PDE5A

Summary

PDE5A (phosphodiesterase 5A, HGNC:8784) is a protein-coding gene on chromosome 4q26, encoding cGMP-specific 3’,5’-cyclic phosphodiesterase (O76074). Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides.

This gene encodes a cGMP-binding, cGMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family. This phosphodiesterase specifically hydrolyzes cGMP to 5’-GMP. It is involved in the regulation of intracellular concentrations of cyclic nucleotides and is important for smooth muscle relaxation in the cardiovascular system. Alternative splicing of this gene results in three transcript variants encoding distinct isoforms.

Source: NCBI Gene 8654 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 132 total
• Druggable target: yes — 30 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001083

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8784
Approved symbol	PDE5A
Name	phosphodiesterase 5A
Location	4q26
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000138735
Ensembl biotype	protein_coding
OMIM	603310
Entrez	8654

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000264805, ENST00000354960, ENST00000394439, ENST00000420633, ENST00000502912, ENST00000503412, ENST00000508914, ENST00000509612, ENST00000512450, ENST00000512494, ENST00000512739, ENST00000513594, ENST00000925607, ENST00000925608

RefSeq mRNA: 3 — MANE Select: NM_001083 NM_001083, NM_033430, NM_033437

CCDS: CCDS34055, CCDS3713

Canonical transcript exons

ENST00000354960 — 21 exons

Exon	Start	End
ENSE00000935544	119596523	119596612
ENSE00000970323	119567073	119567144
ENSE00000970324	119565321	119565410
ENSE00000970325	119562833	119562970
ENSE00000970328	119552550	119552637
ENSE00001016840	119507604	119507704
ENSE00001016841	119502581	119502655
ENSE00001016845	119501170	119501253
ENSE00001016847	119505855	119505932
ENSE00001851914	119628520	119628804
ENSE00001890486	119494403	119498738
ENSE00003460007	119520935	119521060
ENSE00003462098	119525549	119525695
ENSE00003536164	119504536	119504599
ENSE00003537282	119542459	119542634
ENSE00003557390	119560296	119560363
ENSE00003566974	119538960	119539019
ENSE00003574404	119519045	119519139
ENSE00003630080	119511047	119511134
ENSE00003641439	119553638	119553746
ENSE00003651847	119606709	119607297

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 97.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.6332 / max 264.5648, expressed in 1112 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53773	1.8396	556
53776	1.3340	608
53763	1.1194	438
53771	0.8868	329
53769	0.6007	237
53766	0.4675	205
53764	0.3289	164
53767	0.3058	150
53770	0.3050	156
53774	0.2180	109

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.81	gold quality
descending thoracic aorta	UBERON:0002345	96.63	gold quality
colonic epithelium	UBERON:0000397	96.21	gold quality
thoracic aorta	UBERON:0001515	96.10	gold quality
cauda epididymis	UBERON:0004360	96.09	gold quality
ascending aorta	UBERON:0001496	96.05	gold quality
right coronary artery	UBERON:0001625	95.98	gold quality
aorta	UBERON:0000947	95.90	gold quality
popliteal artery	UBERON:0002250	95.79	gold quality
tibial artery	UBERON:0007610	95.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.49	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.45	gold quality
lower esophagus	UBERON:0013473	95.44	gold quality
mucosa of stomach	UBERON:0001199	95.39	gold quality
artery	UBERON:0001637	95.36	gold quality
caput epididymis	UBERON:0004358	94.83	gold quality
rectum	UBERON:0001052	94.33	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.31	gold quality
left coronary artery	UBERON:0001626	93.51	gold quality
corpus epididymis	UBERON:0004359	93.15	gold quality
visceral pleura	UBERON:0002401	92.59	gold quality
right uterine tube	UBERON:0001302	92.52	gold quality
coronary artery	UBERON:0001621	92.51	gold quality
urethra	UBERON:0000057	92.32	gold quality
sigmoid colon	UBERON:0001159	91.90	gold quality
seminal vesicle	UBERON:0000998	91.59	gold quality
endocervix	UBERON:0000458	91.40	gold quality
superficial temporal artery	UBERON:0001614	91.40	gold quality
sural nerve	UBERON:0015488	91.40	gold quality
right lung	UBERON:0002167	91.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): POU3F2

miRNA regulators (miRDB)

247 targeting PDE5A, 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-4262	100.00	73.26	3931
HSA-MIR-1277-5P	100.00	73.95	5056
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-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-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4500	99.99	72.72	2367

Literature-anchored findings (GeneRIF, showing 40)

• Human PDE5A gene encodes three PDE5 isoforms from two alternate promoters. (PMID:11896473)
• cGMP-directed regulation of PDE5 phosphorylation and the resulting increase in cGMP binding affinity occur largely within the R domain (PMID:12359732)
• CGMP-dependent protein kinase I causes NO-induced PDE5 phosphorylation. However, cGMP can directly activate PDE5 without phosphorylation in platelet cytosol, most likely by binding to GAF domains. (PMID:12604588)
• GAFa domain of PDE5A adopts a structure similar to the GAFb domain of PDE2A, and provides the sole site for cGMP binding in PDE5A (PMID:12650945)
• three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra) (PMID:12955149)
• Crystal structures of phosphodiesterases 4 and 5 in complex with inhibitor 3-isobutyl-1-methylxanthine (PMID:14668322)
• demonstrated, for the first time, that androgens positively regulate phosphodiesterase 5 (PMID:14764637)
• no correlations of a novel polymorphism of the PDE5A promoter gene with the intermediate phenotype essential hypertension/erectile dysfunction (PMID:15175637)
• Phosphorylation of PDE5 seems to act as memory switch for activation leading to long-term desensitization of the signaling pathway. (PMID:15240816)
• PDE5 gene expression and activity are androgen-dependent in vas deferens. (PMID:15640438)
• Phosphodiesterase Type 5 is the main factor regulating cyclic guanosine monophosphate hydrolysis and downstream signaling in human PASMCs. (PMID:15817798)
• Results suggest that glutamine(817) is a positive determinant for phosphodiesterase 5 affinity for cyclic GMP and several inhibitors. (PMID:16407275)
• Subdomains are structurally and functionally interdependent and act in concert in regulating human PDE5. (PMID:16690614)
• Virtually all tissues and cell types express PDE5, with heart and cardiomyocytes being contentious; PDE5A1 and PDE5A2 are ubiquitous, but PDE5A3 is specific to smooth muscle, as described in this review. (PMID:17017938)
• PDE5 may be a possible therapeutic target in bladder dysfunction for ameliorating irritative lower urinary tract symptoms. (PMID:17138653)
• The PDE-5A was expressed in both pre-adipocytes and adipocytes. PDE-5A mRNA and protein levels decreased as pre-adipocytes differentiated. (PMID:17906676)
• GAF domains of PDE5A can act as sensors and intracellular sinks for cyclic GMP, but not cyclic AMP. (PMID:18293931)
• analysis of functional chimeras of the phosphodiesterase 5 and 10 tandem GAF domains (PMID:18635550)
• may define a molecular mechanism by which PDE5 inhibition can differentially impact selected cellular functions of platelets, and perhaps of other cell types (PMID:18757735)
• Increased myocardial PDE5 expression in patients with advanced cardiomyopathy may contribute to the development of heart failure and represents an important therapeutic target. (PMID:19139381)
• The rAd5-shRNA-PDE5A3 can obviously increase the cGMP level in the smooth muscle cells of human corpus cavernosum, and enhance the inhibition of the PDE5 gene. (PMID:19852267)
• PDE5-inhibition blocks TRPC6 channel activation and associated Cn/NFAT activation signaling by PKG-dependent channel phosphorylation (PMID:19961855)
• Data show that SS increased intracellular cGMP levels and activated protein kinase G, and selectively inhibited PDE5 in breast tumor cells. (PMID:19996273)
• The distribution of PDE-5 and NOD II may indicate a physiologic role in the regulatory function of human vagina. (PMID:20177899)
• Data show that the identified compound will be a useful agent for evaluating the therapeutic potential of central inhibition of PDE5. (PMID:20196613)
• Myocardial oxidative stress increases PDE5 expression in the failing heart (PMID:20308615)
• High PDE5A1 expression is associated with malignant melanoma. (PMID:20332439)
• Suggest that PDE5A is associated with increased disease susceptibility, pathological progression, and development of proteinuria in childhood IgA nephropathy. (PMID:20563733)
• Conformation changes, N-terminal involvement, and cGMP signal relay in the phosphodiesterase-5 GAF domain. (PMID:20861010)
• Distinct allostery induced in the cyclic GMP-binding, cyclic GMP-specific phosphodiesterase (PDE5) by cyclic GMP, sildenafil, and metal ions. (PMID:21193396)
• In melanoma cells, oncogenic (V600E) BRAF signaling downregulates PDE5A through the transcription factor BRN2, leading to increased cGMP and Ca2+ and the induction of invasion through increased cell contractility. (PMID:21215707)
• the spatial localization of PDE5A at the level of caveolin-rich lipid rafts allows for a feedback loop between endothelial PDE5A and nitric oxide synthase (NOS3) (PMID:21421555)
• Solved is the crystal structure of the structurally uncharacterized PDE5A GAF-B domain. (PMID:21425347)
• PDE5 inhibition by sulindac sulfide selectively induces apoptosis and attenuates oncogenic Wnt/beta-catenin-mediated transcription in human breast tumor cells (PMID:21505183)
• These studies suggest a novel role for PDE5 in erythrocytes. (PMID:21525805)
• found in smooth muscle wall of blood vessels transversing the clitoral supepithelial and stromal space (PMID:21697861)
• 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)
• Treatment of L-1236 with PDE5A-inhibitor sildenafil or with siRNA directed against PDE5A and concomitant stimulation with cyclic guanosine monophosphate (cGMP) resulted in enhanced apoptosis, indicating PDE5A as an oncogene. (PMID:21987443)
• PDE5 is highly expressed and increases ( approximately 130%) during growth whereas ABCC5 exhibited low to moderate expression, with a moderate increase ( approximately 40%) during growth (PMID:22843873)
• 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)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	pde5ab	ENSDARG00000051915
mus_musculus	Pde5a	ENSMUSG00000053965
rattus_norvegicus	Pde5a	ENSRNOG00000014443
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), PDE3B (ENSG00000152270), PDE1C (ENSG00000154678), PDE9A (ENSG00000160191), PDE7B (ENSG00000171408), PDE3A (ENSG00000172572), PDE4B (ENSG00000184588), PDE2A (ENSG00000186642), PDE7A (ENSG00000205268)

Protein

Protein identifiers

cGMP-specific 3’,5’-cyclic phosphodiesterase — O76074 (reviewed: O76074)

Alternative names: cGMP-binding cGMP-specific phosphodiesterase

All UniProt accessions (4): O76074, C9JGT3, G5E9C5, H0YA14

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5’-GMP. Specifically regulates nitric-oxide-generated cGMP.

Tissue specificity. Expressed in aortic smooth muscle cells, heart, placenta, skeletal muscle and pancreas and, to a much lesser extent, in brain, liver and lung.

Post-translational modifications. Phosphorylation is regulated by binding of cGMP to the two allosteric sites. Phosphorylation by PRKG1 leads to its activation.

Activity regulation. Sildenafil (Viagra) is a highly selective and potent inhibitor of PDE5A and is effective in the treatment of penile erectile dysfunction. Also inhibited by zaprinast.

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.

Domain organisation. Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain which contains two homologous allosteric cGMP-binding regions, A and B.

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

Similarity. Belongs to the cyclic nucleotide phosphodiesterase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O76074-1	PDE5A1	yes
O76074-2	PDE5A2

RefSeq proteins (3): NP_001074, NP_236914, NP_246273 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002073	PDEase_catalytic_dom	Domain
IPR003018	GAF	Domain
IPR003607	HD/PDEase_dom	Domain
IPR023088	PDEase	Family
IPR023174	PDEase_CS	Conserved_site
IPR029016	GAF-like_dom_sf	Homologous_superfamily
IPR036971	PDEase_catalytic_dom_sf	Homologous_superfamily

Pfam: PF00233, PF01590

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 (92 total): helix 34, strand 21, turn 10, binding site 6, sequence conflict 5, domain 3, mutagenesis site 3, sequence variant 2, region of interest 2, compositionally biased region 2, chain 1, modified residue 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

50 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1TBF	X-RAY DIFFRACTION	1.3
1XOZ	X-RAY DIFFRACTION	1.37
5JO3	X-RAY DIFFRACTION	1.49
2CHM	X-RAY DIFFRACTION	1.6
1XP0	X-RAY DIFFRACTION	1.79
3HC8	X-RAY DIFFRACTION	1.79
2H44	X-RAY DIFFRACTION	1.8
3HDZ	X-RAY DIFFRACTION	1.8
8W4S	X-RAY DIFFRACTION	1.85
2H40	X-RAY DIFFRACTION	1.85
3TGG	X-RAY DIFFRACTION	1.91
6L6E	X-RAY DIFFRACTION	1.92
3SIE	X-RAY DIFFRACTION	1.93
3TGE	X-RAY DIFFRACTION	1.96
1T9S	X-RAY DIFFRACTION	2
3BJC	X-RAY DIFFRACTION	2
4MD6	X-RAY DIFFRACTION	2
1RKP	X-RAY DIFFRACTION	2.05
3B2R	X-RAY DIFFRACTION	2.07
4I9Z	X-RAY DIFFRACTION	2.08
1T9R	X-RAY DIFFRACTION	2.1
4OEX	X-RAY DIFFRACTION	2.14
6IWI	X-RAY DIFFRACTION	2.15
4IA0	X-RAY DIFFRACTION	2.17
8W4T	X-RAY DIFFRACTION	2.2
7FAQ	X-RAY DIFFRACTION	2.2
4G2W	X-RAY DIFFRACTION	2.28
1UDT	X-RAY DIFFRACTION	2.3
2H42	X-RAY DIFFRACTION	2.3
6VBI	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76074-F1	82.32	0.46

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): 613 (proton donor)

Ligand- & substrate-binding residues (6): 653; 654; 654; 764; 817; 617

Post-translational modifications (1): 102

Mutagenesis-validated functional residues (3):

Position	Phenotype
767	changes substrate selectivity from cgmp-specific to dual camp and cgmp binding and hydrolysis; when associated with y-77
775	changes substrate selectivity from cgmp-specific to dual camp and cgmp binding and hydrolysis; when associated with n-76
853	changes substrate selectivity from cgmp-specific to dual camp and cgmp binding and hydrolysis; when associated with n-76

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-418457	cGMP effects
R-HSA-445355	Smooth Muscle Contraction
R-HSA-9013422	RHOBTB1 GTPase cycle

MSigDB gene sets: 199 (showing top): GGTGTGT_MIR329, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, MODULE_65, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CYCLIC_NUCLEOTIDE_METABOLIC_PROCESS, CHANDRAN_METASTASIS_DN, GOBP_CYCLIC_NUCLEOTIDE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GTGCCTT_MIR506, BROWNE_HCMV_INFECTION_14HR_DN, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN

GO Biological Process (3): signal transduction (GO:0007165), cGMP catabolic process (GO:0046069), negative regulation of cAMP/PKA signal transduction (GO:0141162)

GO Molecular Function (10): 3’,5’-cyclic-nucleotide phosphodiesterase activity (GO:0004114), 3’,5’-cyclic-AMP phosphodiesterase activity (GO:0004115), cGMP binding (GO:0030553), metal ion binding (GO:0046872), 3’,5’-cyclic-GMP phosphodiesterase activity (GO:0047555), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Nitric oxide stimulates guanylate cyclase	1
Muscle contraction	1
RHOBTB GTPase Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
3’,5’-cyclic-nucleotide phosphodiesterase activity	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
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
cyclic-nucleotide phosphodiesterase activity	1
cyclic nucleotide binding	1
guanyl ribonucleotide binding	1
anion binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
phosphoric ester hydrolase activity	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1368 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE5A	ALDH7A1	P49419	946
PDE5A	PRKG1	P14619	780
PDE5A	MAPK3	P27361	680
PDE5A	NOS3	P29474	664
PDE5A	PRKACB	P22694	661
PDE5A	ITPR1	Q14643	636
PDE5A	NOS1	P29475	630
PDE5A	EDN1	P05305	629
PDE5A	PDE4A	P27815	624
PDE5A	NPPA	P01160	616
PDE5A	IRAG1	Q9Y6F6	607
PDE5A	SEPTIN8	Q92599	604
PDE5A	SEPTIN3	Q9UH03	601
PDE5A	EDNRA	P25101	572
PDE5A	ACE	P12821	571

IntAct

23 interactions, top by confidence:

A	B	Type	Score
AIPL1	PDE5A	psi-mi:“MI:0914”(association)	0.640
PDE5A	SPG21	psi-mi:“MI:0915”(physical association)	0.560
AIPL1	SUPT5H	psi-mi:“MI:0914”(association)	0.510
PRKG1	PDE5A	psi-mi:“MI:0914”(association)	0.500
PDE5A	PRKG1	psi-mi:“MI:0914”(association)	0.500
PDE5A	PRKG1	psi-mi:“MI:0915”(physical association)	0.500
PDE5A	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
ITPR1	PDE5A	psi-mi:“MI:0914”(association)	0.350
PPP1CA	ACO2	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
MSH5	GET1	psi-mi:“MI:0914”(association)	0.350
SUPT5H	PDE5A	psi-mi:“MI:0915”(physical association)	0.000
CEP43	PDE5A	psi-mi:“MI:0915”(physical association)	0.000
BLM	PDE5A	psi-mi:“MI:0915”(physical association)	0.000
FKBP15	PDE5A	psi-mi:“MI:0915”(physical association)	0.000
PATZ1	PDE5A	psi-mi:“MI:0915”(physical association)	0.000
MIOS	PDE5A	psi-mi:“MI:0915”(physical association)	0.000
PDE5A	WDR24	psi-mi:“MI:0915”(physical association)	0.000
PDE5A	AIPL1	psi-mi:“MI:0915”(physical association)	0.000
SPG21	PDE5A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): AIPL1 (Affinity Capture-MS), PDE5A (Affinity Capture-MS), PDE5A (Affinity Capture-MS), PDE5A (Affinity Capture-MS), PDE5A (Affinity Capture-MS), WDR24 (Affinity Capture-MS), PDE5A (Affinity Capture-MS), PDE5A (Affinity Capture-MS), PDE5A (Affinity Capture-Western), RHOBTB1 (Affinity Capture-Western), PDE5A (Two-hybrid), HIST1H2BH (Proximity Label-MS), PDE5A (Affinity Capture-RNA), PDE5A (Affinity Capture-MS), PDE5A (Affinity Capture-MS)

ESM2 similar proteins: A0A4X1T4U3, A4IFD0, F1QWA8, O02697, O14829, O14830, O14936, O35099, O35385, O35655, O60308, O70589, O76074, O77746, P26045, P33402, P48736, Q21029, Q28156, Q32M07, Q3SWT6, Q3USB7, Q3UYK3, Q3V3E1, Q4R3W4, Q502L7, Q5M7G4, Q5VRN0, Q62688, Q62915, Q68FP8, Q6AZT7, Q6P618, Q6ZT07, Q8BGG7, Q8BTI9, Q8CG03, Q8TEU7, Q8TF42, Q8VDY4

Diamond homologs: B3LVW5, B3P3K2, B4G4E5, B4HEM4, B4JXX2, B4K9L4, B4LVU6, B4NAL6, B4PSS5, B4QZU1, B7YZV4, H2QL32, O00408, O54735, O70628, O76074, O76083, O77746, O89084, P0C1Q2, P11541, P14099, P14100, P14644, P14646, P16499, P16586, P23439, P23440, P27664, P27815, P30645, P33726, P35913, P51160, P52731, P54748, P54750, P91119, Q01061

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
icariin	down-regulates	PDE5A	“chemical inhibition”
tadalafil	“down-regulates activity”	PDE5A	“chemical inhibition”
RHOBTB1	“down-regulates quantity by destabilization”	PDE5A	binding
“Cullin 3-RBX1-Skp1”	“down-regulates quantity by destabilization”	PDE5A	polyubiquitination
sildenafil	“down-regulates activity”	PDE5A	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	10
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

3502 predictions. Top by Δscore:

Variant	Effect	Δscore
4:119498577:TCA:T	donor_gain	1.0000
4:119498603:AGTT:A	donor_gain	1.0000
4:119502576:CT:C	donor_loss	1.0000
4:119502577:TT:T	donor_loss	1.0000
4:119502578:TACAG:T	donor_loss	1.0000
4:119502579:A:AC	donor_gain	1.0000
4:119502579:A:T	donor_loss	1.0000
4:119502580:C:A	donor_loss	1.0000
4:119502580:C:CG	donor_gain	1.0000
4:119502580:CA:C	donor_gain	1.0000
4:119502580:CAG:C	donor_gain	1.0000
4:119502580:CAGT:C	donor_gain	1.0000
4:119502580:CAGTG:C	donor_gain	1.0000
4:119502654:ATCTG:A	acceptor_loss	1.0000
4:119502655:TCTGA:T	acceptor_loss	1.0000
4:119502656:C:CC	acceptor_gain	1.0000
4:119502657:T:A	acceptor_loss	1.0000
4:119505849:A:AC	donor_gain	1.0000
4:119505850:C:CC	donor_gain	1.0000
4:119505850:CTTA:C	donor_gain	1.0000
4:119505851:TTACA:T	donor_loss	1.0000
4:119505853:A:AC	donor_gain	1.0000
4:119505853:ACAA:A	donor_loss	1.0000
4:119505854:C:CA	donor_gain	1.0000
4:119505854:CA:C	donor_gain	1.0000
4:119505854:CAA:C	donor_gain	1.0000
4:119505854:CAAA:C	donor_gain	1.0000
4:119505854:CAAAA:C	donor_gain	1.0000
4:119505865:C:CA	donor_gain	1.0000
4:119507602:A:AC	donor_gain	1.0000

AlphaMissense

5871 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:119498672:A:G	W853R	1.000
4:119498672:A:T	W853R	1.000
4:119501200:G:C	F820L	1.000
4:119501200:G:T	F820L	1.000
4:119501202:A:G	F820L	1.000
4:119502629:A:C	F786L	1.000
4:119502629:A:T	F786L	1.000
4:119502631:A:G	F786L	1.000
4:119504576:T:A	D764V	1.000
4:119504576:T:G	D764A	1.000
4:119519084:T:A	D654V	1.000
4:119519084:T:G	D654A	1.000
4:119521048:A:G	W598R	1.000
4:119521048:A:T	W598R	1.000
4:119562957:A:G	L336P	1.000
4:119562963:A:G	L334P	1.000
4:119562966:A:G	L333P	1.000
4:119565365:C:G	A317P	1.000
4:119565373:A:G	L314P	1.000
4:119567131:G:T	A282D	1.000
4:119567137:C:T	G280D	1.000
4:119596542:A:T	I271N	1.000
4:119596550:A:C	C268W	1.000
4:119596554:A:G	L267P	1.000
4:119596601:G:C	F251L	1.000
4:119596601:G:T	F251L	1.000
4:119596602:A:G	F251S	1.000
4:119596603:A:G	F251L	1.000
4:119606758:C:T	G231E	1.000
4:119606890:A:G	L187P	1.000

dbSNP variants (sampled 300 via entrez): RS1000017588 (4:119621248 T>C), RS1000035055 (4:119590029 T>C), RS1000047520 (4:119538453 A>T), RS1000047978 (4:119569900 C>G,T), RS1000060342 (4:119586746 AAATGT>A), RS1000093386 (4:119538142 C>A,T), RS1000109247 (4:119503747 C>G), RS1000123720 (4:119614551 C>A,T), RS1000159070 (4:119610396 T>A,C), RS1000167094 (4:119507476 C>A,G,T), RS1000208636 (4:119627365 G>A), RS1000226385 (4:119617738 T>C), RS1000240550 (4:119528528 G>C), RS1000246109 (4:119567862 C>T), RS1000258965 (4:119617433 T>C)

Disease associations

OMIM: gene MIM:603310 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST004280_86	Diastolic blood pressure	3.000000e-15
GCST004603_271	Platelet count	3.000000e-09
GCST004607_225	Plateletcrit	6.000000e-10
GCST004787_33	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	1.000000e-08
GCST007094_199	Diastolic blood pressure	9.000000e-19
GCST007099_258	Systolic blood pressure	2.000000e-08
GCST007483_1	Waist-to-hip ratio adjusted for BMI (additive genetic model)	3.000000e-08
GCST007487_52	Waist-to-hip ratio adjusted for BMI (additive genetic model)	1.000000e-09
GCST007500_30	Waist-to-hip ratio adjusted for BMI (additive genetic model)	5.000000e-09
GCST007502_40	Waist-to-hip ratio adjusted for BMI (additive genetic model)	5.000000e-09
GCST008163_496	Height	1.000000e-06
GCST008363_108	Offspring birth weight	9.000000e-09
GCST010002_14	Refractive error	5.000000e-18
GCST010479_69	Coronary artery disease	2.000000e-08
GCST90020024_678	A body shape index	2.000000e-13
GCST90020024_679	A body shape index	2.000000e-08
GCST90020025_611	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020027_1838	Waist-hip index	2.000000e-08
GCST90020029_753	Waist circumference adjusted for body mass index	1.000000e-08
GCST90020029_754	Waist circumference adjusted for body mass index	2.000000e-14

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0006335	systolic blood pressure
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (8): CHEMBL1827 (SINGLE PROTEIN), CHEMBL2095220 (SELECTIVITY GROUP), CHEMBL2097161 (PROTEIN FAMILY), CHEMBL2111340 (SELECTIVITY GROUP), CHEMBL2111400 (SELECTIVITY GROUP), CHEMBL2111470 (SELECTIVITY GROUP), CHEMBL2363066 (PROTEIN FAMILY), CHEMBL4523626 (CHIMERIC PROTEIN)

Molecules with ChEMBL bioactivity

30 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 429,066 (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
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1339	VARDENAFIL HYDROCHLORIDE	4	124
CHEMBL1520	VARDENAFIL	4	21,078
CHEMBL1737	SILDENAFIL CITRATE	4	16,350
CHEMBL189	MILRINONE	4	20,605
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL192	SILDENAFIL	4	41,819
CHEMBL19449	IBUDILAST	4	7,461
CHEMBL1963681	AVANAFIL	4	4,891
CHEMBL502	DONEPEZIL	4	43,493
CHEMBL506247	TANNIC ACID	4	25,753
CHEMBL779	TADALAFIL	4	23,417
CHEMBL932	DIPYRIDAMOLE	4	51,743
CHEMBL19224	PAPAVERINE	3	22,172
CHEMBL2103849	UDENAFIL	3	962
CHEMBL498485	ICARITIN	3	700
CHEMBL553204	ICARIIN	3	4,951
CHEMBL1928262	GISADENAFIL	2	1,176
CHEMBL2110680	ISOMAZOLE	2	267
CHEMBL28079	ZAPRINAST	2	16,158
CHEMBL286020	SULMAZOLE	2
CHEMBL34431	CILOSTAMIDE	2
CHEMBL356323	CIPAMFYLLINE	2
CHEMBL4210847	PF-00489791	2
CHEMBL4297518	MIRODENAFIL	2
CHEMBL591501	PF-03049423	2
CHEMBL63	ROLIPRAM	2
CHEMBL8184	CARTAZOLATE	2
CHEMBL2180408	JNJ-42396302	1
CHEMBL3770459	LENRISPODUN PHOSPHATE	1

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 (16 total), top 16:

Ligand	Action	Affinity	Parameter
compound 53 [PMID: 19631533]	Inhibition	10.3	pIC50
vardenafil	Inhibition	9.7	pIC50
T0156	Inhibition	9.5	pIC50
simenafil	Inhibition	9.21	pIC50
PF-00489791	Inhibition	9.15	pIC50
sildenafil	Inhibition	9.0	pIC50
gisadenafil	Inhibition	8.9	pIC50
tunodafil	Inhibition	8.7	pIC50
tadalafil	Inhibition	8.52	pIC50
udenafil	Inhibition	8.08	pIC50
milrinone	Inhibition	7.31	pIC50
SCH51866	Inhibition	7.2	pIC50
zaprinast	Inhibition	6.8	pIC50
compound 3m [PMID: 32603117]	Inhibition	6.43	pIC50
icariin	Inhibition	5.23	pIC50
ibudilast	Inhibition	3.99	pIC50

Binding affinities (BindingDB)

179 measured of 235 human assays (248 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-[(3-chloro-4-methoxyphenyl)methoxy]-N-(pyridin-2-ylmethyl)pyrimidine-5-carboxamide	IC50	0.028 nM	US-8980904: Heterocyclic substituted pyrimidine compound
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-[(3-chloro-4-methoxyphenyl)methoxy]-N-[(4-fluorophenyl)methyl]pyrimidine-5-carboxamide	IC50	0.075 nM	US-8980904: Heterocyclic substituted pyrimidine compound
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-[(3-chloro-4-methoxyphenyl)methoxy]-N-(pyrimidin-2-ylmethyl)pyrimidine-5-carboxamide	IC50	0.1 nM	US-8980904: Heterocyclic substituted pyrimidine compound
2-(5-azaspiro[2.4]heptan-5-yl)-N-benzyl-4-[(3-chloro-4-methoxyphenyl)methoxy]pyrimidine-5-carboxamide	IC50	0.119 nM	US-8980904: Heterocyclic substituted pyrimidine compound
2-[5-[4-(2-hydroxyethyl)piperidin-1-yl]sulfonyl-2-propoxycyclohexa-1,3-dien-1-yl]-6-[(E)-hydroxyiminomethyl]-5-methyl-7-propyl-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one	IC50	0.16 nM	US-12351585: 2-phenyl-3,4-dihydropyrrolo[2,1-f] [1,2,4]triazinone derivatives as phosphodiesterase inhibitors and uses thereof
2-(3-azabicyclo[3.1.0]hexan-3-yl)-N-benzyl-4-[(3-chloro-4-methoxyphenyl)methoxy]pyrimidine-5-carboxamide	IC50	0.172 nM	US-8980904: Heterocyclic substituted pyrimidine compound
2-(6-azaspiro[2.5]octan-6-yl)-4-[(3-chloro-4-methoxyphenyl)methoxy]-N-(pyridin-2-ylmethyl)pyrimidine-5-carboxamide	IC50	0.186 nM	US-8980904: Heterocyclic substituted pyrimidine compound
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-[(3-chloro-4-methoxyphenyl)methoxy]-N-(2-morpholin-4-ylethyl)pyrimidine-5-carboxamide	IC50	0.213 nM	US-8980904: Heterocyclic substituted pyrimidine compound
3-[1-[(2,3-difluoro-4-methylphenyl)methyl]-5-fluoro-6-methylpyrazolo[3,4-b]pyridin-3-yl]-7,7-dimethyl-5H-pyrrolo[2,3-e][1,2,4]triazin-6-one	IC50	0.25 nM	US-9605008: Benzyl-1H-pyrazolo[3,4-b]pyridines and use thereof
2-(6-azaspiro[2.5]octan-6-yl)-4-[(3-chloro-4-methoxyphenyl)methoxy]-N-(pyrimidin-2-ylmethyl)pyrimidine-5-carboxamide	IC50	0.476 nM	US-8980904: Heterocyclic substituted pyrimidine compound
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-[(3-chloro-4-methoxyphenyl)methoxy]-N-[(5-methylpyrazin-2-yl)methyl]pyrimidine-5-carboxamide	IC50	0.529 nM	US-8980904: Heterocyclic substituted pyrimidine compound
6-[(E)-methoxyiminomethyl]-5-methyl-2-[5-(4-methylpiperazin-1-yl)sulfonyl-2-propoxyphenyl]-7-propyl-6,7-dihydro-3H-pyrrolo[2,1-f][1,2,4]triazin-4-one	IC50	0.53 nM	US-12351585: 2-phenyl-3,4-dihydropyrrolo[2,1-f] [1,2,4]triazinone derivatives as phosphodiesterase inhibitors and uses thereof
3-[1-[(2,3-difluoro-4-methylphenyl)methyl]-6-methylpyrazolo[5,4-b]pyridin-3-yl]-7,7-dimethyl-5H-pyrrolo[2,3-e][1,2,4]triazin-6-one	IC50	0.65 nM	US-9605008: Benzyl-1H-pyrazolo[3,4-b]pyridines and use thereof
2-(6-azaspiro[2.5]octan-6-yl)-4-[(3-chloro-4-methoxyphenyl)methoxy]-N-(4-hydroxycyclohexyl)pyrimidine-5-carboxamide	IC50	0.719 nM	US-8980904: Heterocyclic substituted pyrimidine compound
2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-[(3-chloro-4-methoxyphenyl)methoxy]-N-(4-hydroxycyclohexyl)pyrimidine-5-carboxamide	IC50	0.739 nM	US-8980904: Heterocyclic substituted pyrimidine compound
5-(5-Acetyl-2-butoxy-3-pyridinyl)-3-ethyl-2-[(1-methyl-1H-imidazol-2-yl)methyl]-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one	IC50	0.9 nM
2-(6-azaspiro[2.5]octan-6-yl)-4-[(3-chloro-4-methoxyphenyl)methoxy]-N-(2-morpholin-4-ylethyl)pyrimidine-5-carboxamide	IC50	0.935 nM	US-8980904: Heterocyclic substituted pyrimidine compound
2-(6-azaspiro[2.5]octan-6-yl)-N-benzyl-4-[(3-chloro-4-methoxyphenyl)methoxy]pyrimidine-5-carboxamide	IC50	1.14 nM	US-8980904: Heterocyclic substituted pyrimidine compound
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
2-(5-azaspiro[2.4]heptan-5-yl)-4-[(3-chloro-4-methoxyphenyl)methoxy]-N-(pyrimidin-2-ylmethyl)pyrimidine-5-carboxamide	IC50	1.44 nM	US-8980904: Heterocyclic substituted pyrimidine compound
3-[5-fluoro-1-[(2-fluoro-4-methylphenyl)methyl]-6-methylpyrazolo[3,4-b]pyridin-3-yl]-7,7-dimethyl-5H-pyrrolo[2,3-e][1,2,4]triazin-6-one	IC50	1.5 nM	US-9605008: Benzyl-1H-pyrazolo[3,4-b]pyridines and use thereof
3-(2-(2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-5-methyl-4-oxo-7-propyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-6-yl)-3-hydroxypropanenitrile	IC50	1.5 nM	US-11242347: 2-phenyl-3,4-dihydropyrrolo[2,1-Ff] [1,2,4]triazinone derivatives as phosphodiesterase inhibitors and uses thereof
2-(4-azaspiro[2.4]heptan-4-yl)-N-benzyl-4-[(3-chloro-4-methoxyphenyl)methoxy]pyrimidine-5-carboxamide	IC50	1.98 nM	US-8980904: Heterocyclic substituted pyrimidine compound
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
3-[1-[(2-fluoro-4-methylphenyl)methyl]-6-methylpyrazolo[5,4-b]pyridin-3-yl]-7,7-dimethyl-5H-pyrrolo[2,3-e][1,2,4]triazin-6-one	IC50	2 nM	US-9605008: Benzyl-1H-pyrazolo[3,4-b]pyridines and use thereof
2-(5-azaspiro[2.4]heptan-5-yl)-4-[(3-chloro-4-methoxyphenyl)methoxy]-N-[(4-fluorophenyl)methyl]pyrimidine-5-carboxamide	IC50	2.08 nM	US-8980904: Heterocyclic substituted pyrimidine compound
5-(5-Acetyl-2-butoxy-3-pyridinyl)-3-ethyl-2-[2-(4-morpholinyl)-ethyl]-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one	IC50	2.6 nM
5-(5-Acetyl-2-propoxy-3-pyridinyl)-3-ethyl-2-[(1-methyl-1H-imidazol-2-yl)methyl]-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one	IC50	2.7 nM
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
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
5-(5-Acetyl-2-butoxy-3-pyridinyl)-3-ethyl-2-(1-ethyl-4-piperidinyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one	IC50	3.6 nM
3-[1-[(2,3-difluoro-4-methylphenyl)methyl]-6-methylpyrazolo[5,4-b]pyridin-3-yl]spiro[5H-pyrrolo[2,3-e][1,2,4]triazine-7,1’-cyclopropane]-6-one	IC50	4 nM	US-9605008: Benzyl-1H-pyrazolo[3,4-b]pyridines and use thereof
N-benzyl-4-[(3-chloro-4-methoxyphenyl)methoxy]-2-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrimidine-5-carboxamide	IC50	4.01 nM	US-8980904: Heterocyclic substituted pyrimidine compound
2-(5-azaspiro[2.4]heptan-5-yl)-4-[(3-chloro-4-methoxyphenyl)methoxy]-N-(4-hydroxycyclohexyl)pyrimidine-5-carboxamide	IC50	4.08 nM	US-8980904: Heterocyclic substituted pyrimidine compound
2-[1-[3-[6-[(E)-hydroxyiminomethyl]-5-methyl-4-oxo-7-propyl-3H-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-4-propoxyphenyl]sulfonylpiperidin-4-yl]ethyl nitrate	IC50	4.1 nM	US-12351585: 2-phenyl-3,4-dihydropyrrolo[2,1-f] [1,2,4]triazinone derivatives as phosphodiesterase inhibitors and uses thereof
3-[1-[(4-chloro-2-fluorophenyl)methyl]-6-methylpyrazolo[5,4-b]pyridin-3-yl]-7,7-dimethyl-5H-pyrrolo[2,3-e][1,2,4]triazin-6-one	IC50	4.5 nM	US-9605008: Benzyl-1H-pyrazolo[3,4-b]pyridines and use thereof
N-benzyl-4-[(3-chloro-4-methoxyphenyl)methylamino]-2-[2-(hydroxymethyl)-3-azabicyclo[3.1.0]hexan-3-yl]pyrimidine-5-carboxamide	IC50	4.63 nM	US-9359371: Bicyclic substituted pyrimidine compounds
3-[1-[(2,3-difluorophenyl)methyl]-5-fluoro-6-methylpyrazolo[3,4-b]pyridin-3-yl]-7,7-dimethyl-5H-pyrrolo[2,3-e][1,2,4]triazin-6-one	IC50	5 nM	US-9605008: Benzyl-1H-pyrazolo[3,4-b]pyridines and use thereof
3-[1-[(2,3-difluorophenyl)methyl]-5-fluoro-6-methylpyrazolo[3,4-b]pyridin-3-yl]-7,7-dimethylpyrrolo[2,3-e][1,2,4]triazin-6-olate	IC50	5 nM	US-9605008: Benzyl-1H-pyrazolo[3,4-b]pyridines and use thereof
5-(5-Acetyl-2-propoxy-3-pyridinyl)-3-ethyl-2-(1-isopropyl-3-azetidinyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one	IC50	5.2 nM
3-[1-[(4-chloro-2-fluorophenyl)methyl]-5-fluoro-6-methylpyrazolo[3,4-b]pyridin-3-yl]-7,7-dimethyl-5H-pyrrolo[2,3-e][1,2,4]triazin-6-one	IC50	6 nM	US-9605008: Benzyl-1H-pyrazolo[3,4-b]pyridines and use thereof
5-(5-Acetyl-2-butoxy-3-pyridinyl)-3-ethyl-2-(1-methyl-3-azetidinyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one	IC50	6.4 nM
5-(5-acetyl-2-propoxypyridin-3-yl)-3-ethyl-2-(piperidin-4-yl)-2H,6H,7H-pyrazolo[4,3-d]pyrimidin-7-one	IC50	7 nM
5-(5-acetyl-2-propoxypyridin-3-yl)-3-ethyl-2-(1-ethylazetidin-3-yl)-2H,6H,7H-pyrazolo[4,3-d]pyrimidin-7-one	IC50	7.1 nM
8-chloro-1-cyclohexyl-7-[4-(2-hydroxyethyl)piperazine-1-carbonyl]-8H-imidazo[1,5-a]quinoxalin-4-one	IC50	8 nM	US-8829000: Substituted imidazo[1,5-A]quinoxalines as phosphodiesterase 9 inhibitors
(E)-3-[4-oxo-7-(trifluoromethyl)-9aH-pyrrolo[1,2-a]quinoxalin-1-yl]prop-2-enoic acid	IC50	8 nM	US-8829000: Substituted imidazo[1,5-A]quinoxalines as phosphodiesterase 9 inhibitors
5-[(3-chlorophenyl)methyl]-3-propan-2-yl-3a,6-dihydropyrazolo[4,3-d]pyrimidin-7-one	IC50	8 nM	US-8829000: Substituted imidazo[1,5-A]quinoxalines as phosphodiesterase 9 inhibitors
3-[5-fluoro-1-[(3-fluoro-4-methylphenyl)methyl]-6-methylpyrazolo[3,4-b]pyridin-3-yl]-7,7-dimethyl-5H-pyrrolo[2,3-e][1,2,4]triazin-6-one	IC50	8 nM	US-9605008: Benzyl-1H-pyrazolo[3,4-b]pyridines and use thereof

ChEMBL bioactivities

2415 potent at pChembl≥5 of 2617 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL1916488
11.00	IC50	0.01	nM	CHEMBL1916483
10.96	IC50	0.011	nM	CHEMBL1098465
10.70	IC50	0.02	nM	CHEMBL1916486
10.70	IC50	0.02	nM	CHEMBL1916485
10.70	IC50	0.02	nM	CHEMBL1916475
10.60	IC50	0.025	nM	CHEMBL4759667
10.55	IC50	0.028	nM	CHEMBL3654363
10.54	IC50	0.029	nM	VARDENAFIL
10.52	IC50	0.03	nM	CHEMBL410215
10.40	IC50	0.04	nM	CHEMBL569481
10.40	IC50	0.04	nM	CHEMBL1094365
10.40	IC50	0.04	nM	CHEMBL1916487
10.40	IC50	0.04	nM	CHEMBL1916476
10.36	IC50	0.044	nM	CHEMBL4062273
10.30	IC50	0.05	nM	CHEMBL584270
10.30	IC50	0.05	nM	CHEMBL567470
10.30	IC50	0.05	nM	CHEMBL1094249
10.30	IC50	0.05	nM	CHEMBL38735
10.30	IC50	0.05	nM	CHEMBL1916482
10.30	IC50	0.05	nM	CHEMBL1916303
10.30	IC50	0.05	nM	CHEMBL1916293
10.30	IC50	0.05	nM	CHEMBL1916292
10.25	IC50	0.056	nM	CHEMBL4062273
10.23	IC50	0.059	nM	CHEMBL4072903
10.22	IC50	0.06	nM	CHEMBL565305
10.22	IC50	0.06	nM	CHEMBL1916489
10.15	IC50	0.07	nM	CHEMBL551052
10.15	IC50	0.07	nM	CHEMBL5942848
10.15	IC50	0.07	nM	CHEMBL568839
10.15	IC50	0.07	nM	CHEMBL585918
10.15	IC50	0.07	nM	CHEMBL1094544
10.15	IC50	0.07	nM	CHEMBL1098466
10.15	IC50	0.07	nM	CHEMBL1097506
10.15	IC50	0.07	nM	CHEMBL1095121
10.13	IC50	0.074	nM	CHEMBL5723336
10.12	IC50	0.075	nM	CHEMBL3654365
10.10	IC50	0.08	nM	CHEMBL566598
10.10	IC50	0.08	nM	CHEMBL1097823
10.10	IC50	0.08	nM	CHEMBL1098141
10.10	IC50	0.08	nM	CHEMBL1916291
10.06	IC50	0.087	nM	CHEMBL1094191
10.05	IC50	0.09	nM	CHEMBL566367
10.05	IC50	0.09	nM	CHEMBL1095406
10.05	IC50	0.09	nM	CHEMBL1916299
10.00	IC50	0.1	nM	CHEMBL3654362
10.00	IC50	0.1	nM	CHEMBL5081214
10.00	IC50	0.1	nM	CHEMBL567471
10.00	IC50	0.1	nM	CHEMBL344018
10.00	IC50	0.1	nM	CHEMBL1916290

PubChem BioAssay actives

2079 with measured affinity, of 3507 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[13-[(3-chloro-4-methoxyphenyl)methylamino]-5-ethyl-4,5,7,11,12-pentazatricyclo[7.4.0.02,6]trideca-1,3,6,8,10,12-hexaen-10-yl]piperidine-4-carboxylic acid	157951: Inhibition of Phosphodiesterase 5 from human platelets	ic50	<0.0001	uM
5-[4-(aminomethyl)piperidin-1-yl]-1-(2-ethoxyethyl)-3-ethyl-N-(4-methyl-2-pyridinyl)pyrazolo[4,5-d]pyrimidin-7-amine	481330: Inhibition of PDE5 in human platelet by assessed as hydrolysis of [3H]cGMP scintillation proximity assay	ic50	<0.0001	uM
7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)-3-(pyridin-2-ylmethylamino)pyrido[3,4-b]pyrazin-2-one	446781: Inhibition of PDE5	ic50	<0.0001	uM
Vardenafil	1704612: Inhibition of human platelets derived PDE5 using [3H]-cGMP as substrate incubated for 60 min by scintillation proximity assay	ic50	<0.0001	uM
1-[1-(2-ethoxyethyl)-3-ethyl-7-[(4-methyl-2-pyridinyl)amino]pyrazolo[4,5-d]pyrimidin-5-yl]piperidine-4-carboxylic acid	481330: Inhibition of PDE5 in human platelet by assessed as hydrolysis of [3H]cGMP scintillation proximity assay	ic50	<0.0001	uM
2-[2-ethoxy-5-[(1-imino-1-oxo-1,4-thiazinan-4-yl)sulfonyl]phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one	1704612: Inhibition of human platelets derived PDE5 using [3H]-cGMP as substrate incubated for 60 min by scintillation proximity assay	ic50	<0.0001	uM
1-(2-ethoxyethyl)-3-ethyl-7-N-(4-methyl-2-pyridinyl)-5-N-(piperidin-4-ylmethyl)pyrazolo[4,5-d]pyrimidine-5,7-diamine	481330: Inhibition of PDE5 in human platelet by assessed as hydrolysis of [3H]cGMP scintillation proximity assay	ic50	<0.0001	uM
8-[(4-hydroxycyclohexyl)amino]-3-(6-methoxy-3-pyridinyl)-5-(2-propoxyethyl)pyrimido[5,4-c]pyridazin-6-one	630828: Inhibition of PDE5	ic50	<0.0001	uM
2-[1-[3-(6-methoxy-3-pyridinyl)-6-oxo-5-(2-propoxyethyl)pyrimido[5,4-c]pyridazin-8-yl]piperidin-4-yl]acetic acid	630828: Inhibition of PDE5	ic50	<0.0001	uM
1-[3-(6-methoxy-3-pyridinyl)-6-oxo-5-(2-propoxyethyl)pyrimido[5,4-c]pyridazin-8-yl]piperidine-4-carboxylic acid	630828: Inhibition of PDE5	ic50	<0.0001	uM
3-[[3-(6-methoxy-3-pyridinyl)-6-oxo-5-(2-propoxyethyl)pyrimido[5,4-c]pyridazin-8-yl]amino]cyclohexane-1-carboxylic acid	630828: Inhibition of PDE5	ic50	<0.0001	uM
8-[(4-hydroxycyclohexyl)amino]-3-(6-methoxy-3-pyridinyl)-5-[2-(2,2,2-trifluoroethoxy)ethyl]pyrimido[5,4-c]pyridazin-6-one	630828: Inhibition of PDE5	ic50	<0.0001	uM
4-[[3-(6-methoxy-3-pyridinyl)-6-oxo-5-(2-propoxyethyl)pyrimido[5,4-c]pyridazin-8-yl]amino]cyclohexane-1-carboxylic acid	630828: Inhibition of PDE5	ic50	<0.0001	uM
cis-(1S,2R)-2-[[3-(6-methoxy-3-pyridinyl)-6-oxo-5-(2-propoxyethyl)pyrimido[5,4-c]pyridazin-8-yl]amino]cyclohexane-1-carboxylic acid	630828: Inhibition of PDE5	ic50	<0.0001	uM
4-[(3-chloro-4-methoxyphenyl)methylamino]-8-ethyl-3-(hydroxymethyl)quinoline-6-carbonitrile	157947: Inhibition of phosphodiesterase 5 from human platelets	ic50	0.0001	uM
3-ethyl-5-[(3R)-3-methylpiperazin-1-yl]-N-pyrimidin-4-yl-1-[2-(2,2,2-trifluoroethoxy)ethyl]pyrazolo[4,5-d]pyrimidin-7-amine	481312: Inhibition of PDE5	ic50	0.0001	uM
3-methyl-5-[(3R)-3-methylpiperazin-1-yl]-N-pyrimidin-4-yl-1-[2-(2,2,2-trifluoroethoxy)ethyl]pyrazolo[4,5-d]pyrimidin-7-amine	481312: Inhibition of PDE5	ic50	0.0001	uM
1-[1-(2-ethoxyethyl)-3-ethyl-7-[(4-methyl-2-pyridinyl)amino]pyrazolo[4,5-d]pyrimidin-5-yl]piperidine-3-carboxamide	481330: Inhibition of PDE5 in human platelet by assessed as hydrolysis of [3H]cGMP scintillation proximity assay	ic50	0.0001	uM
3-ethyl-N-(4-fluorophenyl)-5-piperazin-1-yl-1-[2-(2,2,2-trifluoroethoxy)ethyl]pyrazolo[4,5-d]pyrimidin-7-amine	481312: Inhibition of PDE5	ic50	0.0001	uM
[1-[1-(2-ethoxyethyl)-3-ethyl-7-[(4-methyl-2-pyridinyl)amino]pyrazolo[4,5-d]pyrimidin-5-yl]piperidin-4-yl]methanol	481330: Inhibition of PDE5 in human platelet by assessed as hydrolysis of [3H]cGMP scintillation proximity assay	ic50	0.0001	uM
3-(1,3-benzodioxol-5-yl)-2-(5-pyridin-3-ylfuran-2-carbonyl)-3,4-dihydro-1H-pyrrolo[3,4-b]quinolin-9-one	158117: Inhibitory activity against Phosphodiesterase 5 (PDE5) was evaluated	ki	0.0001	uM
9-[(3-chloro-4-methoxyphenyl)methylamino]-2-ethyl-1-oxo-3H-pyrrolo[3,4-b]quinoline-7-carbonitrile	1465725: Inhibition of human recombinant PDE5A1 using FAM-labelled cGMP as substrate after 60 mins by fluorescence polarization assay	ic50	0.0001	uM
3-(2-ethoxyethylamino)-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446781: Inhibition of PDE5	ic50	0.0001	uM
3-[(4-hydroxycyclohexyl)amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446781: Inhibition of PDE5	ic50	0.0001	uM
3-[[(2R)-2-hydroxypropyl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446781: Inhibition of PDE5	ic50	0.0001	uM
3-[[(2S)-2-hydroxypropyl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446781: Inhibition of PDE5	ic50	0.0001	uM
3-[[(2R)-1-hydroxypropan-2-yl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446781: Inhibition of PDE5	ic50	0.0001	uM
2-[[7-(6-methoxy-3-pyridinyl)-2-oxo-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-3-yl]amino]-N-methylacetamide	446781: Inhibition of PDE5	ic50	0.0001	uM
7-(6-methoxy-3-pyridinyl)-3-(2-morpholin-4-ylethylamino)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	428473: Inhibition of PDE5	ic50	0.0001	uM
7-(6-methoxy-3-pyridinyl)-3-(oxolan-2-ylmethylamino)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446781: Inhibition of PDE5	ic50	0.0001	uM
7-(6-methoxy-3-pyridinyl)-3-(oxan-4-ylmethylamino)-1-(2-propoxyethyl)pyrido[2,3-b]pyrazin-2-one	446781: Inhibition of PDE5	ic50	0.0001	uM
7-(6-methoxy-3-pyridinyl)-3-[(2-morpholin-4-yl-2-oxoethyl)amino]-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446781: Inhibition of PDE5	ic50	0.0001	uM
3-[[2-(4-ethylpiperazin-1-yl)-2-oxoethyl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446781: Inhibition of PDE5	ic50	0.0001	uM
7-(6-methoxy-3-pyridinyl)-3-[(2-oxo-2-pyrrolidin-1-ylethyl)amino]-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446781: Inhibition of PDE5	ic50	0.0001	uM
7-(6-methoxy-3-pyridinyl)-3-[[2-(4-methylpiperazin-1-yl)-2-oxoethyl]amino]-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446781: Inhibition of PDE5	ic50	0.0001	uM
3-[[2-(4-hydroxypiperidin-1-yl)-2-oxoethyl]amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2-one	446781: Inhibition of PDE5	ic50	0.0001	uM
1-ethyl-3-methyl-6-(5-nitro-2-propoxyphenyl)-5H-pyrazolo[5,4-d]pyrimidin-4-one	157942: Inhibition of Phosphodiesterase 5 from human	ic50	0.0001	uM
(2R,8R)-2-(1,3-benzodioxol-5-yl)-6-[2-(1-benzylpiperidin-4-yl)ethyl]-3,6,17-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1(10),11,13,15-tetraene-4,7-dione	2124210: Inhibition of PDE5A (unknown origin)	ic50	0.0001	uM
7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)-3-(pyrazin-2-ylmethylamino)pyrido[3,4-b]pyrazin-2-one	446781: Inhibition of PDE5	ic50	0.0001	uM
3-ethyl-5-piperazin-1-yl-N-pyrimidin-4-yl-1-[2-(2,2,2-trifluoroethoxy)ethyl]pyrazolo[4,5-d]pyrimidin-7-amine	481312: Inhibition of PDE5	ic50	0.0001	uM
1-(2-ethoxyethyl)-3-ethyl-N-phenyl-5-piperazin-1-ylpyrazolo[4,5-d]pyrimidin-7-amine	481330: Inhibition of PDE5 in human platelet by assessed as hydrolysis of [3H]cGMP scintillation proximity assay	ic50	0.0001	uM
1-(2-ethoxyethyl)-3-ethyl-5-N-methyl-5-N-(1-methylpiperidin-4-yl)-7-N-(4-methyl-2-pyridinyl)pyrazolo[4,5-d]pyrimidine-5,7-diamine	481330: Inhibition of PDE5 in human platelet by assessed as hydrolysis of [3H]cGMP scintillation proximity assay	ic50	0.0001	uM
5-[4-(aminomethyl)piperidin-1-yl]-1-(2-ethoxyethyl)-3-methyl-N-(4-methyl-2-pyridinyl)pyrazolo[4,5-d]pyrimidin-7-amine	481330: Inhibition of PDE5 in human platelet by assessed as hydrolysis of [3H]cGMP scintillation proximity assay	ic50	0.0001	uM
1-[1-(2-ethoxyethyl)-3-ethyl-7-[(4-methyl-2-pyridinyl)amino]pyrazolo[4,5-d]pyrimidin-5-yl]piperidine-4-carboxamide	481330: Inhibition of PDE5 in human platelet by assessed as hydrolysis of [3H]cGMP scintillation proximity assay	ic50	0.0001	uM
1-[1-(2-ethoxyethyl)-3-methyl-7-[(4-methyl-2-pyridinyl)amino]pyrazolo[4,5-d]pyrimidin-5-yl]piperidine-4-carboxylic acid	481330: Inhibition of PDE5 in human platelet by assessed as hydrolysis of [3H]cGMP scintillation proximity assay	ic50	0.0001	uM
7-(6-methoxy-3-pyridinyl)-4-(2-propan-2-yloxyethylamino)-1-(2-propoxyethyl)pyrido[4,3-d]pyrimidin-2-one	630828: Inhibition of PDE5	ic50	0.0001	uM
3-(6-methoxy-3-pyridinyl)-8-(2-morpholin-4-ylethylamino)-5-(2-propoxyethyl)pyrimido[5,4-c]pyridazin-6-one	630828: Inhibition of PDE5	ic50	0.0001	uM
3-[[3-(6-methoxy-3-pyridinyl)-6-oxo-5-(2-propoxyethyl)pyrimido[5,4-c]pyridazin-8-yl]amino]propanoic acid	630828: Inhibition of PDE5	ic50	0.0001	uM
2-[[3-(6-methoxy-3-pyridinyl)-6-oxo-5-(2-propoxyethyl)pyrimido[5,4-c]pyridazin-8-yl]amino]-2-methylpropanoic acid	630828: Inhibition of PDE5	ic50	0.0001	uM
4-[(4-hydroxycyclohexyl)amino]-7-(6-methoxy-3-pyridinyl)-1-(2-propoxyethyl)pyrido[3,2-d]pyrimidin-2-one	630828: Inhibition of PDE5	ic50	0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Sildenafil Citrate	decreases activity	6
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance, increases expression	4
Tadalafil	decreases activity	4
Vardenafil Dihydrochloride	decreases activity	4
Valproic Acid	decreases methylation, affects expression, decreases expression	4
Copper	affects binding, increases expression	3
Estradiol	affects expression, decreases expression, increases reaction	3
sulindac sulfone	affects binding, decreases activity	2
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	increases expression	2
Particulate Matter	decreases expression, increases abundance	2
afuresertib	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
pentanal	increases expression	1
avobenzone	increases expression	1
MY 5445	decreases activity	1
icariin	decreases activity	1
polydatin	decreases activity	1
malvidin	decreases activity	1
udenafil	decreases activity	1

ChEMBL screening assays

509 unique, capped per target: 492 binding, 9 admet, 7 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1011852	Binding	Inhibition of PDE5	Identification of potent pyrimidine inhibitors of phosphodiesterase 7 (PDE7) and their ability to inhibit T cell proliferation. — Bioorg Med Chem Lett
CHEMBL4021628	ADMET	Inhibition of PDE5A1 (unknown origin) at 5 uM using fluorescein-labeled cGMP as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins by IMAP fluorescence polarization assay relative to control	Design and optimization of purine derivatives as in vivo active PDE10A inhibitors. — Bioorg Med Chem
CHEMBL5723295	Functional	Affinity Biochemical interaction: (inhibition of enzyme activity in cleaving radiolabelled substrate [3H]cGMP) EUB0002742aCl PDE5A	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C7DE	Abcam A-549 PDE5A KO	Cancer cell line	Male
CVCL_C7E4	Abcam HCT 116 PDE5A KO	Cancer cell line	Male
CVCL_D1TW	Abcam U-87MG PDE5A KO	Cancer cell line	Male
CVCL_TC67	HAP1 PDE5A (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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