ADCY5

Summary

ADCY5 (adenylate cyclase 5, HGNC:236) is a protein-coding gene on chromosome 3q21.1, encoding Adenylate cyclase type 5 (O95622). Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.

This gene encodes a member of the membrane-bound adenylyl cyclase enzymes. Adenylyl cyclases mediate G protein-coupled receptor signaling through the synthesis of the second messenger cAMP. Activity of the encoded protein is stimulated by the Gs alpha subunit of G protein-coupled receptors and is inhibited by protein kinase A, calcium and Gi alpha subunits. Single nucleotide polymorphisms in this gene may be associated with low birth weight and type 2 diabetes. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene.

Source: NCBI Gene 111 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dyskinesia with orofacial involvement (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 72
• Clinical variants (ClinVar): 968 total — 31 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 49
• Druggable target: yes
• MANE Select transcript: NM_183357

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:236
Approved symbol	ADCY5
Name	adenylate cyclase 5
Location	3q21.1
Locus type	gene with protein product
Status	Approved
Aliases	AC5
Ensembl gene	ENSG00000173175
Ensembl biotype	protein_coding
OMIM	600293
Entrez	111

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000309879, ENST00000462833, ENST00000466617, ENST00000468683, ENST00000470367, ENST00000474577, ENST00000476455, ENST00000478092, ENST00000483566, ENST00000491190, ENST00000699714, ENST00000699715, ENST00000699716, ENST00000699717, ENST00000699718, ENST00000699719, ENST00000850916

RefSeq mRNA: 3 — MANE Select: NM_183357 NM_001199642, NM_001378259, NM_183357

CCDS: CCDS3022, CCDS56274, CCDS93353

Canonical transcript exons

ENST00000462833 — 21 exons

Exon	Start	End
ENSE00001205221	123286685	123286809
ENSE00001205223	123289750	123289954
ENSE00001205243	123318020	123318117
ENSE00001205246	123319674	123319818
ENSE00001205260	123332564	123332675
ENSE00001205278	123327618	123327759
ENSE00001222625	123296084	123296216
ENSE00001222632	123297353	123297382
ENSE00001222674	123320749	123320771
ENSE00001222681	123325322	123325462
ENSE00001222692	123328644	123328802
ENSE00001222702	123330889	123331016
ENSE00001762441	123291113	123291376
ENSE00001765048	123447412	123449090
ENSE00001867315	123282296	123284736
ENSE00003461679	123347782	123347903
ENSE00003496821	123314235	123314322
ENSE00003544138	123352432	123352581
ENSE00003619223	123304067	123304183
ENSE00003668477	123303055	123303219
ENSE00003681321	123300120	123300295

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 97.38.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7870 / max 156.7478, expressed in 330 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44163	0.8641	181
44165	0.3306	143
44164	0.2403	83
44162	0.1358	82
44157	0.1010	48
44161	0.0584	18
44156	0.0568	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.38	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.08	gold quality
lower esophagus	UBERON:0013473	97.01	gold quality
mucosa of stomach	UBERON:0001199	96.75	gold quality
right coronary artery	UBERON:0001625	96.69	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.65	gold quality
popliteal artery	UBERON:0002250	96.16	gold quality
tibial artery	UBERON:0007610	96.14	gold quality
right atrium auricular region	UBERON:0006631	95.45	gold quality
heart left ventricle	UBERON:0002084	95.38	gold quality
putamen	UBERON:0001874	95.23	gold quality
nucleus accumbens	UBERON:0001882	95.23	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.16	gold quality
aorta	UBERON:0000947	95.15	gold quality
cardiac atrium	UBERON:0002081	94.99	gold quality
descending thoracic aorta	UBERON:0002345	94.97	gold quality
caudate nucleus	UBERON:0001873	94.88	gold quality
cardiac ventricle	UBERON:0002082	94.77	gold quality
thoracic aorta	UBERON:0001515	94.10	gold quality
ascending aorta	UBERON:0001496	93.98	gold quality
heart	UBERON:0000948	93.79	gold quality
left coronary artery	UBERON:0001626	93.72	gold quality
coronary artery	UBERON:0001621	93.02	gold quality
left ventricle myocardium	UBERON:0006566	92.60	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.45	gold quality
cortical plate	UBERON:0005343	92.13	gold quality
prefrontal cortex	UBERON:0000451	90.88	gold quality
anterior cingulate cortex	UBERON:0009835	89.72	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.67	gold quality
right frontal lobe	UBERON:0002810	89.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting ADCY5, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-154-5P	98.92	66.65	733
HSA-MIR-181A-2-3P	98.91	67.60	1168

Literature-anchored findings (GeneRIF, showing 40)

• Identification of RGS2 and type V adenylyl cyclase interaction sites. (PMID:12604604)
• Adenylyl cyclase V and adenylyl cyclase VI interacts with A-kinase anchoring protein 79 (AKAP79) in a complex that associates with protein kinase A forming a negative feedback loop that termporally regulates cAMP production. (PMID:16973443)
• G protein betagamma subunits stimulate type V and VI adenylyl cyclases (PMID:17110384)
• variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight (PMID:20372150)
• Data report a novel association between the fetal ADCY5 type 2 diabetes risk allele and decreased birthweight, and confirm in meta-analyses associations between decreased birthweight and the type 2 diabetes risk alleles of HHEX-IDE and CDKAL1. (PMID:20490451)
• a genetic variant of adcy5 leads to asymmetric growth restriction, characterized by a relatively larger head circumference, from third trimester (PMID:21307140)
• Data show low birth weight in Asian Indians is not due to variation near CCNL1/ADCY5, but variant ADCY5 is associated with elevated glucose/decreased insulin response which suggests a common genetic cause of low birth weight and risk of type 2 diabetes. (PMID:21712988)
• The role of four loci (ADCY5, GIPR, GCKR and VPS13C) in early impairment of glucose and insulin metabolism in children, was investigated. (PMID:21789219)
• The SNP in ADCY5 is implicated in defective proinsulin-to-insulin conversion and previous findings on the role of a genetic variant in MADD on proinsulin-to-insulin conversion, were confirmed. (PMID:21887289)
• Alleles of single nucleotide polymorphisms in GLIS3 and ADCY5 may confer risk of type 2 diabetes. (PMID:21949744)
• results demonstrate a crosstalk between two metabotropic and one ionotropic purinergic receptor that regulates cAMP levels through adenylate cyclase 5 and modulates axonal elongation triggered by neurotropic factors and the PI3K-Akt-GSK3 pathway (PMID:22250198)
• no detectable effect (with an OR >2.1) of the variants in GCKR, GIPR, ADCY5 and VPS13C on the response to sulfonylurea treatment, indicating that these variants are not significantly contributing to the risk of SH in patients with T2D (PMID:22956255)
• Polymorphisms ADCY5 are associated with an alcohol-dependent phenotype in females, which is distinguished by comorbid signs of depression. (PMID:23278386)
• AC5, by binding active Galphai1, interferes with G-protein deactivation and reassembly and thereby might sensitize its own regulation. (PMID:23841650)
• the functional effect of missense mutations in adenylyl cyclase 5 (ADCY5) in sporadic and inherited cases of autosomal dominant familial dyskinesia with facial myokymia (PMID:24700542)
• Alterations in beta-cell ADCY5 expression and impaired glucose signaling thus provide a likely route through which ADCY5 gene polymorphisms influence fasting glucose levels and T2D risk, while exerting more minor effects on incretin action (PMID:24740569)
• LRs are essential not only for the proper membrane distribution and maintenance of AC5/6 activity but also for the regulation of D1R- and D5R-mediated AC signaling. (PMID:25049074)
• This study identification of ADCY5 mutations in one family with dyskinesia-facial myokymia and in two unrelated sporadic cases of paxoysmal choreic/dystonia-facial myokymia. (PMID:25545163)
• changes in adipose tissue ADCY5 expression are related to obesity and fat distribution. (PMID:25793868)
• these results suggest that AnxA4 is a novel direct negative regulator of AC5, adding a new facet to the functions of annexins. (PMID:26023182)
• Mutations in ADCY5 were linked to benign hereditary chorea. (PMID:26085604)
• This study showed that ADCY5 mutation carriers display pleiotropic paroxysmal day and nighttime dyskinesias.( (PMID:26686870)
• Risk alleles for 6 loci increased glucose levels from birth to 5 years of age (ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2 (PMID:27049325)
• ADCY5 gene mutations can present with a wider variety of movement disorder syndromes. (PMID:27061943)
• This study demonstrated that whole-exome sequencing show reveled ADCY5 mutation with early-onset generalized dystonia. (PMID:27666935)
• the clinical spectrum of ADCY5 mutations encompasses paroxysmal weakness in addition to paroxysmal dyskinesia and persistent hyperkinesia, nominating ADCY5 mutations as a genetic cause of unexplained alternating hemiplegia of childhood. (PMID:27931826)
• ADCY5-related dyskinesia may manifest variable expressivity within a single family, and affected individuals may be initially diagnosed with differing neurological phenotypes. (PMID:28229249)
• In this series of five ADCY5 mutation carriers, perioral twitches and truncal jerks do not represent myokymia (PMID:28442302)
• Mutations in ADCY5 are responsible for a hyperkinetic movement disorder that can be preceded by episodic attacks before the movement disorder becomes persistent and is frequently misdiagnosed as dyskinetic cerebral palsy. (PMID:28511835)
• These data suggest that rs11708067-A risk allele contributes to type 2 diabetes by disrupting an islet enhancer, which results in reduced ADCY5 expression and impaired insulin secretion. (PMID:28684635)
• ADCY5, which encodes adenylyl cyclase type 5, and RAP2C, which encodes a member of the RAS oncogene family, had associations of nearly genomewide significance. ADCY5 locus have been reported to be associated with birth weight and type 2 diabetes however, none were in linkage disequilibrium with the SNPs showing significant association with gestational duration. (PMID:28877031)
• Oculomotor apraxia and disrupted sleep with nocturnal ballistic bouts in ADCY5 mutation-related dyskinesia. (PMID:29680308)
• Depression and psychosis are described as a part of the ADCY5-related dyskinesia phenotypic spectrum. (PMID:30172639)
• indicate an association between PDE10A and ADCY5 mutations and pre/postsynaptic molecular changes, substantia nigra damage, and white and gray matter changes within the striatocortical pathways (PMID:30345538)
• we describe a native Arabian Bedouin family with an autosomal recessive ADCY5-related disorder (PMID:30975617)
• Sleep in ADCY5-Related Dyskinesia: Prolonged Awakenings Caused by Abnormal Movements. (PMID:31383240)
• Clinical diagnostic exome sequencing in dystonia: Genetic testing challenges for complex conditions. (PMID:31628766)
• Three SNPs (rs6797915, rs9856662 and rs9875803) displayed evidence for association with plasma glucose 1 hour after a 50-gram glucose challenge test, one (rs6777397) displayed evidence for association with HOMA1-beta, and one (rs6762009) displayed evidence for association with HOMA1-IR. (PMID:32163478)
• Deep brain stimulation reduces (nocturnal) dyskinetic exacerbations in patients with ADCY5 mutation: a case series. (PMID:32647899)
• Galphai1 inhibition mechanism of ATP-bound adenylyl cyclase type 5. (PMID:33493164)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adcy5	ENSDARG00000091342
mus_musculus	Adcy5	ENSMUSG00000022840
rattus_norvegicus	Adcy5	ENSRNOG00000002229
drosophila_melanogaster	CG43373	FBGN0263131

Paralogs (17): GUCY1B1 (ENSG00000061918), GUCY2C (ENSG00000070019), ADCY2 (ENSG00000078295), GUCY2F (ENSG00000101890), NPR3 (ENSG00000113389), ADCY7 (ENSG00000121281), ADCY4 (ENSG00000129467), GUCY2D (ENSG00000132518), ADCY3 (ENSG00000138031), GUCY1A2 (ENSG00000152402), ADCY8 (ENSG00000155897), NPR2 (ENSG00000159899), ADCY9 (ENSG00000162104), GUCY1A1 (ENSG00000164116), ADCY1 (ENSG00000164742), NPR1 (ENSG00000169418), ADCY6 (ENSG00000174233)

Protein

Protein identifiers

Adenylate cyclase type 5 — O95622 (reviewed: O95622)

Alternative names: ATP pyrophosphate-lyase 5, Adenylate cyclase type V, Adenylyl cyclase 5

All UniProt accessions (7): O95622, A0A384P5Q5, A0A8V8TNW3, A0A8V8TP58, B3KWA8, C9JRT8, F8WBM0

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Mediates signaling downstream of ADRB1. Regulates the increase of free cytosolic Ca(2+) in response to increased blood glucose levels and contributes to the regulation of Ca(2+)-dependent insulin secretion.

Subunit / interactions. Interacts with GNAS, GNB1 and GNG2. Part of a complex containing AKAP5, ADCY6, PDE4C and PKD2. Interacts with RAF1.

Subcellular location. Cell membrane. Cell projection. Cilium.

Tissue specificity. Detected in pancreas islets (at protein level). Expressed in the brain, with high expression in the corpus striatum.

Post-translational modifications. Phosphorylated by RAF1.

Disease relevance. Dyskinesia with orofacial involvement, autosomal recessive (DSKOR) [MIM:619647] An autosomal recessive disorder characterized by abnormal involuntary movements mainly affecting the limbs and causing walking difficulties, oro-facial dyskinesia, and speech delay. Some patients develop neuropsychiatric features. Cardiomyopathy has rarely been described and may be a manifestation of the disorder. The disease is caused by variants affecting the gene represented in this entry. Dyskinesia with orofacial involvement, autosomal dominant (DSKOD) [MIM:606703] A disorder characterized by predominantly perioral and periorbital myokymia, and face, neck and upper limb dystonic/choreic movements. Initially paroxysmal and worsened by stress, the dyskinetic episodes become nearly constant by the end of the third decade of life, but in some individuals, they may diminish in frequency and severity at older ages. The disease is caused by variants affecting the gene represented in this entry. Neurodevelopmental disorder with hyperkinetic movements and dyskinesia (NEDHYD) [MIM:619651] An autosomal recessive disorder characterized by severe global developmental delay, axial hypotonia, impaired intellectual development, poor overall growth, and abnormal involuntary hyperkinetic movements. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by G(s) G alpha protein GNAS. Inhibited by G(i) G alpha protein GNAI1. Activity is further increased by interaction with the G-protein beta and gamma subunit complex formed by GNB1 and GNG2. Activated by forskolin. Is not activated by calmodulin. Inhibited by adenosine and ATP analogs. Inhibited by calcium ions, already at micromolar concentrations. Phosphorylation by RAF1 results in its activation.

Cofactor. Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).

Domain organisation. The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain.

Similarity. Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O95622-1	1	yes
O95622-2	2

RefSeq proteins (3): NP_001186571, NP_001365188, NP_899200* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001054	A/G_cyclase	Domain
IPR009398	Adcy_conserved_dom	Domain
IPR018297	A/G_cyclase_CS	Conserved_site
IPR029787	Nucleotide_cyclase	Homologous_superfamily
IPR030672	Adcy	Family
IPR032628	AC_N	Domain

Pfam: PF00211, PF06327, PF16214

Enzyme classification (BRENDA):

• EC 4.6.1.1 — adenylate cyclase (BRENDA: 120 organisms, 167 substrates, 404 inhibitors, 155 Km, 27 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0005–8.78	135
MGATP2-	0.009–2.2	4
MNATP2-	0.067–0.086	2
ADENYLIMIDODIPHOSPHATE	0.33	1
CAMP	14	1
DATP	0.44	1
DEOXYCAMP	13	1
DIPHOSPHATE	1.9	1
GTP	1.38	1

Catalyzed reactions (Rhea), 1 shown:

• ATP = 3’,5’-cyclic AMP + diphosphate (RHEA:15389)

UniProt features (53 total): transmembrane region 12, binding site 12, sequence variant 7, modified residue 6, topological domain 4, compositionally biased region 4, domain 2, glycosylation site 2, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8SL3	ELECTRON MICROSCOPY	7
8SL4	ELECTRON MICROSCOPY	7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95622-F1	73.91	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (12): 474–479; 474; 474; 475; 516–518; 518; 518; 562; 1123; 1197–1199; 1204–1208; 1244

Post-translational modifications (6): 23, 96, 155, 666, 754, 1011

Glycosylation sites (2): 870, 887

Function

Pathways and Gene Ontology

Reactome pathways

49 pathways

ID	Pathway
R-HSA-163359	Glucagon signaling in metabolic regulation
R-HSA-163615	PKA activation
R-HSA-164378	PKA activation in glucagon signalling
R-HSA-170660	Adenylate cyclase activating pathway
R-HSA-170670	Adenylate cyclase inhibitory pathway
R-HSA-381676	Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-400042	Adrenaline,noradrenaline inhibits insulin secretion
R-HSA-418555	G alpha (s) signalling events
R-HSA-418594	G alpha (i) signalling events
R-HSA-418597	G alpha (z) signalling events
R-HSA-432040	Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-5610787	Hedgehog ‘off’ state
R-HSA-9634597	GPER1 signaling
R-HSA-9660821	ADORA2B mediated anti-inflammatory cytokines production
R-HSA-9664323	FCGR3A-mediated IL10 synthesis
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-111885	Opioid Signalling
R-HSA-111931	PKA-mediated phosphorylation of CREB
R-HSA-111933	Calmodulin induced events
R-HSA-111996	Ca-dependent events
R-HSA-111997	CaM pathway
R-HSA-112040	G-protein mediated events
R-HSA-112043	PLC beta mediated events
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1430728	Metabolism
R-HSA-1489509	DAG and IP3 signaling
R-HSA-162582	Signal Transduction
R-HSA-163685	Integration of energy metabolism

MSigDB gene sets: 314 (showing top): GOBP_G_PROTEIN_COUPLED_PURINERGIC_RECEPTOR_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_BEHAVIOR, GOBP_CELLULAR_RESPONSE_TO_LIPID, REACTOME_ADRENALINE_NORADRENALINE_INHIBITS_INSULIN_SECRETION, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_FLUID_SHEAR_STRESS, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_CAMP_BIOSYNTHETIC_PROCESS, GOBP_HORMONE_TRANSPORT, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CYCLIC_NUCLEOTIDE_METABOLIC_PROCESS

GO Biological Process (15): G protein-coupled adenosine receptor signaling pathway (GO:0001973), renal water homeostasis (GO:0003091), cAMP biosynthetic process (GO:0006171), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), adenylate cyclase-activating dopamine receptor signaling pathway (GO:0007191), adenylate cyclase-inhibiting dopamine receptor signaling pathway (GO:0007195), positive regulation of cytosolic calcium ion concentration (GO:0007204), locomotory behavior (GO:0007626), intracellular signal transduction (GO:0035556), neuromuscular process controlling balance (GO:0050885), regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061178), cellular response to glucagon stimulus (GO:0071377), vascular endothelial cell response to laminar fluid shear stress (GO:0097700), cellular response to forskolin (GO:1904322), cyclic nucleotide biosynthetic process (GO:0009190)

GO Molecular Function (8): adenylate cyclase activity (GO:0004016), ATP binding (GO:0005524), adenylate cyclase binding (GO:0008179), metal ion binding (GO:0046872), scaffold protein binding (GO:0097110), nucleotide binding (GO:0000166), lyase activity (GO:0016829), phosphorus-oxygen lyase activity (GO:0016849)

GO Cellular Component (4): plasma membrane (GO:0005886), cilium (GO:0005929), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
GPCR downstream signalling	3
G-protein mediated events	2
Regulation of insulin secretion	2
Anti-inflammatory response favouring Leishmania parasite infection	2
Integration of energy metabolism	1
PKA-mediated phosphorylation of CREB	1
Glucagon signaling in metabolic regulation	1
Activation of GABAB receptors	1
Aquaporin-mediated transport	1
Signaling by Hedgehog	1
G alpha (s) signalling events	1
Response of endothelial cells to shear stress	1
G alpha (i) signalling events	1
Calmodulin induced events	1
CaM pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled dopamine receptor signaling pathway	2
cellular anatomical structure	2
G protein-coupled purinergic receptor signaling pathway	1
renal system process	1
multicellular organismal-level water homeostasis	1
purine ribonucleotide biosynthetic process	1
cyclic nucleotide biosynthetic process	1
cAMP metabolic process	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
regulation of biological quality	1
behavior	1
intracellular anatomical structure	1
signal transduction	1
musculoskeletal movement	1
neuromuscular process	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion	1
regulation of cellular localization	1
response to glucagon	1
cellular response to peptide hormone stimulus	1
cellular response to laminar fluid shear stress	1
vascular endothelial cell response to fluid shear stress	1
cellular response to lipid	1
cellular response to alcohol	1
cellular response to ketone	1
response to forskolin	1
nucleotide biosynthetic process	1
cyclic nucleotide metabolic process	1
cyclase activity	1
phosphorus-oxygen lyase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
enzyme binding	1
cation binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1

Protein interactions and networks

STRING

1966 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADCY5	AKAP5	P24588	966
ADCY5	PRKACA	P17612	951
ADCY5	PKD2	Q13563	932
ADCY5	DGKB	Q9Y6T7	925
ADCY5	PRKACB	P22694	924
ADCY5	PRKACG	P22612	924
ADCY5	MTNR1B	P49286	912
ADCY5	PDE4C	Q08493	872
ADCY5	GIPR	P48546	827
ADCY5	RAPGEF3	O95398	809
ADCY5	G6PC2	Q9NQR9	793
ADCY5	CACNA1C	Q13936	771
ADCY5	CAV3	P56539	743
ADCY5	CDKAL1	Q5VV42	731
ADCY5	GCK	P35557	729

IntAct

5 interactions, top by confidence:

A	B	Type	Score
ADCY5	AK2	psi-mi:“MI:0915”(physical association)	0.400
ADCY5	TFRC	psi-mi:“MI:0915”(physical association)	0.400
	DDX3Y	psi-mi:“MI:0914”(association)	0.350
CACNG5		psi-mi:“MI:0914”(association)	0.350

BioGRID (21): ADCY5 (Affinity Capture-Western), RGS2 (Affinity Capture-Western), RGS2 (Reconstituted Complex), AK2 (Proximity Label-MS), TFRC (Proximity Label-MS), ADCY5 (Co-purification), ADCY5 (Two-hybrid), ADCY5 (Co-fractionation), ADCY5 (Affinity Capture-MS), LRP4 (Cross-Linking-MS (XL-MS)), ADCY5 (Protein-peptide), Mycbp2 (Two-hybrid), Gnb2 (Two-hybrid), Gnb1 (Reconstituted Complex), Gnb1 (Two-hybrid)

ESM2 similar proteins: A0A059XKS9, A0A125YS36, A0A125YYR0, A0A7J6K144, A0A7J6K629, A0A7J6K7I9, A0A7J6K7Y0, A0A7J6KE60, A0MQA3, A2YBX5, A4HK17, A4I7K1, B6KFA9, B9Q0C2, L7WGA7, O60503, O95622, P27116, P30803, P40144, P84309, Q02343, Q03343, Q04400, Q07762, Q0DCT8, Q0PKV7, Q2PP52, Q2QNS6, Q383A1, Q388F1, Q38CE9, Q39183, Q4CTY5, Q4D7L5, Q4DHA1, Q4Q5P8, Q57XV5, Q580W5, Q6GV23

Diamond homologs: A0A078BQP2, A0A0U1RPR8, A8WPG9, A8XQC7, B1Q257, E7EAU8, G5EEE9, G5EFQ0, H2L002, N1NVB7, O02298, O02740, O16544, O16715, O19179, O43306, O54865, O62026, O62179, O75343, O95622, P0A4Y1, P11528, P16065, P16066, P16067, P16068, P18293, P18910, P19686, P19687, P20594, P20595, P22717, P23897, P25092, P30803, P30804, P33402, P40144

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
NF1	up-regulates	ADCY5
GNAL	“up-regulates activity”	ADCY5	binding
GNB5	“down-regulates activity”	ADCY5	binding
ADCY5	“up-regulates quantity”	“3’,5’-cyclic AMP”	“chemical modification”
GNAZ	“down-regulates activity”	ADCY5	binding
GNB/GNG	“down-regulates activity”	ADCY5	binding
GNAI1	“down-regulates activity”	ADCY5	binding
GNAI2	“down-regulates activity”	ADCY5	binding
GNAI3	“down-regulates activity”	ADCY5	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	31
Likely pathogenic	28
Uncertain significance	409
Likely benign	297
Benign	113

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1188830	NM_183357.3(ADCY5):c.2080_2088del (p.Lys694_Met696del)	Pathogenic
1327477	NM_183357.3(ADCY5):c.3045C>A (p.Asp1015Glu)	Pathogenic
1327478	NM_183357.3(ADCY5):c.697T>C (p.Tyr233His)	Pathogenic
1327483	NM_183357.3(ADCY5):c.3712C>T (p.Arg1238Trp)	Pathogenic
1327484	NM_183357.3(ADCY5):c.1947+1G>T	Pathogenic
1452793	NM_183357.3(ADCY5):c.178dup (p.Ala60fs)	Pathogenic
152210	GRCh38/hg38 3q13.33-21.3(chr3:121925147-126782249)x1	Pathogenic
153722	GRCh38/hg38 3q13.31-21.2(chr3:114122562-124532374)x1	Pathogenic
155628	GRCh38/hg38 3q13.32-21.3(chr3:118673898-126540730)x1	Pathogenic
162090	NM_183357.3(ADCY5):c.1252C>T (p.Arg418Trp)	Pathogenic
162091	NM_183357.3(ADCY5):c.2176G>A (p.Ala726Thr)	Pathogenic
162092	NM_183357.3(ADCY5):c.3086T>A (p.Met1029Lys)	Pathogenic
1685503	NM_183357.3(ADCY5):c.2278C>T (p.Arg760Ter)	Pathogenic
2015778	NM_183357.3(ADCY5):c.1575del (p.Leu526fs)	Pathogenic
208485	NM_183357.3(ADCY5):c.2088+1G>T	Pathogenic
208670	NM_183357.3(ADCY5):c.1425C>G (p.Ile475Met)	Pathogenic
218354	NM_183357.3(ADCY5):c.1253G>A (p.Arg418Gln)	Pathogenic
218355	NM_183357.3(ADCY5):c.2088+1G>A	Pathogenic
2419529	NM_183357.3(ADCY5):c.2623C>T (p.Gln875Ter)	Pathogenic
2974039	NM_183357.3(ADCY5):c.415_425del (p.Ser139fs)	Pathogenic
4723342	NM_183357.3(ADCY5):c.2088+2T>C	Pathogenic
4797714	NM_183357.3(ADCY5):c.199_202dup (p.Arg68fs)	Pathogenic
4806542	NM_183357.3(ADCY5):c.324_360del (p.Asp109fs)	Pathogenic
521036	NM_183357.3(ADCY5):c.409_428del (p.Gly137fs)	Pathogenic
521978	NM_183357.3(ADCY5):c.1312dup (p.Arg438fs)	Pathogenic
524013	NM_183357.3(ADCY5):c.416_429del (p.Ser139fs)	Pathogenic
57806	GRCh38/hg38 3q13.32-21.2(chr3:119117166-125920734)x1	Pathogenic
57829	GRCh38/hg38 3q13.33-21.2(chr3:121644209-125676353)x1	Pathogenic
620201	NM_183357.3(ADCY5):c.2931C>A (p.Cys977Ter)	Pathogenic
620203	NM_183357.3(ADCY5):c.668C>A (p.Ser223Ter)	Pathogenic

SpliceAI

4830 predictions. Top by Δscore:

Variant	Effect	Δscore
3:123286680:CTCA:C	donor_loss	1.0000
3:123286681:TCAC:T	donor_loss	1.0000
3:123286682:CACCT:C	donor_loss	1.0000
3:123286683:A:AC	donor_gain	1.0000
3:123286683:AC:A	donor_gain	1.0000
3:123286683:ACC:A	donor_loss	1.0000
3:123286684:C:CT	donor_gain	1.0000
3:123286684:CC:C	donor_gain	1.0000
3:123286684:CCTGG:C	donor_gain	1.0000
3:123286806:AGCC:A	acceptor_gain	1.0000
3:123286807:GCC:G	acceptor_gain	1.0000
3:123286808:CC:C	acceptor_gain	1.0000
3:123286808:CCC:C	acceptor_gain	1.0000
3:123286809:CC:C	acceptor_gain	1.0000
3:123286810:C:CC	acceptor_gain	1.0000
3:123286810:CT:C	acceptor_loss	1.0000
3:123286811:T:A	acceptor_loss	1.0000
3:123289746:TCA:T	donor_loss	1.0000
3:123289748:A:AC	donor_gain	1.0000
3:123289749:C:CA	donor_loss	1.0000
3:123289749:C:CC	donor_gain	1.0000
3:123289749:CCG:C	donor_gain	1.0000
3:123289749:CCGA:C	donor_gain	1.0000
3:123289749:CCGAT:C	donor_gain	1.0000
3:123289795:T:TA	donor_gain	1.0000
3:123289951:TGAT:T	acceptor_gain	1.0000
3:123289952:GAT:G	acceptor_gain	1.0000
3:123289955:C:CC	acceptor_gain	1.0000
3:123289956:T:A	acceptor_loss	1.0000
3:123291114:T:TA	donor_gain	1.0000

AlphaMissense

8291 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:123284633:A:G	L1254P	1.000
3:123284666:A:T	V1243D	1.000
3:123286716:A:C	M1209R	1.000
3:123286719:C:G	R1208P	1.000
3:123286720:G:C	R1208G	1.000
3:123286720:G:T	R1208S	1.000
3:123286721:G:C	S1207R	1.000
3:123286721:G:T	S1207R	1.000
3:123286723:T:G	S1207R	1.000
3:123286725:G:T	A1206D	1.000
3:123286730:G:C	N1204K	1.000
3:123286730:G:T	N1204K	1.000
3:123286732:T:C	N1204D	1.000
3:123286732:T:G	N1204H	1.000
3:123286743:C:A	G1200V	1.000
3:123286743:C:T	G1200D	1.000
3:123286744:C:A	G1200C	1.000
3:123286744:C:G	G1200R	1.000
3:123286745:C:A	W1199C	1.000
3:123286745:C:G	W1199C	1.000
3:123286746:C:G	W1199S	1.000
3:123286747:A:G	W1199R	1.000
3:123286747:A:T	W1199R	1.000
3:123286749:A:C	I1198S	1.000
3:123286749:A:T	I1198N	1.000
3:123286751:G:C	D1197E	1.000
3:123286751:G:T	D1197E	1.000
3:123286752:T:A	D1197V	1.000
3:123286752:T:C	D1197G	1.000
3:123286752:T:G	D1197A	1.000

dbSNP variants (sampled 300 via entrez): RS1000029288 (3:123314606 G>A), RS1000052799 (3:123375163 G>A,C), RS1000055113 (3:123407465 C>T), RS1000060531 (3:123399192 G>T), RS1000062506 (3:123358785 C>T), RS1000063996 (3:123328557 C>A,T), RS1000085313 (3:123290896 T>C), RS1000137958 (3:123317883 C>T), RS1000151917 (3:123366176 C>G,T), RS1000195238 (3:123393232 T>C), RS1000195307 (3:123329021 G>A,C), RS1000202223 (3:123447129 C>A), RS1000217095 (3:123402315 G>C), RS1000228114 (3:123352298 A>G), RS1000236359 (3:123432152 A>G)

Disease associations

OMIM: gene MIM:600293 | disease phenotypes: MIM:606703, MIM:619647, MIM:619651, MIM:614065

GenCC curated gene-disease

Disease	Classification	Inheritance
dyskinesia with orofacial involvement, autosomal dominant	Strong	Autosomal dominant
neurodevelopmental disorder with hyperkinetic movements and dyskinesia	Strong	Autosomal recessive
neurodevelopmental disorder	Strong	Semidominant
familial dyskinesia and facial myokymia	Moderate	Autosomal dominant
choreatic disease	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
dyskinesia with orofacial involvement	Definitive	SD

Mondo (13): dyskinesia with orofacial involvement, autosomal dominant (MONDO:0800028), dyskinesia with orofacial involvement, autosomal recessive (MONDO:0030625), neurodevelopmental disorder with hyperkinetic movements and dyskinesia (MONDO:0859211), hereditary ataxia (MONDO:0100309), central nervous system disorder (MONDO:0002602), dyskinesia with orofacial involvement (MONDO:0031115), primary ovarian failure (MONDO:0005387), language disorder (MONDO:0004750), parkinsonian disorder (MONDO:0021095), distal myopathy with posterior leg and anterior hand involvement (MONDO:0013550), (MONDO:0011707), choreatic disease (MONDO:0001595), neurodevelopmental disorder (MONDO:0700092)

Orphanet (4): Familial dyskinesia and facial myokymia (Orphanet:324588), Hereditary ataxia (Orphanet:183518), FLNC-related handgrip and calf weakness-distal myopathy (Orphanet:63273), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000317	Facial myokymia
HP:0000467	Neck muscle weakness
HP:0000713	Agitation
HP:0000722	Compulsive behaviors
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000817	Reduced eye contact
HP:0000821	Hypothyroidism
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001270	Motor delay
HP:0001288	Gait disturbance
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001644	Dilated cardiomyopathy
HP:0002072	Chorea
HP:0002194	Delayed gross motor development
HP:0002310	Orofacial dyskinesia
HP:0002322	Resting tremor
HP:0002342	Moderate intellectual disability

GWAS associations

72 associations (top):

Study	Trait	p-value
GCST000568_9	Fasting blood glucose	7.000000e-22
GCST000569_1	Two-hour glucose challenge	7.000000e-16
GCST000648_2	Birth weight	7.000000e-15
GCST001527_26	Fasting blood glucose (BMI interaction)	4.000000e-10
GCST001527_30	Fasting blood glucose (BMI interaction)	1.000000e-07
GCST001550_5	Type 2 diabetes	6.000000e-08
GCST001758_3	Birth weight	6.000000e-20
GCST001762_37	Obesity-related traits	2.000000e-06
GCST002352_60	Type 2 diabetes	2.000000e-08
GCST002783_267	Body mass index	6.000000e-06
GCST002783_622	Body mass index	8.000000e-06
GCST003140_4	Chronic kidney disease	3.000000e-06
GCST003400_33	Type 2 diabetes	7.000000e-06
GCST004625_73	Monocyte count	2.000000e-10
GCST004627_99	Lymphocyte count	2.000000e-10
GCST004758_1	Type 2 diabetes	5.000000e-06
GCST004894_154	Type 2 diabetes	2.000000e-17
GCST004894_45	Type 2 diabetes	5.000000e-20
GCST004899_9	Gestational age at birth (maternal effect)	4.000000e-08
GCST005047_43	Type 2 diabetes	6.000000e-14
GCST005047_62	Type 2 diabetes	4.000000e-07
GCST005047_82	Type 2 diabetes	2.000000e-10
GCST005146_5	Birth weight	6.000000e-27
GCST005180_2	Homeostasis model assessment of beta-cell function	3.000000e-12
GCST005186_26	Fasting blood glucose	7.000000e-09
GCST005186_32	Fasting blood glucose	4.000000e-06
GCST005414_14	Type 2 diabetes	3.000000e-06
GCST006626_35	Pulse pressure	6.000000e-11
GCST006666_20	Lipid traits (pleiotropy) (HIPO component 1)	4.000000e-08
GCST006867_24	Type 2 diabetes	6.000000e-29

EFO canonical traits (29, from GWAS)

EFO ID	Trait name
EFO:0004307	glucose tolerance test
EFO:0004344	birth weight
EFO:0004340	body mass index
EFO:0005091	monocyte count
EFO:0004587	lymphocyte count
EFO:0005112	gestational age
EFO:0005939	parental genotype effect measurement
EFO:0004469	HOMA-B
EFO:0005763	pulse pressure measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009270	heel bone mineral density
EFO:0008328	chronotype measurement
EFO:0009924	Drugs used in diabetes use measurement
EFO:0004541	HbA1c measurement
EFO:0008336	disease progression measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004462	PR interval
EFO:0007800	body fat percentage
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007989	monocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D002493	Central Nervous System Diseases	C10.228
D002819	Chorea	C10.228.662.262.249; C10.597.350.250; C23.888.592.350.250
D007806	Language Disorders	C10.597.606.150.500; C23.888.592.604.150.500
D065886	Neurodevelopmental Disorders	F03.625
D020734	Parkinsonian Disorders	C10.228.140.079.862; C10.228.662.600
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C564676	Dyskinesia, Familial, with Facial Myokymia (supp.)
C531684	Hereditary spinal ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2097167 (PROTEIN FAMILY), CHEMBL3189 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Adenylyl cyclases (ACs)

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
NKY80	Inhibition	5.15	pIC50

ChEMBL bioactivities

53 potent at pChembl≥5 of 75 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.06	Ki	0.88	nM	CHEMBL3142312
8.77	Ki	1.7	nM	CHEMBL3142318
8.77	Ki	1.7	nM	CHEMBL3142332
8.72	Ki	1.9	nM	CHEMBL3142329
8.60	Ki	2.5	nM	CHEMBL3142331
8.59	Ki	2.6	nM	CHEMBL2369777
8.41	Ki	3.9	nM	CHEMBL2369525
8.38	Ki	4.2	nM	CHEMBL2369778
8.14	IC50	7.2	nM	CHEMBL46187
8.11	Ki	7.8	nM	CHEMBL3142313
8.10	EC50	8	nM	CHEMBL429362
7.85	Ki	14	nM	CHEMBL66087
7.77	Ki	17	nM	CHEMBL418135
7.70	Ki	20	nM	CHEMBL293907
7.54	Ki	29	nM	CHEMBL305151
7.48	Ki	33	nM	CHEMBL62123
7.16	Ki	69	nM	CHEMBL305151
7.15	EC50	71	nM	(R)-SKF-38393
7.10	EC50	80	nM	(R)-SKF-38393
6.96	Ki	110	nM	CHEMBL62412
6.85	Kd	141.2	nM	CHEMBL2115191
6.84	Ki	144	nM	CHEMBL64475
6.70	IC50	200	nM	CHEMBL432908
6.68	EC50	210	nM	CHEMBL68922
6.60	Kd	251.2	nM	CHEMBL413666
6.59	Ki	254	nM	CHEMBL62444
6.52	Ki	300	nM	CHEMBL62892
6.50	Ki	317	nM	CHEMBL64646
6.50	Kd	316.2	nM	CHEMBL2369127
6.40	IC50	400	nM	CHEMBL69185
6.22	IC50	600	nM	CHEMBL69184
6.21	Ki	610	nM	CHEMBL418468
6.20	Kd	631	nM	CHEMBL3037804
6.20	Kd	631	nM	CHEMBL328942
6.20	Kd	631	nM	CHEMBL2114177
6.20	Kd	631	nM	CHEMBL2114176
6.15	Kd	708	nM	CHEMBL328942
6.10	Kd	794.3	nM	CHEMBL328942
6.00	Ki	1000	nM	CHEMBL64955
5.85	Kd	1413	nM	CHEMBL2115192
5.58	IC50	2600	nM	CHEMBL71441
5.37	IC50	4300	nM	CHEMBL305213
5.34	IC50	4600	nM	CHEMBL302785
5.31	IC50	4900	nM	CHEMBL69750
5.28	EC50	5200	nM	CHEMBL57873
5.12	IC50	7600	nM	CHEMBL68614
5.10	IC50	7900	nM	CHEMBL302708
5.09	IC50	8200	nM	CHEMBL69809
5.03	IC50	9400	nM	CHEMBL447839

PubChem BioAssay actives

53 with measured affinity, of 218 total; 45 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
(4R,7S,10S,13S,16S)-N-[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0009	uM
(4R,7S,10S,13S,16S)-N-[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0017	uM
(4R,7S,10S,13S,16S)-N-[(2S)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0017	uM
(4R,7S,10S,13S,16S)-N-[(2R)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0019	uM
(4R,7S,10S,13S,16S)-N-[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	34312: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0025	uM
(4R,7S,10S,13S,16R)-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-N-[(2S)-5-(diaminomethylideneamino)-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-1-oxopentan-2-yl]-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0026	uM
(2S)-N-[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(4R,7S,10S,13S,16R)-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0039	uM
(4R,7S,10S,13S,16R)-N-[(2S)-6-amino-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxamide	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0042	uM
2-(1-naphthalen-1-ylsulfonylindol-6-yl)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine	34603: Antagonistic activity evaluated in adenylyl cyclase assay	ic50	0.0072	uM
(2S)-2-[[(2S)-2-[[(4R,7S,10S,13S,16S)-7-(2-amino-2-oxoethyl)-13-benzyl-20,20-dicyclopentyl-16-[(4-ethoxyphenyl)methyl]-6,9,12,15,18-pentaoxo-10-propan-2-yl-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	34311: Compound was evaluated for the inhibition constant for inhibition of 8-lysine-vasopressin stimulated adenylate cyclase of pig kidney medullary membrane	ki	0.0078	uM
(3S)-3-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-[[(2R,3S)-2-[[(2R)-2-[[(2R,3S)-2-[[2-[[(2R)-5-amino-2-[[(2R)-2-[[(2R)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(1S,2R)-1-carboxy-2-hydroxypropyl]amino]-1,4-dioxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid	34594: Ability of the Compound to activate Adenylate cyclase activity was measured by the conversion of [alpha-32P]ATP to 3'5’-cyclic AMP	ec50	0.0080	uM
3-[[4-[1-[4-(2,4-dichlorophenyl)anilino]-1-oxooctan-2-yl]oxybenzoyl]amino]propanoic acid	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.0140	uM
3-[[4-[1-[4-(1-benzofuran-2-yl)anilino]-1-oxooctan-2-yl]oxybenzoyl]amino]propanoic acid	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.0170	uM
3-[[4-[2-[[4-(1-benzofuran-2-yl)phenyl]carbamoyl]octyl]benzoyl]amino]propanoic acid	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.0200	uM
3-[[4-[3-[4-(1-benzofuran-2-yl)anilino]-2-(4-tert-butylphenyl)-3-oxopropyl]benzoyl]amino]propanoic acid	34296: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.0290	uM
3-[[4-[2-(4-tert-butylphenyl)-3-[4-(2,4-dichlorophenyl)anilino]-3-oxopropyl]benzoyl]amino]propanoic acid	34296: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.0330	uM
(5R)-5-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol	34592: Compound was tested for the adenylate cyclase stimulation	ec50	0.0710	uM
3-[[4-[2-(4-tert-butylphenyl)-3-oxo-3-[4-(trifluoromethoxy)anilino]propyl]benzoyl]amino]propanoic acid	34296: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.1100	uM
(4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoic acid	34745: pA2 value was calculated from dose-response plots generated by using different concentrations ranging between 1 and 10 uM antagonist.	kd	0.1412	uM
3-[[4-[1-(4-tert-butylphenyl)-2-oxo-2-(4-phenylanilino)ethoxy]benzoyl]amino]propanoic acid	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.1440	uM
trans-(1S,3S)-3-(6-aminopurin-9-yl)-N-hydroxycyclopentane-1-carboxamide	34755: Inhibitory activity against recombinant human adenylate cyclase 5 expressed in HEK293 cells.	ic50	0.2000	uM
(5R)-5-(4-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol	34598: Effective concentration required to stimulate Adenylate cyclase	ec50	0.2100	uM
(4R)-5-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoic acid	34745: pA2 value was calculated from dose-response plots generated by using different concentrations ranging between 1 and 10 uM antagonist.	kd	0.2512	uM
3-[[4-[[(4-tert-butylcyclohexyl)-[[4-(trifluoromethoxy)phenyl]carbamoyl]amino]methyl]benzoyl]amino]propanoic acid	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.2540	uM
3-[[4-[2-(4-tert-butylphenyl)-3-oxo-3-(4-phenylanilino)propyl]benzoyl]amino]propanoic acid	34296: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.3000	uM
(4R)-5-[[(2R)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoic acid	34745: pA2 value was calculated from dose-response plots generated by using different concentrations ranging between 1 and 10 uM antagonist.	kd	0.3162	uM
4-[1-(4-tert-butylphenyl)-2-oxo-2-(4-phenylanilino)ethoxy]-N-(2H-tetrazol-5-yl)benzamide	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.3170	uM
2-[(1S,4R)-4-(6-aminopurin-9-yl)cyclopent-2-en-1-yl]-N-hydroxyacetamide	34755: Inhibitory activity against recombinant human adenylate cyclase 5 expressed in HEK293 cells.	ic50	0.4000	uM
2-[(1R,3R)-3-(6-aminopurin-9-yl)cyclopentyl]-N-hydroxyacetamide	34755: Inhibitory activity against recombinant human adenylate cyclase 5 expressed in HEK293 cells.	ic50	0.6000	uM
3-[[4-[2-(4-tert-butylphenyl)-3-oxo-3-(quinolin-3-ylamino)propyl]benzoyl]amino]propanoic acid	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	0.6100	uM
(4S)-5-[[(2R)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoic acid	34745: pA2 value was calculated from dose-response plots generated by using different concentrations ranging between 1 and 10 uM antagonist.	kd	0.6310	uM
(4S)-5-[[(2R)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoic acid	34745: pA2 value was calculated from dose-response plots generated by using different concentrations ranging between 1 and 10 uM antagonist.	kd	0.6310	uM
(4R)-5-[[(2S,3R)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-phenylbutan-2-yl]amino]-4-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoic acid	34745: pA2 value was calculated from dose-response plots generated by using different concentrations ranging between 1 and 10 uM antagonist.	kd	0.6310	uM
(3S)-3-[[(2S)-2-[[(2S)-2-acetamido-3,3-diphenylpropanoyl]amino]-4-methylpentanoyl]amino]-4-[[(2S,3S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	34745: pA2 value was calculated from dose-response plots generated by using different concentrations ranging between 1 and 10 uM antagonist.	kd	0.6310	uM
3-[[4-[2-(4-tert-butylphenyl)-3-[4-(hydroxymethyl)anilino]-3-oxopropyl]benzoyl]amino]propanoic acid	34294: In vitro inhibitory activity against glucagon induced human adenylate cyclase	ki	1.0000	uM
(4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoic acid	34745: pA2 value was calculated from dose-response plots generated by using different concentrations ranging between 1 and 10 uM antagonist.	kd	1.4125	uM
2-[(1S,4S)-4-(6-aminopurin-9-yl)cyclopent-2-en-1-yl]-N-hydroxyacetamide	34755: Inhibitory activity against recombinant human adenylate cyclase 5 expressed in HEK293 cells.	ic50	2.6000	uM
2-[(1R,4S)-4-(6-aminopurin-9-yl)cyclopent-2-en-1-yl]-N-hydroxyacetamide	34755: Inhibitory activity against recombinant human adenylate cyclase 5 expressed in HEK293 cells.	ic50	4.3000	uM
cis-(1R,3S)-3-(6-aminopurin-9-yl)-N-hydroxycyclopentane-1-carboxamide	34755: Inhibitory activity against recombinant human adenylate cyclase 5 expressed in HEK293 cells.	ic50	4.6000	uM
(1R,4R)-4-(6-aminopurin-9-yl)-N-hydroxycyclopent-2-ene-1-carboxamide	34755: Inhibitory activity against recombinant human adenylate cyclase 5 expressed in HEK293 cells.	ic50	4.9000	uM
2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol	34592: Compound was tested for the adenylate cyclase stimulation	ec50	5.2000	uM
5-(6-aminopurin-9-yl)-N-hydroxypentanamide	215937: Inhibitory concentration against type V Adenyl Cyclase enzyme	ic50	7.6000	uM
4-(6-aminopurin-9-yl)-N-hydroxybutanamide	215937: Inhibitory concentration against type V Adenyl Cyclase enzyme	ic50	7.9000	uM
2-[(1S,4R)-4-(6-aminopurin-9-yl)cyclopent-2-en-1-yl]acetic acid	34755: Inhibitory activity against recombinant human adenylate cyclase 5 expressed in HEK293 cells.	ic50	8.2000	uM
2-[(1S,3S)-3-(6-aminopurin-9-yl)cyclopentyl]-N-hydroxyacetamide	34755: Inhibitory activity against recombinant human adenylate cyclase 5 expressed in HEK293 cells.	ic50	9.4000	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
sodium arsenite	decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1
abrine	decreases expression	1
perfluorobutanesulfonic acid	affects expression, affects cotreatment	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Bleomycin	increases expression	1
Calcium	decreases activity	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	increases expression	1
Magnesium	increases activity	1
Methapyrilene	increases methylation	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases methylation	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

43 unique, capped per target: 33 binding, 9 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3284336	Binding	Agonist activity at adenylyl cyclase (unknown origin) at 1.35 x 10’-4 M	Synthesis of a fragment of human parathyroid hormore, hPTH-(44-68). — J Med Chem
CHEMBL645298	Functional	In vitro antagonist activity was measured by inhibition of vasopressin-stimulated adenylate cyclase in renal medullary preparation in pig	Dicarbavasopressin antagonist analogues exhibit reduced in vivo agonist activity. — J Med Chem
CHEMBL4685441	ADMET	Agonist activity at recombinant human AC5 expressed in HEK293 cells assessed as increase in cAMP level at 50 uM measured after 30 mins by LANCE Ultra cAMP Detection kit method	The discovery, design and synthesis of potent agonists of adenylyl cyclase type 2 by virtual screening combining biological evaluation. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_E6MB	UCLi026-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT01340950	PHASE4	COMPLETED	Clinical Trial of Brain-Penetrating HIV Drugs to Prevent Cognitive Impairment in China
NCT01445639	PHASE4	COMPLETED	Dexmedetomidine in Patients After Intracranial Surgery
NCT01662414	PHASE4	COMPLETED	Effect of Undenatured Cysteine-Rich Whey Protein Isolate (HMS 90®) in Patients With Parkinson’s Disease
NCT04399343	PHASE4	UNKNOWN	Dexmedetomidine for Prevention of Postoperative Delirium After Intracranial Operation for Brain Tumor
NCT04494828	PHASE4	COMPLETED	Impact Dexmedetomidine on Postoperative Delirium in Patients After Intracranial Operation for Brain Tumor
NCT04871464	PHASE4	UNKNOWN	Role and Mechanism of Probiotics in Improving Motor Symptoms in Mild to Moderate Parkinson’s Disease
NCT04898270	PHASE4	COMPLETED	Adjunctive Use of Fute (Flupentixol) in Multi-acting Receptor-targeted Antipsychotics Treated Schizophrenia Patients
NCT05068349	PHASE4	UNKNOWN	For Patients With Ischemic Stroke, Clinically Study the Effectiveness and Safety of Butylphthalide.
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00323310	PHASE3	TERMINATED	Safety and Efficacy of MultiHance in Pediatric Patients
NCT00395460	PHASE3	COMPLETED	Efficacy and Safety Study to Evaluate Gadavist (Gadobutrol) as Contrast Agent in Magnetic Resonance Imaging (MRI) of Brain or Spine Diseases in Chinese Patients
NCT00623467	PHASE3	COMPLETED	Safety and Efficacy of Gadobutrol 1.0 Molar ( Gadavist ) in Patients for Central Nervous System (CNS) Imaging
NCT00709852	PHASE3	COMPLETED	Safety and Efficacy of Gadobutrol 1.0 Molar (Gadavist) in Patients for Central Nervous System (CNS) Imaging
NCT01211873	PHASE3	COMPLETED	Safety and Efficacy Evaluation of DOTAREM® in MRI of Central Nervous System (CNS) Lesions
NCT04639310	PHASE3	TERMINATED	XEN496 (Ezogabine) in Children With KCNQ2 Developmental and Epileptic Encephalopathy
NCT04912856	PHASE3	TERMINATED	An Open-Label Extension of the Study XEN496 (Ezogabine) in Children With KCNQ2-DEE
NCT05508789	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Donanemab (LY3002813) in Participants With Early Symptomatic Alzheimer’s Disease (TRAILBLAZER-ALZ 5)
NCT05738486	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Different Donanemab (LY3002813) Dosing Regimens in Adults With Early Alzheimer’s Disease (TRAILBLAZER-ALZ 6)
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00033150	PHASE3	COMPLETED	A Comparison of Language Intervention Programs
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00406029	PHASE2	COMPLETED	Dyskinesia in Parkinson’s Disease (Study P04501)
NCT00537017	PHASE2	COMPLETED	Follow Up Safety Study of SCH 420814 in Subjects With Parkinson’s Disease (P05175)
NCT00968851	PHASE2	COMPLETED	Safety and Cognitive Function Study of EVP-6124 in Patients With Schizophrenia
NCT01073228	PHASE2	COMPLETED	Safety and Cognitive Function Study of EVP-6124 in Patients With Mild to Moderate Alzheimer’s Disease
NCT02248701	PHASE2	TERMINATED	Testosterone Plus Finasteride Treatment After Spinal Cord Injury