralis	UBERON:0001379	92.26	gold quality
tonsil	UBERON:0002372	92.10	gold quality
muscle tissue	UBERON:0002385	92.06	gold quality
blood	UBERON:0000178	91.89	gold quality
epithelium of nasopharynx	UBERON:0001951	91.89	gold quality
heart	UBERON:0000948	91.64	gold quality
ganglionic eminence	UBERON:0004023	91.42	gold quality
left ventricle myocardium	UBERON:0006566	91.17	gold quality
spleen	UBERON:0002106	90.98	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	172.73
E-ANND-3	yes	11.06
E-MTAB-11268	no	972.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS2, NFKB1

miRNA regulators (miRDB)

299 targeting PDE7A, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-188-3P	100.00	68.76	1240
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593

Literature-anchored findings (GeneRIF, showing 12)

• PDE7 has the potential to regulate human T cell function including cytokine production, proliferation and expression of activation markers. (PMID:12067300)
• Ubiquitous expression of phosphodiesterase 7A in human proinflammatory and immune cells; PDE7A was expressed in neutrophils and alveolar macrophages (PMID:12388353)
• crystal structure of PDE7A1 catalytic domain complexed with the inhibitor 3-isobutyl-1-methylxanthine & kinetic analysis on mutant PDE7A1 and PDE4D2; results show several residues must work together to switch inhibitor selectivity between PDE4 & PDE7 (PMID:15994308)
• results show that specific gene silencing with the RNAi method is a useful tool for inhibiting the gene expression of specific PDEs and that PDE7 silencing upregulates several osteogenic genes and increases mineralization (PMID:18420479)
• PDE7 has roles in regulating oligodendrocyte precursor survival and differentiation during brain development and in adulthood (PMID:23661015)
• PDE7A is a high-speed and low-affinity phosphodiesterase for cCMP. (PMID:25128584)
• Low PDE7A expression is associated with sepsis. (PMID:28356347)
• Here we describe a compound, BC54, that is a selective inhibitor of enzymes from the cAMP-specific PDE4 and PDE7 families. Consistent with the biological effect of other PDE4 and PDE7 inhibitors, BC54 displays potent anti-inflammatory properties and is superior to a combination of rolipram (a PDE4 inhibitor) and BRL50481 (a PDE7A inhibitor) for inducing apoptosis in chronic lymphocytic leukemia (CLL) cells (PMID:28867658)
• Phosphodiesterase 7 Regulation in Cellular and Rodent Models of Parkinson’s Disease. (PMID:31473904)
• Long non-coding RNA TUSC7 suppressed colorectal cancer progression via regulation of miR-23b/PDE7A Axis. (PMID:33370523)
• Circ_0091702 relieves lipopolysaccharide (LPS)-induced cell injury by regulating the miR-182/PDE7A axis in sepsis. (PMID:34077501)
• The habenular volume and PDE7A allelic polymorphism in major depressive disorder: preliminary findings. (PMID:35673941)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	pde7a	ENSDARG00000045305
mus_musculus	Pde7a	ENSMUSG00000069094
rattus_norvegicus	Pde7a	ENSRNOG00000013048
drosophila_melanogaster	Pde11	FBGN0085370
drosophila_melanogaster	Pde8	FBGN0266377
caenorhabditis_elegans		WBGENE00008443
caenorhabditis_elegans	pde-6	WBGENE00022389

Paralogs (20): PDE4A (ENSG00000065989), PDE8A (ENSG00000073417), PDE6C (ENSG00000095464), PDE4C (ENSG00000105650), PDE10A (ENSG00000112541), PDE8B (ENSG00000113231), PDE4D (ENSG00000113448), PDE1A (ENSG00000115252), PDE1B (ENSG00000123360), PDE11A (ENSG00000128655), PDE6A (ENSG00000132915), PDE6B (ENSG00000133256), PDE5A (ENSG00000138735), PDE3B (ENSG00000152270), PDE1C (ENSG00000154678), PDE9A (ENSG00000160191), PDE7B (ENSG00000171408), PDE3A (ENSG00000172572), PDE4B (ENSG00000184588), PDE2A (ENSG00000186642)

Protein

Protein identifiers

High affinity 3’,5’-cyclic-AMP phosphodiesterase 7A — Q13946 (reviewed: Q13946)

Alternative names: HCP1, TM22, cAMP-specific phosphodiesterase 7A

All UniProt accessions (2): Q13946, E5RG23

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May have a role in muscle signal transduction.

Subunit / interactions. Interacts with CBFA2T3.

Subcellular location. Cytoplasm. Cytosol Cytoplasm.

Tissue specificity. Found at high levels in skeletal muscle and at low levels in a variety of tissues including brain and heart. It is expressed as well in two T-cell lines. Found abundantly in skeletal muscle and at low levels in heart.

Activity regulation. Insensitive to all selective PDE inhibitors.

Cofactor. Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.

Domain organisation. Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain.

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

Similarity. Belongs to the cyclic nucleotide phosphodiesterase family. PDE7 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13946-1	PDE7A1	yes
Q13946-2	PDE7A2
Q13946-3	PDE7A3

RefSeq proteins (2): NP_001229247, NP_002594 (=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 3.1.4.53 — 3’,5’-cyclic-AMP phosphodiesterase (BRENDA: 28 organisms, 62 substrates, 307 inhibitors, 60 Km, 12 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ADENOSINE 3’,5’-CYCLIC PHOSPHATE	—	34
3’,5’-CAMP	0.0003–0.5	13
CAMP	0.0001–0.191	9
CGMP	0.24–0.427	2
3’,5’-CGMP	1.6	1
GUANOSINE 3’,5’-CYCLIC PHOSPHATE	0.124	1

Catalyzed reactions (Rhea), 1 shown:

• 3’,5’-cyclic AMP + H2O = AMP + H(+) (RHEA:25277)

UniProt features (40 total): helix 20, turn 5, binding site 5, splice variant 3, chain 1, domain 1, sequence variant 1, sequence conflict 1, active site 1, strand 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1ZKL	X-RAY DIFFRACTION	1.67
4PM0	X-RAY DIFFRACTION	2.1
4Y2B	X-RAY DIFFRACTION	2.2
3G3N	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13946-F1	78.50	0.65

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): 212 (proton donor)

Ligand- & substrate-binding residues (5): 216; 252; 253; 253; 362

Post-translational modifications (1): 84

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 322 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, FREAC2_01, TGCGCANK_UNKNOWN, LU_IL4_SIGNALING, NKX25_02, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CYCLIC_NUCLEOTIDE_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_CYCLIC_NUCLEOTIDE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS

GO Biological Process (3): cAMP catabolic process (GO:0006198), signal transduction (GO:0007165), negative regulation of cAMP/PKA signal transduction (GO:0141162)

GO Molecular Function (7): 3’,5’-cyclic-AMP phosphodiesterase activity (GO:0004115), metal ion binding (GO:0046872), 3’,5’-cyclic-GMP phosphodiesterase activity (GO:0047555), cyclic-nucleotide phosphodiesterase activity (GO:0004112), 3’,5’-cyclic-nucleotide phosphodiesterase activity (GO:0004114), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
3’,5’-cyclic-nucleotide phosphodiesterase activity	2
cellular anatomical structure	2
purine ribonucleotide catabolic process	1
cyclic nucleotide catabolic process	1
cAMP metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cAMP/PKA signal transduction	1
regulation of cAMP/PKA signal transduction	1
negative regulation of intracellular signal transduction	1
cation binding	1
phosphoric diester hydrolase activity	1
cyclic-nucleotide phosphodiesterase activity	1
phosphoric ester hydrolase activity	1
catalytic activity	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

832 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE7A	ALDH7A1	P49419	949
PDE7A	PDE10A	Q9Y233	543
PDE7A	PDE6D	O43924	523
PDE7A	ZNF451	Q9Y4E5	507
PDE7A	AKAP8	O43823	485
PDE7A	RAPGEF4	Q8WZA2	455
PDE7A	RAPGEF3	O95398	445
PDE7A	PRKACA	P17612	422
PDE7A	PRKACB	P22694	416
PDE7A	PRKACG	P22612	415
PDE7A	GUCY2C	P25092	414
PDE7A	ADCY6	O43306	411
PDE7A	MTFR1	Q15390	388
PDE7A	AKAP6	Q13023	374
PDE7A	NT5E	P21589	369

IntAct

16 interactions, top by confidence:

A	B	Type	Score
PRKACA	VAPB	psi-mi:“MI:0914”(association)	0.730
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
UBXN11	COL1A1	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
PRKACA	ZNF724	psi-mi:“MI:0914”(association)	0.350
YWHAB	BRAF	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
LOX	VWA8	psi-mi:“MI:0914”(association)	0.350
PTH2R	METTL15	psi-mi:“MI:0914”(association)	0.350
THBS3	APBB1	psi-mi:“MI:0914”(association)	0.350
PNMA6A	ZFTRAF1	psi-mi:“MI:0914”(association)	0.350
PDE7A	AIP	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	PDE7A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): PDE7A (Affinity Capture-MS), VPS13A (Affinity Capture-MS), PDE7A (Affinity Capture-MS), PDE7A (Affinity Capture-MS), PDE7A (Affinity Capture-MS), PDE7A (Affinity Capture-MS), PDE7A (Affinity Capture-MS), PDE7A (Affinity Capture-MS), PDE7A (Affinity Capture-MS), PDE7A (Affinity Capture-MS), PDE7A (Affinity Capture-MS), PDE7A (Affinity Capture-MS), VPS13A (Affinity Capture-MS), AIP (Affinity Capture-MS), PDF (Affinity Capture-MS)

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: 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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2097 predictions. Top by Δscore:

Variant	Effect	Δscore
8:65723540:CCAAT:C	donor_gain	1.0000
8:65723544:T:C	donor_gain	1.0000
8:65724243:A:AC	donor_gain	1.0000
8:65724244:C:CC	donor_gain	1.0000
8:65724249:A:C	donor_gain	1.0000
8:65724347:GCCAT:G	acceptor_gain	1.0000
8:65724348:CCAT:C	acceptor_gain	1.0000
8:65724348:CCATC:C	acceptor_gain	1.0000
8:65724349:CAT:C	acceptor_gain	1.0000
8:65724349:CATC:C	acceptor_gain	1.0000
8:65724350:ATC:A	acceptor_loss	1.0000
8:65724351:TCTA:T	acceptor_loss	1.0000
8:65724352:C:A	acceptor_loss	1.0000
8:65724352:C:CC	acceptor_gain	1.0000
8:65724353:T:G	acceptor_loss	1.0000
8:65725987:T:TC	acceptor_gain	1.0000
8:65726870:CCTA:C	donor_loss	1.0000
8:65726871:CTA:C	donor_loss	1.0000
8:65726874:C:A	donor_loss	1.0000
8:65726874:CCTG:C	donor_gain	1.0000
8:65726963:TATT:T	acceptor_gain	1.0000
8:65726964:ATT:A	acceptor_gain	1.0000
8:65726965:TT:T	acceptor_gain	1.0000
8:65726966:TCT:T	acceptor_loss	1.0000
8:65726967:C:CC	acceptor_gain	1.0000
8:65726967:CTACA:C	acceptor_loss	1.0000
8:65728386:C:CA	donor_gain	1.0000
8:65734892:TAA:T	acceptor_gain	1.0000
8:65747648:ACAC:A	donor_loss	1.0000
8:65747649:CA:C	donor_loss	1.0000

AlphaMissense

3179 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:65719457:A:G	W428R	1.000
8:65719457:A:T	W428R	1.000
8:65719491:A:C	F416L	1.000
8:65719491:A:T	F416L	1.000
8:65719493:A:G	F416L	1.000
8:65724291:A:G	W376R	1.000
8:65724291:A:T	W376R	1.000
8:65726945:G:C	H284D	1.000
8:65726949:T:A	E282D	1.000
8:65726949:T:G	E282D	1.000
8:65726950:T:A	E282V	1.000
8:65727207:A:G	L264P	1.000
8:65727225:C:T	G258D	1.000
8:65727230:A:C	H256Q	1.000
8:65727230:A:T	H256Q	1.000
8:65727232:G:C	H256D	1.000
8:65727239:A:C	D253E	1.000
8:65727239:A:T	D253E	1.000
8:65727240:T:A	D253V	1.000
8:65727240:T:C	D253G	1.000
8:65727240:T:G	D253A	1.000
8:65734838:C:G	A218P	1.000
8:65734854:A:C	H212Q	1.000
8:65734854:A:T	H212Q	1.000
8:65734856:G:C	H212D	1.000
8:65745446:A:G	W154R	1.000
8:65745446:A:T	W154R	1.000
8:65719388:A:G	W451R	0.999
8:65719388:A:T	W451R	0.999
8:65719492:A:G	F416S	0.999

dbSNP variants (sampled 300 via entrez): RS1000038038 (8:65826072 G>A), RS1000050014 (8:65831328 G>A), RS1000070490 (8:65747028 A>C,G,T), RS1000087034 (8:65825779 G>A), RS1000128510 (8:65798044 A>C,T), RS1000131448 (8:65754997 A>G), RS1000168737 (8:65801237 T>A,C), RS1000188402 (8:65804541 T>A,C), RS1000208572 (8:65729225 G>C), RS1000214232 (8:65807821 A>G), RS1000225923 (8:65754615 C>T), RS1000262914 (8:65756240 G>A), RS1000264033 (8:65800955 A>G,T), RS1000304490 (8:65804115 T>C), RS1000309679 (8:65767218 C>T)

Disease associations

OMIM: gene MIM:171885 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002949_24	Epilepsy and lamotrigine-induced maculopapular eruptions	6.000000e-07
GCST006224_5	Right lateral prefrontal cortical growth	7.000000e-06
GCST009391_429	Metabolite levels	7.000000e-06
GCST009391_777	Metabolite levels	8.000000e-06
GCST009391_821	Metabolite levels	4.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:1001253	maculopapular eruption
EFO:0010384	phosphatidylcholine 38:2 measurement
EFO:0010393	sphingomyelin 18:0 measurement
EFO:0010398	sphingomyelin 24:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111411 (PROTEIN FAMILY), CHEMBL2363066 (PROTEIN FAMILY), CHEMBL3012 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 116,182 (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
CHEMBL932	DIPYRIDAMOLE	4	51,743
CHEMBL192	SILDENAFIL	4	41,819
CHEMBL484785	CRISABOROLE	4	1,482
CHEMBL2180408	JNJ-42396302	1	12
CHEMBL4297384	GSK-356278	1	48

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
BRL50481	Inhibition	6.8	pIC50
crisaborole	Inhibition	6.14	pIC50

Binding affinities (BindingDB)

198 measured of 207 human assays (207 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-(4-amino-2-methoxyphenyl)-3-cyclohexyl-1-methyl-3,5-dihydropyrazolo[4,3-c]pyridin-1-ium-4-one	IC50	1.3 nM	US-8637528: Use of PDE7 inhibitors for the treatment of movement disorders
1-cyclohexyl-3-methyl-N-[6-(2-oxoimidazolidin-1-yl)-3-pyridinyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	2 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-[4-[4-(methylamino)piperidin-1-yl]cyclohexyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	3.1 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
N-[4-(4-acetylpiperazin-1-yl)cyclohexyl]-1-cyclohexyl-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	3.5 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-[4-(3-methyl-2,5-dioxoimidazolidin-1-yl)cyclohexyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	4 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
N-[3-cyano-4-(4-hydroxypiperidin-1-yl)phenyl]-1-cyclohexyl-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	4.5 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-[4-(3-oxopiperazin-1-yl)phenyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	5 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
US8637528, OM056	IC50	5.67 nM	US-8637528: Use of PDE7 inhibitors for the treatment of movement disorders
1-cyclohexyl-3-methyl-N-[4-(3-methyl-2,5-dioxoimidazolidin-1-yl)phenyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	6.1 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-(4-piperazin-1-ylcyclohexyl)thieno[3,2-d]pyrazole-5-carboxamide	IC50	6.5 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[4-[(2,5-dioxoimidazolidin-1-yl)methyl]cyclohexyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	6.5 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
4-[6-(difluoromethoxy)-3-[(3,4-dimethoxyphenyl)methyl]-2,4-dioxo-4a,5,6,7,8,8a-hexahydroquinazolin-1-yl]piperidine-1-carbaldehyde	IC50	6.7 nM	US-8846654: Therapeutic applications in the cardiovascular field of quinazolinedione derivatives
N-[4-(4-aminopiperidin-1-yl)cyclohexyl]-1-cyclohexyl-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	6.8 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
5-[(1-cyclohexyl-3-methylthieno[3,2-d]pyrazole-5-carbonyl)amino]-2-(4-hydroxypiperidin-1-yl)benzoic acid	IC50	7.2 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-[4-(methylcarbamoyl)cyclohexyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	7.8 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[4-(cyclopropylcarbamoyl)cyclohexyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	7.8 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cycloheptyl-3-methyl-N-[4-(4-methylpiperazin-1-yl)phenyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	8 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[4-[4-(dimethylamino)piperidin-1-yl]cyclohexyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	8.6 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[6-(4-hydroxypiperidin-1-yl)-3-pyridinyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	8.7 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[3-fluoro-4-(4-methyl-1,4-diazepan-1-yl)phenyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	8.9 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-[4-(2-oxoimidazolidin-1-yl)cyclohexyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	8.9 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-(4-morpholin-4-ylcyclohexyl)thieno[3,2-d]pyrazole-5-carboxamide	IC50	9 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[4-(1,1-dioxo-1,2-thiazolidin-2-yl)cyclohexyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	9.9 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-(4-piperazin-1-ylphenyl)thieno[3,2-d]pyrazole-5-carboxamide	IC50	10 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-[3-(methylsulfamoyl)phenyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	10 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[3-fluoro-4-(4-methylpiperazin-1-yl)phenyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	10 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
N-[4-[4-[acetyl(methyl)amino]piperidin-1-yl]cyclohexyl]-1-cyclohexyl-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	10 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[4-(4-hydroxypiperidin-1-yl)-3-methylphenyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	11 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
N-[4-(4-acetylpiperazin-1-yl)phenyl]-1-cyclohexyl-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	12 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]cyclohexyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	13 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[(3R)-3-(dimethylcarbamoyl)cyclopentyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	13 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[6-(2-hydroxyethylcarbamoyl)-3-pyridinyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	13 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[4-(dimethylcarbamoyl)phenyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	14 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-[4-(1-methylpiperidin-4-yl)phenyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	14 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[3-fluoro-4-[4-(methylamino)piperidin-1-yl]phenyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	14 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[4-(2,5-dioxopyrrolidin-1-yl)cyclohexyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	14 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
4-[6-(2,2-difluoroethoxy)-3-[(3,4-dimethoxyphenyl)methyl]-2,4-dioxo-4a,5,6,7,8,8a-hexahydroquinazolin-1-yl]piperidine-1-carbaldehyde	IC50	15 nM	US-8846654: Therapeutic applications in the cardiovascular field of quinazolinedione derivatives
1-cyclohexyl-3-methyl-N-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	15 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-[4-(4-methyl-1,4-diazepan-1-yl)cyclohexyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	15 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[4-(4-hydroxypiperidine-1-carbonyl)cyclohexyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	15 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[(3S)-3-[(2,5-dioxoimidazolidin-1-yl)methyl]cyclopentyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	15 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-[4-(2-oxo-1,3-oxazolidin-3-yl)cyclohexyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	15 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-[4-(4-methylpiperazin-1-yl)cyclohexyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	16 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[4-[2-(dimethylamino)ethyl]phenyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	16 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-[4-(4-methylpiperazin-1-yl)phenyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	17 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[1-(dimethylcarbamoyl)piperidin-4-yl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	17 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-[4-(3-methyl-2-oxoimidazolidin-1-yl)cyclohexyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	17 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-N-[2,3-difluoro-4-(4-hydroxypiperidin-1-yl)phenyl]-3-methylthieno[3,2-d]pyrazole-5-carboxamide	IC50	17 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-[4-(4-methyl-2-oxopiperazin-1-yl)cyclohexyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	17 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity
1-cyclohexyl-3-methyl-N-[4-(2-morpholin-4-ylethyl)phenyl]thieno[3,2-d]pyrazole-5-carboxamide	IC50	18 nM	US-8901315: Thienopyrazole derivative having PDE7 inhibitory activity

ChEMBL bioactivities

748 potent at pChembl≥5 of 808 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL5081214
10.00	IC50	0.1	nM	CHEMBL6170526
9.90	IC50	0.1259	nM	CHEMBL5080391
9.80	IC50	0.1585	nM	CHEMBL5087564
9.60	IC50	0.2512	nM	CHEMBL5094110
9.50	IC50	0.3162	nM	CHEMBL5086895
9.50	IC50	0.3162	nM	CHEMBL5076558
9.49	IC50	0.32	nM	CHEMBL3360172
9.17	IC50	0.68	nM	CHEMBL3360170
9.12	IC50	0.76	nM	GSK-356278
9.00	IC50	1	nM	CHEMBL3354181
9.00	IC50	1	nM	CHEMBL5078680
9.00	IC50	1	nM	CHEMBL5088742
9.00	IC50	1	nM	CHEMBL6141776
8.96	IC50	1.1	nM	CHEMBL3360169
8.92	IC50	1.2	nM	CHEMBL3360171
8.89	IC50	1.3	nM	CHEMBL2019020
8.89	IC50	1.3	nM	CHEMBL3924897
8.85	IC50	1.4	nM	CHEMBL3403373
8.82	IC50	1.5	nM	CHEMBL3403371
8.77	IC50	1.7	nM	CHEMBL5180503
8.70	IC50	2	nM	CHEMBL3354179
8.70	IC50	2	nM	CHEMBL3650287
8.68	IC50	2.1	nM	CHEMBL3360167
8.64	IC50	2.3	nM	CHEMBL3354180
8.60	IC50	2.5	nM	CHEMBL5285855
8.57	IC50	2.7	nM	CHEMBL3403372
8.52	IC50	3	nM	CHEMBL2171440
8.52	IC50	3	nM	CHEMBL6166903
8.52	IC50	3	nM	CHEMBL6167008
8.51	IC50	3.1	nM	CHEMBL3650254
8.48	IC50	3.3	nM	CHEMBL3403346
8.46	IC50	3.5	nM	CHEMBL182536
8.46	IC50	3.5	nM	CHEMBL3650259
8.41	IC50	3.9	nM	CHEMBL186868
8.41	IC50	3.9	nM	CHEMBL3360168
8.40	IC50	4	nM	CHEMBL2019104
8.40	IC50	4	nM	CHEMBL184861
8.40	IC50	4	nM	CHEMBL3650301
8.38	IC50	4.2	nM	CHEMBL3354171
8.36	IC50	4.4	nM	CHEMBL3403358
8.35	IC50	4.5	nM	CHEMBL3650322
8.34	IC50	4.6	nM	CHEMBL3403361
8.31	IC50	4.9	nM	CHEMBL3354178
8.30	IC50	5	nM	CHEMBL3354177
8.30	IC50	5	nM	CHEMBL3650313
8.30	IC50	5	nM	CHEMBL6160471
8.29	IC50	5.1	nM	CHEMBL3403367
8.26	IC50	5.5	nM	CHEMBL5625053
8.25	IC50	5.6	nM	CHEMBL3354175

PubChem BioAssay actives

521 with measured affinity, of 1078 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
8-chloro-5-[2-(2H-tetrazol-5-yl)phenoxy]spiro[1,3-dihydroquinazoline-4,1’-cyclohexane]-2-one	2131363: Inhibition of recombinant PDE7A1 (unknown origin) expressed in Escherichia coli BL21 using [3H]cAMP as substrate preincubated for 15 mins followed by compound addition and measured after 1 hr by liquid scintillation method	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]sulfamoyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-[[N-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxycarbonyl]anilino]methyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0001	uM
[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]amino]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0002	uM
1-[3-[3-ethyl-2-[(3-fluoro-4-pyridinyl)amino]-4-oxothieno[3,2-d]pyrimidin-7-yl]piperidine-1-carbonyl]cyclopropane-1-carbonitrile	1176816: Inhibition of PDE7A (unknown origin)	ic50	0.0003	uM
[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]amino]methyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0003	uM
[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 3-[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]sulfamoyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0003	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-[[[2-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-2-oxo-1-phenylethyl]amino]methyl]benzoate	1812119: Inhibition of PDE4 in human U-937 cells assessed as reduction in cAMP level by LANCE cAMP Assay	ic50	0.0003	uM
methyl 3-[3-ethyl-2-[(3-fluoro-4-pyridinyl)amino]-4-oxothieno[3,2-d]pyrimidin-7-yl]piperidine-1-carboxylate	1176816: Inhibition of PDE7A (unknown origin)	ic50	0.0007	uM
5-[5-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-1,3,4-oxadiazol-2-yl]-1-ethyl-N-(oxan-4-yl)pyrazolo[3,4-b]pyridin-4-amine	2131350: Inhibition of PDE7A (unknown origin)	ic50	0.0008	uM
2-(cyclopentylamino)-3-ethyl-7-(6-morpholin-4-yl-3-pyridinyl)thieno[3,2-d]pyrimidin-4-one	1170815: Inhibition of human PDE7A1 expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	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
methyl 4-[3-ethyl-2-[(3-fluoro-4-pyridinyl)amino]-4-oxothieno[3,2-d]pyrimidin-7-yl]piperidine-1-carboxylate	1176816: Inhibition of PDE7A (unknown origin)	ic50	0.0011	uM
3-ethyl-2-[(3-fluoro-4-pyridinyl)amino]-7-[1-(3-hydroxy-2,2-dimethylpropanoyl)piperidin-3-yl]thieno[3,2-d]pyrimidin-4-one	1176816: Inhibition of PDE7A (unknown origin)	ic50	0.0012	uM
6-(4-amino-2-methoxyphenyl)-3-cyclohexyl-1-methyl-5H-pyrazolo[5,4-d]pyrimidin-4-one	657347: Displacement of [3H]-cAMP from human recombinant PDE7A	ic50	0.0013	uM
3-ethyl-7-[1-(3-methylpyridine-2-carbonyl)pyrrolidin-3-yl]-2-(propan-2-ylamino)thieno[3,2-d]pyrimidin-4-one	1195093: Inhibition of human PDE7A expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0014	uM
7-(1-benzoylpyrrolidin-3-yl)-3-ethyl-2-(propan-2-ylamino)thieno[3,2-d]pyrimidin-4-one	1195093: Inhibition of human PDE7A expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0015	uM
8-chloro-5-[(2-(111C)methyltetrazol-5-yl)methoxy]spiro[1,3-dihydroquinazoline-4,1’-cyclohexane]-2-one	1924461: Inhibition of PDE7 (unknown origin)	ic50	0.0017	uM
2-(cyclopentylamino)-3-ethyl-7-pyridin-3-ylthieno[3,2-d]pyrimidin-4-one	1170815: Inhibition of human PDE7A1 expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0020	uM
3-ethyl-2-[(3-fluoro-4-pyridinyl)amino]-7-(2-hydroxypropan-2-yl)thieno[3,2-d]pyrimidin-4-one	1176816: Inhibition of PDE7A (unknown origin)	ic50	0.0021	uM
2-(cyclopentylamino)-3-ethyl-7-[4-(morpholin-4-ylmethyl)phenyl]thieno[3,2-d]pyrimidin-4-one	1170815: Inhibition of human PDE7A1 expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0023	uM
3-ethyl-2-(propan-2-ylamino)-7-[1-(pyridine-2-carbonyl)pyrrolidin-3-yl]thieno[3,2-d]pyrimidin-4-one	1195093: Inhibition of human PDE7A expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0027	uM
2-[4-(5-cyclohexyl-7-methyl-4-oxo-3H-imidazo[4,5-d]pyridazin-2-yl)-3-methoxyphenyl]cyclopropane-1-carboxamide	702754: Inhibition of cloned human recombinant PDE7A assessed as [3H]cAMP hydrolysis by radiometric assay	ic50	0.0030	uM
3-ethyl-7-[1-(6-methylpyridine-2-carbonyl)pyrrolidin-3-yl]-2-(propan-2-ylamino)thieno[3,2-d]pyrimidin-4-one	1195093: Inhibition of human PDE7A expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0033	uM
3-[(8-chloro-2-oxospiro[1,3-dihydroquinazoline-4,1’-cyclohexane]-5-yl)oxymethyl]-4H-1,2,4-oxadiazol-5-one	242246: Inhibition of human PDE7A1 expressed in baculovirus infected Sf9 cells	ic50	0.0035	uM
3-ethyl-2-[(3-fluoro-4-pyridinyl)amino]-7-(3-hydroxypropyl)thieno[3,2-d]pyrimidin-4-one	1176816: Inhibition of PDE7A (unknown origin)	ic50	0.0039	uM
7-(5-cyclohexylimino-4-methyl-1,3,4-thiadiazol-2-yl)-2-methylquinazolin-4-amine	242457: Inhibition of human Phosphodiesterase 7A1 expressed in baculovirus infected Sf9 cells	ic50	0.0039	uM
3-cyclohexyl-6-[4-(1,4-diazepan-1-yl)-2-methoxyphenyl]-5H-[1,2]thiazolo[5,4-d]pyrimidin-4-one	657347: Displacement of [3H]-cAMP from human recombinant PDE7A	ic50	0.0040	uM
8-chloro-5-(2H-tetrazol-5-ylmethoxy)spiro[1,3-dihydroquinazoline-4,1’-cyclohexane]-2-one	242246: Inhibition of human PDE7A1 expressed in baculovirus infected Sf9 cells	ic50	0.0040	uM
2-(cyclopentylamino)-3-ethyl-7-(2-pyridin-3-ylethynyl)thieno[3,2-d]pyrimidin-4-one	1170815: Inhibition of human PDE7A1 expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0042	uM
3-ethyl-2-(propan-2-ylamino)-7-pyridin-3-ylthieno[3,2-d]pyrimidin-4-one	1195093: Inhibition of human PDE7A expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0044	uM
3-ethyl-7-(2-methoxy-4-pyridinyl)-2-(propan-2-ylamino)thieno[3,2-d]pyrimidin-4-one	1195093: Inhibition of human PDE7A expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0046	uM
methyl 4-[2-(cyclopentylamino)-3-ethyl-4-oxothieno[3,2-d]pyrimidin-7-yl]benzoate	1170815: Inhibition of human PDE7A1 expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0049	uM
methyl 3-[2-(cyclopentylamino)-3-ethyl-4-oxothieno[3,2-d]pyrimidin-7-yl]benzoate	1170815: Inhibition of human PDE7A1 expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0050	uM
7-(1-acetylpiperidin-3-yl)-3-ethyl-2-(propan-2-ylamino)thieno[3,2-d]pyrimidin-4-one	1195093: Inhibition of human PDE7A expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0051	uM
2-[3-[(3,4-dimethoxyphenyl)methyl]-2,4-dioxo-1-(thian-4-yl)quinazolin-6-yl]oxyacetonitrile	2131351: Inhibition of full length PDE7 (unknown origin) using FAM-cAMP as substrate by fluorescence based analysis	ic50	0.0055	uM
2-(cyclopentylamino)-3-ethyl-7-phenylthieno[3,2-d]pyrimidin-4-one	1170815: Inhibition of human PDE7A1 expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0056	uM
2-[3-[(3,4-dimethoxyphenyl)methyl]-2,4-dioxo-1-(1-oxothian-4-yl)quinazolin-6-yl]oxyacetonitrile	2131351: Inhibition of full length PDE7 (unknown origin) using FAM-cAMP as substrate by fluorescence based analysis	ic50	0.0061	uM
7-(2,4-dimethyl-1,3-thiazol-5-yl)-3-ethyl-2-(propan-2-ylamino)thieno[3,2-d]pyrimidin-4-one	1195093: Inhibition of human PDE7A expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0064	uM
3-ethyl-2-(propan-2-ylamino)-7-(1-pyridin-2-ylpiperidin-4-yl)thieno[3,2-d]pyrimidin-4-one	1195093: Inhibition of human PDE7A expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0068	uM
3-cyclohexyl-6-[4-(4-hydroxyazepan-1-yl)-2-methoxyphenyl]-5H-[1,2]thiazolo[5,4-d]pyrimidin-4-one	657347: Displacement of [3H]-cAMP from human recombinant PDE7A	ic50	0.0070	uM
2-(cyclopentylamino)-3-ethyl-7-(2-pyridin-3-ylethyl)thieno[3,2-d]pyrimidin-4-one	1170815: Inhibition of human PDE7A1 expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0073	uM
3-ethyl-2-(propan-2-ylamino)-7-pyrimidin-5-ylthieno[3,2-d]pyrimidin-4-one	1195093: Inhibition of human PDE7A expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0076	uM
6-[4-(4-aminopiperidin-1-yl)-2-methoxyphenyl]-3-cyclohexyl-5H-[1,2]thiazolo[5,4-d]pyrimidin-4-one	657347: Displacement of [3H]-cAMP from human recombinant PDE7A	ic50	0.0080	uM
3-ethyl-7-[1-(3-methylbutanoyl)pyrrolidin-3-yl]-2-(propan-2-ylamino)thieno[3,2-d]pyrimidin-4-one	1195093: Inhibition of human PDE7A expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0081	uM
3-ethyl-7-[1-(2-methylpropanoyl)pyrrolidin-3-yl]-2-(propan-2-ylamino)thieno[3,2-d]pyrimidin-4-one	1195093: Inhibition of human PDE7A expressed in insect cells assessed as inhibition of [3H]cAMP to [3H]AMP hydrolysis after 30 mins by scintillation counting	ic50	0.0084	uM
3-ethyl-2-[(3-fluoro-4-pyridinyl)amino]-7-(1-hydroxyethyl)thieno[3,2-d]pyrimidin-4-one	1176816: Inhibition of PDE7A (unknown origin)	ic50	0.0087	uM
3-cyclohexyl-6-(2-methoxy-4-piperazin-1-ylphenyl)-5H-[1,2]thiazolo[5,4-d]pyrimidin-4-one	657347: Displacement of [3H]-cAMP from human recombinant PDE7A	ic50	0.0090	uM
5-[(8-chloro-2-oxospiro[1,3-dihydroquinazoline-4,1’-cyclohexane]-5-yl)oxymethyl]furan-2-carboxylic acid	242246: Inhibition of human PDE7A1 expressed in baculovirus infected Sf9 cells	ic50	0.0100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	6
methylmercuric chloride	decreases expression, increases expression	2
trichostatin A	decreases expression, affects cotreatment	2
Cyclic AMP	decreases reaction, increases hydrolysis	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Particulate Matter	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol A	decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects expression	1
methylparaben	increases expression	1
cobaltous chloride	affects cotreatment, increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
lead chloride	affects cotreatment, increases expression	1
trequinsin	decreases activity	1
cadmium sulfate	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
CGP 52608	increases reaction, affects binding	1
SCH 51866	decreases reaction, increases hydrolysis	1
Roflumilast	decreases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
L-826,141	decreases activity	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Bortezomib	decreases expression	1

ChEMBL screening assays

197 unique, capped per target: 189 binding, 6 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1943244	Binding	Inhibition of recombinant human PDE7 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
CHEMBL4348842	ADMET	Inhibition of PDE7 (unknown origin)	Structure Overhaul Affords a Potent Purine PI3Kδ Inhibitor with Improved Tolerability. — J Med Chem
CHEMBL858855	Functional	Inhibition of PDE7 in HuT78 cells at 100 uM	First dual M3 antagonists-PDE4 inhibitors: synthesis and SAR of 4,6-diaminopyrimidine derivatives. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TC69	HAP1 PDE7A (-) 1	Cancer cell line	Male
CVCL_TC70	HAP1 PDE7A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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