PDE4C

Summary

PDE4C (phosphodiesterase 4C, HGNC:8782) is a protein-coding gene on chromosome 19p13.11, encoding 3’,5’-cyclic-AMP phosphodiesterase 4C (Q08493). 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 PDE4 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 5143 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 91 total
• Druggable target: yes — 48 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001098818

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8782
Approved symbol	PDE4C
Name	phosphodiesterase 4C
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000105650
Ensembl biotype	protein_coding
OMIM	600128
Entrez	5143

Gene structure

Transcript identifiers

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

ENST00000262805, ENST00000447275, ENST00000539010, ENST00000593594, ENST00000594465, ENST00000594617, ENST00000595343, ENST00000597297, ENST00000597360, ENST00000597573, ENST00000598111, ENST00000599188, ENST00000599754, ENST00000610023

RefSeq mRNA: 6 — MANE Select: NM_001098818 NM_000923, NM_001098818, NM_001098819, NM_001330172, NM_001369701, NM_001395274

CCDS: CCDS12373, CCDS42523, CCDS46016, CCDS92567

Canonical transcript exons

ENST00000262805 — 15 exons

Exon	Start	End
ENSE00003818344	18220226	18220319
ENSE00003818525	18218334	18218498
ENSE00003818552	18219234	18219397
ENSE00003819716	18220874	18220923
ENSE00003820982	18218149	18218248
ENSE00003824239	18221261	18221297
ENSE00003824892	18222132	18222323
ENSE00003824953	18220403	18220515
ENSE00003825745	18221105	18221178
ENSE00003828346	18218940	18219038
ENSE00003830081	18216741	18216895
ENSE00003830309	18211759	18211941
ENSE00003830787	18213368	18213490
ENSE00003978158	18226270	18226438
ENSE00003978159	18207965	18211276

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 84.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3765 / max 86.3165, expressed in 114 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179944	0.3336	103
179945	0.0428	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	84.78	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.79	gold quality
tibial artery	UBERON:0007610	76.71	gold quality
popliteal artery	UBERON:0002250	76.66	gold quality
spleen	UBERON:0002106	75.86	gold quality
skeletal muscle tissue	UBERON:0001134	75.67	gold quality
muscle of leg	UBERON:0001383	75.46	gold quality
gastrocnemius	UBERON:0001388	74.82	gold quality
heart left ventricle	UBERON:0002084	74.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.73	gold quality
muscle layer of sigmoid colon	UBERON:0035805	73.18	gold quality
stromal cell of endometrium	CL:0002255	73.08	gold quality
right coronary artery	UBERON:0001625	72.67	gold quality
muscle tissue	UBERON:0002385	72.17	gold quality
superior frontal gyrus	UBERON:0002661	71.75	gold quality
placenta	UBERON:0001987	71.58	gold quality
mucosa of stomach	UBERON:0001199	71.33	gold quality
metanephros cortex	UBERON:0010533	71.21	gold quality
heart	UBERON:0000948	71.19	gold quality
transverse colon	UBERON:0001157	70.94	gold quality
colon	UBERON:0001155	70.55	gold quality
body of uterus	UBERON:0009853	70.47	gold quality
fundus of stomach	UBERON:0001160	70.44	gold quality
left coronary artery	UBERON:0001626	69.93	gold quality
smooth muscle tissue	UBERON:0001135	69.91	gold quality
prefrontal cortex	UBERON:0000451	69.66	gold quality
frontal cortex	UBERON:0001870	69.44	gold quality
upper lobe of left lung	UBERON:0008952	69.37	gold quality
body of stomach	UBERON:0001161	69.28	gold quality
right ovary	UBERON:0002118	69.27	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-85	yes	60.32
E-ANND-3	no	1.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting PDE4C, 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-1252-5P	100.00	69.80	2774
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-4722-3P	99.35	65.22	1099

Literature-anchored findings (GeneRIF, showing 3)

• PDE4A and PDE4C work in redundant fashion to mediate the loss of inhibitory PGE2 signaling in lung fibroblasts. (PMID:23043089)
• Data show that PDE4C is downregulated through promoter hypermethylation in glioma. (PMID:24842301)
• Analysis of the effects of M2 macrophage-derived PDE4C on the prognosis, metastasis and immunotherapy benefit of osteosarcoma. (PMID:38774995)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	pde11al	ENSDARG00000006151
danio_rerio	si:dkey-219c10.4	ENSDARG00000075929
mus_musculus	Pde4c	ENSMUSG00000031842
rattus_norvegicus	Pde4c	ENSRNOG00000019518
drosophila_melanogaster	Pde11	FBGN0085370
drosophila_melanogaster	Pde9	FBGN0259171
drosophila_melanogaster	Pde8	FBGN0266377
caenorhabditis_elegans		WBGENE00008443
caenorhabditis_elegans	pde-6	WBGENE00022389

Paralogs (20): PDE4A (ENSG00000065989), PDE8A (ENSG00000073417), PDE6C (ENSG00000095464), 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), PDE7A (ENSG00000205268)

Protein

Protein identifiers

3’,5’-cyclic-AMP phosphodiesterase 4C — Q08493 (reviewed: Q08493)

Alternative names: DPDE1, PDE21, cAMP-specific phosphodiesterase 4C

All UniProt accessions (8): Q08493, A0A2R9YJK9, B7Z6T1, M0R1P5, Q32MM7, U3KPR3, U3KPR4, V9GYP2

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

Subunit / interactions. Part of a complex containing AKAP5, ADCY5, ADCY6 and PKD2.

Subcellular location. Cell projection. Cilium.

Tissue specificity. Expressed in various tissues but not in cells of the immune system.

Activity regulation. Inhibited by rolipram.

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

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. PDE4 subfamily.

Isoforms (7)

UniProt ID	Names	Canonical?
Q08493-1	PDE4C1	yes
Q08493-2	PDE4C2
Q08493-3	PDE4C3
Q08493-4	PDE4C4
Q08493-5	PDE4C5
Q08493-6	PDE4C6
Q08493-7	PDE4C7

RefSeq proteins (6): NP_000914, NP_001092288, NP_001092289, NP_001317101, NP_001356630, NP_001382203 (=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
IPR040844	PDE4_UCR	Domain

Pfam: PF00233, PF18100

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 (66 total): helix 21, binding site 16, region of interest 5, sequence conflict 5, sequence variant 4, turn 4, compositionally biased region 3, modified residue 2, splice variant 2, chain 1, domain 1, active site 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2QYM	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08493-F1	71.70	0.44

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): 388 (proton donor)

Ligand- & substrate-binding residues (16): 388; 388; 392; 392; 428; 429; 429; 429; 429; 429; 546; 546 …

Post-translational modifications (2): 73, 641

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-180024	DARPP-32 events
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 141 (showing top): GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CYCLIC_NUCLEOTIDE_METABOLIC_PROCESS, GOBP_CYCLIC_NUCLEOTIDE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, NFKB_Q6, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, LIAO_METASTASIS, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, KEGG_PURINE_METABOLISM, MODULE_88, GOBP_NUCLEOSIDE_PHOSPHATE_CATABOLIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_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), 3’,5’-cyclic-nucleotide phosphodiesterase activity (GO:0004114), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), cytosol (GO:0005829), cilium (GO:0005929), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Opioid Signalling	1
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
cyclic-nucleotide phosphodiesterase activity	1
binding	1
phosphoric ester hydrolase activity	1
catalytic activity	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

656 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE4C	ALDH7A1	P49419	909
PDE4C	PKD2	Q13563	899
PDE4C	ADCY5	O95622	872
PDE4C	SLC25A19	Q9HC21	646
PDE4C	JUND	P17535	606
PDE4C	EDARADD	Q8WWZ3	599
PDE4C	RAB3A	P20336	590
PDE4C	ELOVL2	Q9NXB9	580
PDE4C	AKAP5	P24588	550
PDE4C	ELOVL5	Q9NYP7	507
PDE4C	POU1F1	P28069	491
PDE4C	CCDC102B	Q68D86	479
PDE4C	GNAI2	P04899	463
PDE4C	TSKU	Q8WUA8	459
PDE4C	ADCY6	O43306	447

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ECE1	PDE4C	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (11): SRI (Two-hybrid), PDE4C (Two-hybrid), PDE4C (Two-hybrid), PDE4C (Two-hybrid), PDE4C (Two-hybrid), MEOX2 (Two-hybrid), OSGIN1 (Two-hybrid), DDIT4L (Two-hybrid), ZNF280A (Two-hybrid), KLRK1 (Two-hybrid), PDE4C (Negative Genetic)

ESM2 similar proteins: A0A1W2PPD8, A2A3K4, A4Q9E5, A4Q9F0, A4Q9F1, A6PVC2, A7E379, B2GUB3, D3YWQ0, F1MAB7, O00295, O15021, O75912, O89084, O94953, O94966, P03177, P15304, P46686, P54748, Q08493, Q0P4M4, Q14999, Q1ECV4, Q1HVD1, Q28969, Q3KSQ2, Q3ULB5, Q4G017, Q5R8Z4, Q5R978, Q5RCJ3, Q5TKR9, Q6EEF3, Q6EMB2, Q6J1Y9, Q6NZK8, Q6X4W1, Q6ZT98, Q7TNN8

Diamond homologs: A0A077YBL0, B7YZV4, O18696, O60658, O88502, O89084, O95263, P06776, P12252, P14100, P14270, P14644, P14646, P27815, P30645, P54748, P54750, Q01061, Q01063, Q01064, Q01065, Q01066, Q07343, Q08493, Q08499, Q14123, Q3UEI1, Q61481, Q63421, Q64338, Q64395, Q6NNF2, Q86H13, Q8I5V4, Q8IRU4, Q9I7S6, Q9N2V9, Q9W4S9, Q9W4T4, B3LVW5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MAPK1	down-regulates	PDE4C	phosphorylation
PKA	“up-regulates activity”	PDE4C	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3931 predictions. Top by Δscore:

Variant	Effect	Δscore
19:18211272:CCCAC:C	acceptor_gain	1.0000
19:18211273:CCACC:C	acceptor_gain	1.0000
19:18211822:A:AC	donor_gain	1.0000
19:18211823:C:CC	donor_gain	1.0000
19:18211823:CG:C	donor_gain	1.0000
19:18213364:ACAC:A	donor_loss	1.0000
19:18213365:CACCT:C	donor_loss	1.0000
19:18213366:A:AC	donor_gain	1.0000
19:18213366:ACCT:A	donor_loss	1.0000
19:18213367:C:CA	donor_loss	1.0000
19:18213367:C:CC	donor_gain	1.0000
19:18213367:CCTGG:C	donor_gain	1.0000
19:18213486:AGCAC:A	acceptor_gain	1.0000
19:18213487:GCAC:G	acceptor_gain	1.0000
19:18213488:CAC:C	acceptor_gain	1.0000
19:18213488:CACC:C	acceptor_gain	1.0000
19:18213489:ACCT:A	acceptor_loss	1.0000
19:18213491:CTGG:C	acceptor_loss	1.0000
19:18216736:CTCA:C	donor_loss	1.0000
19:18216738:CACCA:C	donor_loss	1.0000
19:18216739:A:AC	donor_gain	1.0000
19:18216740:C:CC	donor_gain	1.0000
19:18216740:C:T	donor_loss	1.0000
19:18216755:T:TA	donor_gain	1.0000
19:18216869:CGT:C	acceptor_gain	1.0000
19:18216871:T:TC	acceptor_gain	1.0000
19:18218144:CTT:C	donor_loss	1.0000
19:18218144:CTTA:C	donor_gain	1.0000
19:18218145:TTA:T	donor_loss	1.0000
19:18218146:TA:T	donor_loss	1.0000

AlphaMissense

4443 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:18211234:A:G	W612R	0.998
19:18211234:A:T	W612R	0.998
19:18211243:A:G	W609R	0.998
19:18211243:A:T	W609R	0.998
19:18211268:G:C	F600L	0.998
19:18211268:G:T	F600L	0.998
19:18211270:A:G	F600L	0.998
19:18211801:A:C	S583R	0.998
19:18211801:A:T	S583R	0.998
19:18211803:T:G	S583R	0.998
19:18211176:C:G	R631P	0.997
19:18211224:A:G	L615P	0.997
19:18213444:A:G	L511P	0.997
19:18218193:T:A	D429V	0.997
19:18220473:A:G	L213P	0.997
19:18221156:A:T	V165D	0.997
19:18211269:A:G	F600S	0.996
19:18211872:A:G	W560R	0.996
19:18211872:A:T	W560R	0.996
19:18211906:G:C	S548R	0.996
19:18211906:G:T	S548R	0.996
19:18211908:T:G	S548R	0.996
19:18220318:A:G	F237S	0.996
19:18222206:G:C	F120L	0.996
19:18222206:G:T	F120L	0.996
19:18222208:A:G	F120L	0.996
19:18211231:C:G	A613P	0.995
19:18218162:A:C	F439L	0.995
19:18218162:A:T	F439L	0.995
19:18218164:A:G	F439L	0.995

dbSNP variants (sampled 300 via entrez): RS1000039674 (19:18227063 C>T), RS1000088975 (19:18220633 C>T), RS1000101105 (19:18234786 C>T), RS1000127365 (19:18240133 A>C), RS1000231320 (19:18249768 T>C), RS1000483056 (19:18238393 G>A), RS1000510179 (19:18248096 C>T), RS1000575616 (19:18208228 G>A), RS1000598156 (19:18225460 C>G), RS1000678914 (19:18242417 A>G), RS1000722200 (19:18231280 T>C,G), RS1000817102 (19:18237102 G>A,C), RS1000861634 (19:18218729 AGGGCCAGGGGCC>A), RS1000915984 (19:18220347 G>A,T), RS1000916799 (19:18213052 G>A)

Disease associations

OMIM: gene MIM:600128 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST008971_112	Urate levels	1.000000e-08
GCST010204_124	Low density lipoprotein cholesterol levels	6.000000e-12
GCST010243_235	Apolipoprotein B levels	4.000000e-10
GCST010245_129	LDL cholesterol levels	6.000000e-12
GCST012228_599	Waist-hip index	9.000000e-09
GCST012230_153	Waist-to-hip ratio adjusted for BMI	3.000000e-09
GCST90016672_2	Abdominal subcutaneous adipose tissue volume	2.000000e-08
GCST90020024_533	A body shape index	8.000000e-12
GCST90020024_535	A body shape index	1.000000e-11
GCST90020025_1424	Waist-to-hip ratio adjusted for BMI	7.000000e-10
GCST90020025_1425	Waist-to-hip ratio adjusted for BMI	7.000000e-13
GCST90020025_1426	Waist-to-hip ratio adjusted for BMI	2.000000e-11
GCST90020025_1427	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020025_1429	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST90020027_136	Waist-hip index	2.000000e-10
GCST90020027_137	Waist-hip index	1.000000e-12
GCST90020027_138	Waist-hip index	6.000000e-12
GCST90020027_139	Waist-hip index	8.000000e-09
GCST90020027_271	Waist-hip index	2.000000e-08
GCST90020029_19	Waist circumference adjusted for body mass index	1.000000e-09
GCST90020029_21	Waist circumference adjusted for body mass index	2.000000e-12
GCST90020029_22	Waist circumference adjusted for body mass index	1.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2093863 (PROTEIN FAMILY), CHEMBL2095153 (SELECTIVITY GROUP), CHEMBL2111340 (SELECTIVITY GROUP), CHEMBL2363066 (PROTEIN FAMILY), CHEMBL291 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

48 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 391,094 (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
CHEMBL12856	INAMRINONE	4	9,690
CHEMBL1355736	THEOPHYLLINE	4	752
CHEMBL1520	VARDENAFIL	4	21,078
CHEMBL189	MILRINONE	4	20,605
CHEMBL191	LOSARTAN	4	88,932
CHEMBL192	SILDENAFIL	4	41,819
CHEMBL193240	ROFLUMILAST	4	19,604
CHEMBL249856	ENOXIMONE	4	5,206
CHEMBL4594287	ENSIFENTRINE	4	499
CHEMBL484785	CRISABOROLE	4	1,482
CHEMBL514800	APREMILAST	4	4,576
CHEMBL628	PENTOXIFYLLINE	4	26,061
CHEMBL779	TADALAFIL	4	23,417
CHEMBL932	DIPYRIDAMOLE	4	51,743
CHEMBL19449	IBUDILAST	4	7,461
CHEMBL332750	TETOMILAST	3	854
CHEMBL5095240	MUFEMILAST	3	103
CHEMBL511115	CILOMILAST	3	1,703
CHEMBL19224	PAPAVERINE	3	22,172
CHEMBL11417	STREPTONIGRIN	2	43,337
CHEMBL12831	IMAZODAN	2
CHEMBL17125	PELRINONE	2
CHEMBL2106994	PUMAFENTRINE	2
CHEMBL2107085	TOCLADESINE	2
CHEMBL2165191	AZD-6482	2
CHEMBL277465	DENBUFYLLINE	2
CHEMBL279898	ENPROFYLLINE	2
CHEMBL28079	ZAPRINAST	2
CHEMBL285913	TREQUINSIN	2
CHEMBL3113974	TRANIMILAST	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs271828	PDE4C		0.00	0

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 (8 total), top 8:

Ligand	Action	Affinity	Parameter
RS-25344	Inhibition	8.1	pIC50
MK-0359	Inhibition	8.04	pIC50
CDP840	Inhibition	7.72	pKi
apremilast	Inhibition	6.93	pIC50
ibudilast	Inhibition	6.62	pIC50
rolipram	Inhibition	6.5	pIC50
6-Hydroxy-5,7-dimethoxyflavone	Inhibition	5.76	pIC50
Ro20-1724	Inhibition	5.4	pIC50

Binding affinities (BindingDB)

115 measured of 149 human assays (149 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL315565	IC50	0.398 nM
3-[(2S)-2-[3-cyclopropoxy-4-(difluoromethoxy)phenyl]-2-[5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-1,3-thiazol-2-yl]ethyl]-1-oxidopyridin-1-ium	IC50	0.4 nM
CHEMBL313982	IC50	0.501 nM
3-(4-Chloro-3-fluorophenyl)-N-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazine-2-carboxamide (7)	IC50	2.35 nM	US-10077269: Imidazopyridazine compounds
N-cyclopropyl-3-[2-(difluoro-methoxy)pyridin-4-yl]imidazo[1,2-b]pyridazine-2-carboxamide	IC50	10.5 nM	US-10077269: Imidazopyridazine compounds
3-(4-chloro-3-fluorophenyl)-N-[(1R,2S)-2-fluorocyclopro-pyl]imidazo[1,2-b]pyridazine-2-carboxamide	IC50	11.7 nM	US-10077269: Imidazopyridazine compounds
3-(4-chloro-3-fluorophenyl)-N-propylimidazo[1,2-b]pyridazine-2-carboxamide	IC50	13.8 nM	US-10077269: Imidazopyridazine compounds
N-cyclopropyl-3-(3-fluoro-4-methylphenyl)imidazo[1,2-b]pyridazine-2-carboxamide	IC50	16.8 nM	US-10077269: Imidazopyridazine compounds
azetidin-1-yl-[3-(4-chloro-3-fluorophenyl)imidazo[1,2-b]pyridazin-2-yl]methanone	IC50	17.3 nM	US-10077269: Imidazopyridazine compounds
azetidin-1-yl-[3-(3-chloro-4-methylphenyl)imidazo[1,2-b]pyridazin-2-yl]methanone	IC50	19 nM	US-10077269: Imidazopyridazine compounds
3-(4-chloro-5-fluoro-2-methylphenyl)-N-propan-2-ylimidazo[1,2-b]pyridazine-2-carboxamide	IC50	20 nM	US-10077269: Imidazopyridazine compounds
bis(ditert-butyl-[4-(dimethylamino)phenyl]phosphanium);dichloropalladium	IC50	20 nM	US-9598421: Imidazopyridazine compounds
3-(3-chlorophenyl)-N-cyclopropylimidazo[1,2-b]pyridazine-2-carboxamide	IC50	21 nM	US-10077269: Imidazopyridazine compounds
azetidin-1-yl-[3-[2-(difluoromethoxy)-4-pyridinyl]imidazo[1,2-b]pyridazin-2-yl]methanone	IC50	22.2 nM	US-10077269: Imidazopyridazine compounds
azetidin-1-yl-[3-(4-chloro-3,5-difluorophenyl)imidazo[1,2-b]pyridazin-2-yl]methanone	IC50	23.9 nM	US-10077269: Imidazopyridazine compounds
3-(4-chlorophenyl)-N-(2-methylcyclopropyl)imidazo[1,2-b]pyridazine-2-carboxamide	IC50	24.5 nM	US-10077269: Imidazopyridazine compounds
3-(4-chloro-2-fluorophenyl)-N-[(1R,2S)-2-fluorocyclopro-pyl]imidazo[1,2-b]pyridazine-2-carboxamide	IC50	25.1 nM	US-10077269: Imidazopyridazine compounds
3-(4-cyano-3-fluorophenyl)-N-cyclopropylimidazo[1,2-b]pyridazine-2-carboxamide	IC50	25.5 nM	US-10077269: Imidazopyridazine compounds
3-(4-chloro-3-fluorophenyl)-N-ethylimidazo[1,2-b]pyridazine-2-carboxamide	IC50	25.8 nM	US-10077269: Imidazopyridazine compounds
3-(4-Chlorophenyl)-N-cyclopropylimidazo[1,2-b]pyridazine-2-carboxamide (2)	IC50	27.9 nM	US-10077269: Imidazopyridazine compounds
3-(4-chloro-2,5-difluorophenyl)-N-ethylimidazo[1,2-b]pyridazine-2-carboxamide	IC50	29.2 nM	US-10077269: Imidazopyridazine compounds
3-(4-chlorophenyl)-N-[(1R,2S)-2-fluorocyclopro-pyl]imidazo[1,2-b]pyridazine-2-carboxamide	IC50	39.3 nM	US-10077269: Imidazopyridazine compounds
azetidin-1-yl-[3-(3,4-dichlorophenyl)imidazo[1,2-b]pyridazin-2-yl]methanone	IC50	40 nM	US-10077269: Imidazopyridazine compounds
3-(4-cyano-2,5-difluorophenyl)-N-cyclopropylimidazo[1,2-b]pyridazine-2-carboxamide	IC50	42.5 nM	US-10077269: Imidazopyridazine compounds
3-(4-chloro-3-fluorophenyl)-N-(1H-pyrazol-4-yl)imidazo[1,2-b]pyridazine-2-carboxamide	IC50	43.4 nM	US-10077269: Imidazopyridazine compounds
azetidin-1-yl-[3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-2-yl]methanone	IC50	44.4 nM	US-10077269: Imidazopyridazine compounds
3-(4-chlorophenyl)-N-ethylimidazo[1,2-b]pyridazine-2-carboxamide	IC50	47.2 nM	US-10077269: Imidazopyridazine compounds
(R)-(-)-3-{2-[(3-cyclopropyloxy-4-difluromethoxy)phenyl]-2-[5-(2-(1-hydroxy-1-trifluoromethyl-2,2,2-trifluoro)ethyl)thiazolyl]ethyl}pyridine N-Oxide	IC50	56 nM
3-(4-chloro-2-fluorophenyl)-N-cyclopropylimidazo[1,2-b]pyridazine-2-carboxamide	IC50	58.1 nM	US-10077269: Imidazopyridazine compounds
4-[2-(azetidin-1-ylcarbonyl)imidazo[1,2-b]pyridazin-3-yl]-2,5-difluorobenzonitrile	IC50	59.7 nM	US-10077269: Imidazopyridazine compounds
CHEMBL59269	IC50	103 nM
3-(4-cyano-5-fluoro-2-methylphenyl)-N-ethylimidazo[1,2-b]pyridazine-2-carboxamide	IC50	107 nM	US-10077269: Imidazopyridazine compounds
3-(5-chloropyridin-3-yl)-N-cyclopropylimidazo[1,2-b]pyridazine-2-carboxamide	IC50	108 nM	US-10077269: Imidazopyridazine compounds
3-(4-chlorophenyl)-N-propyl-imidazo[1,2-b]pyridazine-2-carboxamide	IC50	111 nM	US-10077269: Imidazopyridazine compounds
azetidin-1-yl-[3-(4-chloro-2-fluorophenyl)imidazo[1,2-b]pyridazin-2-yl]methanone	IC50	113 nM	US-10077269: Imidazopyridazine compounds
3-(3-chloro-4-methylphenyl)-N-[(1R,2S)-2-fluorocyclopro-pyl]imidazo[1,2-b]pyridazine-2-carboxamide	IC50	113 nM	US-10077269: Imidazopyridazine compounds
[3-(4-chlorophenyl)imidazo[1,2-b]pyridazin-2-yl]-(3,3-difluoroazetidin-1-yl)methanone	IC50	126 nM	US-10077269: Imidazopyridazine compounds
CHEMBL86158	IC50	126 nM
3-(4-chlorophenyl)-N-(1-methylcyclopropyl)imidazo[1,2-b]pyridazine-2-carboxamide	IC50	127 nM	US-10077269: Imidazopyridazine compounds
3-(4-chloro-2,5-difluorophenyl)-N-methylimidazo[1,2-b]pyridazine-2-carboxamide	IC50	134 nM	US-10077269: Imidazopyridazine compounds
azetidin-1-yl-[3-(2-fluoro-4-methylphenyl)imidazo[1,2-b]pyridazin-2-yl]methanone	IC50	136 nM	US-10077269: Imidazopyridazine compounds
(6S)-3-(4-chloro-5-fluoro-2-methylphenyl)-N-cyclopropyl-6-fluoro-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide	IC50	136 nM	US-10323042: 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide compounds
3-(4-cyano-5-fluoro-2-methylphenyl)-N-propan-2-ylimidazo[1,2-b]pyridazine-2-carboxamide	IC50	138 nM	US-10077269: Imidazopyridazine compounds
3-(4-chloro-3,5-difluorophenyl)-N-cyclopropylimidazo[1,2-b]pyridazine-2-carboxamide	IC50	145 nM	US-10077269: Imidazopyridazine compounds
4-[2-(azetidin-1-ylcarbonyl)imidazo[1,2-b]pyridazin-3-yl]-5-fluoro-2-methylbenzonitrile	IC50	147 nM	US-10077269: Imidazopyridazine compounds
3-(4-chloro-5-fluoro-2-methylphenyl)-N-methyl-imidazo[1,2-b]pyridazine-2-carboxamide	IC50	150 nM	US-10077269: Imidazopyridazine compounds
azetidin-1-yl-[3-(4-fluoro-3,5-dimethylphenyl)imidazo[1,2-b]pyridazin-2-yl]methanone	IC50	153 nM	US-10077269: Imidazopyridazine compounds
3-(4-chloro-2,5-difluorophenyl)-N-cyclopropyl-6,6-difluoro-5,7-dihydropyrazolo[5,1-b][1,3]oxazine-2-carboxamide	IC50	156 nM	US-10323042: 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide compounds
N-(bicyclo[1.1.1]pent-1-yl)-3-(4-chlorophenyl)imidazo[1,2-b]pyridazine-2-carboxamide	IC50	161 nM	US-10077269: Imidazopyridazine compounds
3-(4-chloro-3-fluorophenyl)-N-cyclopropyl-N-methyl-imidazo[1,2-b]pyridazine-2-carboxamide	IC50	170 nM	US-10077269: Imidazopyridazine compounds

ChEMBL bioactivities

2325 potent at pChembl≥5 of 2672 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.60	IC50	0.02512	nM	CHEMBL5417689
10.59	IC50	0.026	nM	TRANIMILAST
10.52	IC50	0.03	nM	CHEMBL3113966
10.52	IC50	0.03	nM	CHEMBL3113954
10.52	IC50	0.03	nM	CHEMBL3113949
10.52	IC50	0.03	nM	CHEMBL3113948
10.52	IC50	0.03	nM	CHEMBL3968147
10.40	IC50	0.04	nM	CHEMBL3113943
10.40	IC50	0.04	nM	CHEMBL3113976
10.40	IC50	0.04	nM	TRANIMILAST
10.40	IC50	0.04	nM	CHEMBL3113968
10.40	IC50	0.04	nM	CHEMBL3113962
10.30	IC50	0.05	nM	CHEMBL3113964
10.30	IC50	0.05	nM	CHEMBL3113953
10.30	IC50	0.05	nM	CHEMBL3113950
10.30	IC50	0.05	nM	CHEMBL3113946
10.30	IC50	0.05	nM	CHEMBL3113943
10.30	IC50	0.05	nM	CHEMBL380321
10.30	IC50	0.05	nM	CHEMBL4800045
10.29	IC50	0.051	nM	CHEMBL65426
10.22	IC50	0.06	nM	CHEMBL3113976
10.22	IC50	0.06	nM	TRANIMILAST
10.22	IC50	0.06	nM	CHEMBL3113967
10.22	IC50	0.06	nM	CHEMBL3113955
10.22	IC50	0.06	nM	CHEMBL3113951
10.15	IC50	0.07	nM	CHEMBL3113978
10.15	IC50	0.07	nM	CHEMBL371037
10.14	IC50	0.072	nM	CHEMBL3113937
10.10	IC50	0.08	nM	CHEMBL67668
10.10	IC50	0.08	nM	CHEMBL3113963
10.10	IC50	0.08	nM	CHEMBL3113947
10.10	IC50	0.08	nM	CHEMBL3113945
10.05	IC50	0.09	nM	CHEMBL3113958
10.05	IC50	0.09	nM	CHEMBL199015
10.00	IC50	0.1	nM	CHEMBL3113939
10.00	IC50	0.1	nM	CHEMBL5081214
9.96	IC50	0.11	nM	CHEMBL3113958
9.92	IC50	0.12	nM	CHEMBL3113978
9.92	IC50	0.12	nM	CHEMBL3113975
9.92	IC50	0.12	nM	CHEMBL197392
9.92	IC50	0.12	nM	CHEMBL196969
9.90	IC50	0.1259	nM	CHEMBL5080391
9.89	IC50	0.13	nM	T-2585.HCL
9.89	IC50	0.13	nM	CHEMBL3113977
9.89	IC50	0.13	nM	CHEMBL3113950
9.89	IC50	0.13	nM	CHEMBL3113975
9.85	IC50	0.14	nM	CHEMBL3113942
9.85	IC50	0.14	nM	CHEMBL371089
9.82	IC50	0.15	nM	CHEMBL3113961
9.80	IC50	0.16	nM	CHEMBL552877

PubChem BioAssay actives

1974 with measured affinity, of 3562 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3-ethoxy-4-methoxyphenyl)ethyl] 5-[[[(2S)-1-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]-3-hydroxy-1-oxo-2-phenylpropan-2-yl]amino]methyl]thiophene-2-carboxylate	2011005: Inhibition of human recombinant PDE4C2 expressed in baculovirus expression system using cAMP as substrate by radiometric assay	ic50	<0.0001	uM
3-[3-[5-[(3,5-dichloro-4-pyridinyl)carbamoylamino]-1-ethyl-6-oxopyridazin-3-yl]phenyl]-N-[7-[2-hydroxyethyl(methyl)amino]heptyl]benzamide	1720034: Inhibition of PDE4 (unknown origin) expressed in Saccharomyces cerevisiae using [3H] cAMP as substrate incubated for 1 hr by scintillation proximity assay	ic50	<0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-(cyclopropylmethoxy)-4-(methanesulfonamido)benzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	<0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-(methanesulfonamido)-4-methylbenzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	<0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-(cyclopropylmethoxy)-4-methoxybenzoate	1068845: Inhibition of PDE4 activity in human PBMC assessed as inhibition of LPS-induced TNFalpha release after 18 hrs by ELISA	ic50	<0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-(dimethylsulfamoyl)-4-methoxybenzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	<0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-(cyclopropylmethoxy)-4-hydroxybenzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	<0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-(hydroxymethyl)-4-(methanesulfonamido)benzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	<0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 5-(methanesulfonamido)-2-methoxybenzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	<0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-(methanesulfonamido)-4-methoxybenzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	<0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 4-methoxy-3-(methylsulfamoyl)benzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	<0.0001	uM
6-[3-(dimethylcarbamoyl)phenyl]sulfonyl-4-(3-methoxyanilino)-8-methylquinoline-3-carboxamide	1720022: Inhibition of human PDE4 expressed in Saccharomyces cerevisiae preincubated for 30 mins followed by cAMP substrate addition	ic50	<0.0001	uM
(E)-3-[3-[6-(2-cyanopropan-2-yl)quinolin-8-yl]phenyl]-2-(4-methylsulfonylphenyl)-N-propan-2-ylprop-2-enamide	257450: Inhibition of LPS-induced TNFalpha production in human whole blood	ic50	0.0001	uM
2-[4-cyano-4-[3-cyclopentyloxy-4-(difluoromethoxy)phenyl]piperidin-1-yl]-N-hydroxyacetamide	159794: Inhibition of phosphodiesterase 4 (PDE4) prepared from human U937 cells	ic50	0.0001	uM
1-[[3-[6-(2-cyanopropan-2-yl)quinolin-8-yl]phenyl]methyl]-1-(4-methylsulfonylphenyl)-3-phenylurea	264625: Inhibition of human GST-PDE4C	ic50	0.0001	uM
8-[3-[(E)-2-(5-methyl-2-pyridinyl)-2-(4-methylsulfonylphenyl)ethenyl]phenyl]-6-propan-2-ylquinoline	257450: Inhibition of LPS-induced TNFalpha production in human whole blood	ic50	0.0001	uM
2-[5-[(1S)-1-[3-cyclopropyloxy-4-(difluoromethoxy)phenyl]-2-(1-oxidopyridin-1-ium-3-yl)ethyl]-1,3-thiazol-2-yl]-1,1,1,3,3,3-hexafluoropropan-2-ol	257450: Inhibition of LPS-induced TNFalpha production in human whole blood	ic50	0.0001	uM
5-[5-[(3,5-dichloro-4-pyridinyl)carbamoylamino]-1-ethyl-6-oxopyridazin-3-yl]-3-N-[3-(dimethylamino)propyl]-1-N-ethylbenzene-1,3-dicarboxamide	1720034: Inhibition of PDE4 (unknown origin) expressed in Saccharomyces cerevisiae using [3H] cAMP as substrate incubated for 1 hr by scintillation proximity assay	ic50	0.0001	uM
2-[(E)-1-(4-methylsulfonylphenyl)-2-[3-(6-propan-2-ylquinolin-8-yl)phenyl]ethenyl]-1,3-thiazole	257450: Inhibition of LPS-induced TNFalpha production in human whole blood	ic50	0.0001	uM
(E)-2-(4-methylsulfonylphenyl)-N-propan-2-yl-3-[3-(6-propan-2-ylquinolin-8-yl)phenyl]prop-2-enamide	257450: Inhibition of LPS-induced TNFalpha production in human whole blood	ic50	0.0001	uM
2-[4-[6,7-diethoxy-2,3-bis(hydroxymethyl)naphthalen-1-yl]-2-pyridinyl]-4-pyridin-3-ylphthalazin-1-one;hydrochloride	159633: Inhibition of guinea pig lung Phosphodiesterase 4	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 4-(methanesulfonamido)-3-methylbenzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 4-(cyclopropylmethoxy)-3-(methanesulfonamido)benzoate	1068845: Inhibition of PDE4 activity in human PBMC assessed as inhibition of LPS-induced TNFalpha release after 18 hrs by ELISA	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-(cyclopropylmethoxy)-4-(hydroxymethyl)benzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-(cyclopropylmethoxy)-5-(methanesulfonamido)benzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 4-(methanesulfonamido)benzoate	1068845: Inhibition of PDE4 activity in human PBMC assessed as inhibition of LPS-induced TNFalpha release after 18 hrs by ELISA	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-(methanesulfonamido)-5-methoxybenzoate	1068845: Inhibition of PDE4 activity in human PBMC assessed as inhibition of LPS-induced TNFalpha release after 18 hrs by ELISA	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] benzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-acetyloxy-4-methoxybenzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3,4-dimethoxybenzoate	1068845: Inhibition of PDE4 activity in human PBMC assessed as inhibition of LPS-induced TNFalpha release after 18 hrs by ELISA	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 4-(methanesulfonamido)-3-methoxybenzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 4-(methanesulfonamido)-2-methoxybenzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	0.0001	uM
2-(cyclopropylmethoxy)-4-[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethoxy]carbonylbenzoic acid	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 4-methylbenzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-hydroxy-4-methoxybenzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-acetamido-4-methoxybenzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 4-methoxybenzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 4-amino-3-(cyclopropylmethoxy)benzoate	1068845: Inhibition of PDE4 activity in human PBMC assessed as inhibition of LPS-induced TNFalpha release after 18 hrs by ELISA	ic50	0.0001	uM
[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-(cyclopropylmethoxy)-4-(cyclopropylsulfonylamino)benzoate	1068846: Inhibition of PDE4 isolated from human U937 cells assessed as reduction in cAMP level by LANCE assay	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
2-[4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)piperidin-1-yl]-N-hydroxyacetamide	159794: Inhibition of phosphodiesterase 4 (PDE4) prepared from human U937 cells	ic50	0.0001	uM
(Z)-3-[3-[6-(2-cyanopropan-2-yl)quinolin-8-yl]phenyl]-2-(4-methylsulfonylphenyl)-N-propan-2-ylprop-2-enamide	257450: Inhibition of LPS-induced TNFalpha production in human whole blood	ic50	0.0002	uM
2-[4-cyano-4-(3-cyclobutyloxy-4-methoxyphenyl)piperidin-1-yl]-N-hydroxyacetamide	159794: Inhibition of phosphodiesterase 4 (PDE4) prepared from human U937 cells	ic50	0.0002	uM
8-[3-[2-cyclopropylsulfonyl-2-fluoro-2-(4-methylsulfonylphenyl)ethyl]phenyl]-6-(2-methylsulfonylpropan-2-yl)quinoline	447673: Inhibition of human PDE4	ic50	0.0002	uM
3-methyl-5-[(Z)-1-(4-methylsulfonylphenyl)-2-[3-[6-(2-methylsulfonylpropan-2-yl)quinolin-8-yl]phenyl]ethenyl]-1,2,4-oxadiazole	257450: Inhibition of LPS-induced TNFalpha production in human whole blood	ic50	0.0002	uM
1,1-dicyclopropyl-2-fluoro-2-(4-methylsulfonylphenyl)-3-[3-[6-(2-methylsulfonylpropan-2-yl)quinolin-8-yl]phenyl]propan-1-ol	447673: Inhibition of human PDE4	ic50	0.0002	uM
5-[4-[2,3-bis(hydroxymethyl)-6,7-dimethoxynaphthalen-1-yl]-2-pyridinyl]phenanthridin-6-one	159634: In vitro inhibition of Phosphodiesterase 4 from guinea pig lung	ic50	0.0002	uM
[2-(3,5-dichloro-4-pyridinyl)-1-(3,4-dimethoxyphenyl)ethyl] 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoate	1720007: Inhibition of PDE4 (unknown origin)	ic50	0.0002	uM
2-[4-[7-ethoxy-2,3-bis(hydroxymethyl)-6-methoxynaphthalen-1-yl]-2-pyridinyl]-4-pyridin-3-ylphthalazin-1-one;hydrochloride	159634: In vitro inhibition of Phosphodiesterase 4 from guinea pig lung	ic50	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	4
Aflatoxin B1	affects expression, increases expression	4
Estradiol	affects cotreatment, decreases expression, affects binding, increases expression	3
bisphenol A	increases expression, decreases expression	2
chloropicrin	increases expression	2
Acetaminophen	increases expression	2
Cisplatin	affects cotreatment, increases expression, affects expression	2
Formaldehyde	decreases expression, increases expression	2
Valproic Acid	decreases expression, increases methylation	2
arsenite	increases methylation	1
sodium arsenite	affects methylation	1
benzo(e)pyrene	decreases methylation	1
trequinsin	decreases activity	1
CGP 52608	affects binding, increases reaction	1
Roflumilast	decreases activity	1
Cilomilast	decreases activity	1
NVP ABE171	decreases activity	1
L-826,141	decreases activity	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
pyrimidifen	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
bisphenol S	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
PF-04254644	decreases activity	1
picoxystrobin	decreases expression	1
Vorinostat	decreases expression	1
Panobinostat	affects cotreatment, affects expression	1
Arsenic	affects expression	1
Dactinomycin	affects cotreatment, increases expression	1

ChEMBL screening assays

498 unique, capped per target: 469 binding, 23 functional, 6 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000405	Binding	Inhibition of PDE4 in human lung	Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease. — J Med Chem
CHEMBL4348839	ADMET	Inhibition of PDE4 (unknown origin)	Structure Overhaul Affords a Potent Purine PI3Kδ Inhibitor with Improved Tolerability. — J Med Chem
CHEMBL682878	Functional	PDE4-related emetic activity in ferrets after intravenous administration at 10 mg/kg	Synthesis, structure-activity relationships, and pharmacological profile of 9-amino-4-oxo-1-phenyl-3,4,6,7-tetrahydro[1,4]diazepino[6, 7,1-hi]indoles: discovery of potent, selective phosphodiesterase type 4 inhibitors. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0U4	ACTOne cAMP-PDE4C	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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