GUCY1B1
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Also known as GC-SB3GC-S-beta-1
Summary
GUCY1B1 (guanylate cyclase 1 soluble subunit beta 1, HGNC:4687) is a protein-coding gene on chromosome 4q32.1, encoding Guanylate cyclase soluble subunit beta-1 (Q02153). Mediates responses to nitric oxide (NO) by catalyzing the biosynthesis of the signaling molecule cGMP.
This gene encodes the beta subunit of the soluble guanylate cyclase (sGC), which catalyzes the conversion of GTP (guanosine triphosphate) to cGMP (cyclic guanosine monophosphate). The encoded protein contains an HNOX domain, which serves as a receptor for ligands such as nitric oxide, oxygen and nitrovasodilator drugs. Alternative splicing results in multiple transcript variants.
Source: NCBI Gene 2983 — RefSeq curated summary.
At a glance
- GWAS associations: 10
- Clinical variants (ClinVar): 55 total
- Druggable target: yes — 2 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_000857
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:4687 |
| Approved symbol | GUCY1B1 |
| Name | guanylate cyclase 1 soluble subunit beta 1 |
| Location | 4q32.1 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | GC-SB3, GC-S-beta-1 |
| Ensembl gene | ENSG00000061918 |
| Ensembl biotype | protein_coding |
| OMIM | 139397 |
| Entrez | 2983 |
Gene structure
Transcript identifiers
Ensembl transcripts: 18 — 18 protein_coding
ENST00000264424, ENST00000502959, ENST00000503520, ENST00000505154, ENST00000505764, ENST00000507146, ENST00000513437, ENST00000652626, ENST00000879916, ENST00000879917, ENST00000879918, ENST00000879919, ENST00000879920, ENST00000936140, ENST00000971852, ENST00000971853, ENST00000971854, ENST00000971855
RefSeq mRNA: 6 — MANE Select: NM_000857
NM_000857, NM_001291951, NM_001291952, NM_001291953, NM_001291954, NM_001291955
CCDS: CCDS47154, CCDS75203, CCDS77975, CCDS77976, CCDS77977, CCDS77978
Canonical transcript exons
ENST00000264424 — 14 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000385694 | 155789714 | 155789911 |
| ENSE00000740142 | 155805103 | 155805229 |
| ENSE00000740145 | 155804593 | 155804747 |
| ENSE00000740150 | 155802342 | 155802579 |
| ENSE00000740152 | 155799877 | 155800074 |
| ENSE00000740154 | 155796377 | 155796510 |
| ENSE00000740156 | 155795341 | 155795457 |
| ENSE00000740158 | 155793856 | 155794086 |
| ENSE00000856058 | 155803624 | 155803764 |
| ENSE00001716583 | 155806386 | 155807811 |
| ENSE00002034801 | 155759021 | 155759143 |
| ENSE00003534048 | 155759787 | 155759860 |
| ENSE00003624850 | 155777524 | 155777642 |
| ENSE00003662474 | 155774968 | 155775068 |
Expression profiles
Bgee: expression breadth ubiquitous, 284 present calls, max score 98.32.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.4432 / max 574.1446, expressed in 1185 samples.
FANTOM5 promoters (3 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 50215 | 14.0439 | 1175 |
| 50214 | 0.3300 | 125 |
| 50216 | 0.0694 | 41 |
Top tissues by expression
294 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| middle temporal gyrus | UBERON:0002771 | 98.32 | gold quality |
| orbitofrontal cortex | UBERON:0004167 | 97.84 | gold quality |
| lateral nuclear group of thalamus | UBERON:0002736 | 97.44 | gold quality |
| superior frontal gyrus | UBERON:0002661 | 97.43 | gold quality |
| Brodmann (1909) area 46 | UBERON:0006483 | 97.33 | gold quality |
| postcentral gyrus | UBERON:0002581 | 96.97 | gold quality |
| Brodmann (1909) area 23 | UBERON:0013554 | 96.90 | gold quality |
| parietal lobe | UBERON:0001872 | 96.85 | gold quality |
| substantia nigra pars compacta | UBERON:0001965 | 96.82 | gold quality |
| pons | UBERON:0000988 | 96.75 | gold quality |
| entorhinal cortex | UBERON:0002728 | 96.64 | gold quality |
| superior vestibular nucleus | UBERON:0007227 | 96.36 | gold quality |
| lateral globus pallidus | UBERON:0002476 | 96.10 | gold quality |
| substantia nigra pars reticulata | UBERON:0001966 | 95.67 | gold quality |
| CA1 field of hippocampus | UBERON:0003881 | 95.52 | gold quality |
| blood vessel layer | UBERON:0004797 | 95.51 | gold quality |
| prefrontal cortex | UBERON:0000451 | 95.33 | gold quality |
| heart right ventricle | UBERON:0002080 | 95.05 | gold quality |
| ventral tegmental area | UBERON:0002691 | 94.87 | gold quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 94.86 | gold quality |
| type B pancreatic cell | CL:0000169 | 94.85 | gold quality |
| Brodmann (1909) area 10 | UBERON:0013541 | 94.59 | gold quality |
| urethra | UBERON:0000057 | 94.48 | gold quality |
| frontal cortex | UBERON:0001870 | 94.36 | gold quality |
| endothelial cell | CL:0000115 | 94.32 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 94.31 | gold quality |
| nucleus accumbens | UBERON:0001882 | 94.17 | gold quality |
| cerebral cortex | UBERON:0000956 | 93.77 | gold quality |
| neocortex | UBERON:0001950 | 93.71 | gold quality |
| visceral pleura | UBERON:0002401 | 93.65 | gold quality |
Single-cell (SCXA)
Detected in 5 experiment(s), a significant marker in 5.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-CURD-112 | yes | 38.11 |
| E-HCAD-11 | yes | 21.51 |
| E-MTAB-8410 | yes | 16.06 |
| E-ANND-3 | yes | 13.12 |
| E-MTAB-9067 | yes | 12.43 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): GFI1, NFIC
miRNA regulators (miRDB)
113 targeting GUCY1B1, 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-5692A | 100.00 | 74.40 | 6850 |
| HSA-MIR-340-5P | 100.00 | 72.50 | 4437 |
| HSA-LET-7A-3P | 100.00 | 74.03 | 3932 |
| HSA-LET-7B-3P | 100.00 | 74.08 | 3913 |
| HSA-LET-7F-1-3P | 100.00 | 74.02 | 3928 |
| HSA-MIR-98-3P | 100.00 | 74.08 | 3907 |
| HSA-MIR-4776-3P | 100.00 | 68.73 | 1340 |
| HSA-MIR-4789-5P | 99.98 | 70.76 | 2721 |
| HSA-MIR-548N | 99.98 | 71.94 | 4170 |
| HSA-MIR-12136 | 99.98 | 72.81 | 5713 |
| HSA-LET-7F-2-3P | 99.98 | 70.98 | 2588 |
| HSA-MIR-1185-1-3P | 99.98 | 71.04 | 2593 |
| HSA-MIR-1185-2-3P | 99.98 | 71.04 | 2593 |
| HSA-MIR-5696 | 99.98 | 72.36 | 4487 |
| HSA-MIR-3065-5P | 99.97 | 71.56 | 3281 |
| HSA-MIR-548AN | 99.97 | 70.91 | 2817 |
| HSA-MIR-3658 | 99.96 | 73.87 | 4379 |
| HSA-MIR-548AJ-3P | 99.96 | 73.38 | 5345 |
| HSA-MIR-548X-3P | 99.96 | 73.38 | 5345 |
| HSA-MIR-548AB | 99.95 | 71.31 | 3488 |
| HSA-MIR-559 | 99.95 | 72.28 | 3609 |
| HSA-MIR-548A-5P | 99.94 | 71.27 | 3482 |
| HSA-MIR-548AD-5P | 99.94 | 71.23 | 3502 |
| HSA-MIR-548AE-5P | 99.94 | 71.23 | 3502 |
| HSA-MIR-548AK | 99.94 | 71.24 | 3488 |
| HSA-MIR-548AM-5P | 99.94 | 71.24 | 3488 |
| HSA-MIR-548AR-5P | 99.94 | 71.28 | 3515 |
| HSA-MIR-548AU-5P | 99.94 | 71.24 | 3488 |
| HSA-MIR-548AY-5P | 99.94 | 71.23 | 3502 |
| HSA-MIR-548B-5P | 99.94 | 71.23 | 3502 |
Literature-anchored findings (GeneRIF, showing 16)
- Although soluble guanylate cyclase(sGC) beta1-subunit expression was increased in mononuclear cells from patients with erectile dysfunction, the sGC activity was reduced (PMID:16528291)
- Results show that NOGCbeta1 and GC-A interact and that NOGCbeta1 regulates atrial natriuretic peptide signaling in HK-2 cells. (PMID:20024606)
- recombinant soluble guanylate cyclase (sGC) beta1 subunit and truncated N-terminal fragments expressed in E. coli; studied interaction between NO and sGC and schematic mechanism was proposed; study provides insights into structure and NO-binding of sGC (PMID:20063108)
- The mutant analysis indicated an importance for not only certain dimerization residue positions, but also an important role for other faces of the coiled coil dimer which might perhaps interact with adjacent domains (PMID:20105301)
- Data show that show that it is possible to directly monitor the sGC haem oxidation state in intact cells. By inserting the TC motif into the coding sequence of the beta1 subunit of sGC in transiently transfected Chinese hamster ovary cells. (PMID:21858179)
- We concluded that the alpha-subunit and the beta(1)(191-619) domain exert structural strains on the heme domain. (PMID:22223482)
- The results indicate that in comparison with the alpha-1 beta-1 isoform, the brain alpha-2 beta-1 isoform exhibits a distinctly different CO/NO affinity and binding rate in favor of NO signaling. (PMID:22426988)
- The G-protein regulator LGN modulates the activity of the NO receptor soluble guanylate cyclase (PMID:22690686)
- Gene expression in dendritic cells of CCL5 and CXCL5 as well as TIMP1 and GUCY1B3 showed a significant increase within the first 4 days after trauma. (PMID:23179318)
- Dynamic interplay between hsp90, apo-sGC-beta1, and sGC-alpha1 in response to NO is unprecedented and represent new steps by which cells can modulate the heme content and activity of sGC for signaling cascades. (PMID:24733395)
- The kinetics of heme loss from oxidized sGC was monitored by a new method based on the heme group de-quenching the fluorescence of FlAsH-EDT2. (PMID:26876536)
- Inhibition of HDAC3 with targeted therapy could benefit treatment of the diseases associated with sGCbeta1 down-regulation and/or deficiency such as cancer and several vascular-related diseases. (PMID:27279362)
- Human Red Blood Cells carry catalytically active alpha1beta1-soluble guanylate cyclase (isoform 1). Red cell soluble guanylate cyclase activity is fully preserved in patients with stable coronary artery disease. (PMID:29024896)
- Our observations revealed that rs7638A/C polymorphism of GUCY1B3 and the longer telomere length inclined toward adaptation to high altitude. (PMID:29443612)
- Results suggest mechanistic insights into the molecular pathway for soluble guanylyl cyclase (sGC) activation. (PMID:31645439)
- Inflammation in the Human Periodontium Induces Downregulation of the alpha1- and beta1-Subunits of the sGC in Cementoclasts. (PMID:33430449)
Cross-species orthologs
4 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | gucy1b1 | ENSDARG00000086790 |
| mus_musculus | Gucy1b1 | ENSMUSG00000028005 |
| rattus_norvegicus | Gucy1b1 | ENSRNOG00000012060 |
| drosophila_melanogaster | Gycbeta100B | FBGN0013973 |
Paralogs (17): 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), ADCY5 (ENSG00000173175), ADCY6 (ENSG00000174233)
Protein
Protein identifiers
Guanylate cyclase soluble subunit beta-1 — Q02153 (reviewed: Q02153)
Alternative names: Guanylate cyclase soluble subunit beta-3, Soluble guanylate cyclase small subunit
All UniProt accessions (5): Q02153, A0A494C1B9, B7Z685, D6RC99, E9PCN2
UniProt curated annotations — full annotation on UniProt →
Function. Mediates responses to nitric oxide (NO) by catalyzing the biosynthesis of the signaling molecule cGMP.
Subunit / interactions. The active enzyme is formed by a heterodimer of an alpha and a beta subunit. Heterodimer with GUCY1A1. Can also form inactive homodimers in vitro.
Subcellular location. Cytoplasm.
Tissue specificity. Detected in brain cortex and cerebellum (at protein level).
Activity regulation. Activated by nitric oxide in the presence of magnesium or manganese ions.
Cofactor. Binds 1 or 2 heme groups per heterodimer. Heme is required for responding to nitric oxide, but not for catalytic activity.
Miscellaneous. There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms.
Similarity. Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.
Isoforms (3)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q02153-1 | HSGC-1 | yes |
| Q02153-2 | HSGC-2 | |
| Q02153-3 | 3 |
RefSeq proteins (6): NP_000848, NP_001278880, NP_001278881, NP_001278882, NP_001278883, NP_001278884 (=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR001054 | A/G_cyclase | Domain |
| IPR011644 | Heme_NO-bd | Domain |
| IPR011645 | HNOB_dom_associated | Domain |
| IPR018297 | A/G_cyclase_CS | Conserved_site |
| IPR024096 | NO_sig/Golgi_transp_ligand-bd | Homologous_superfamily |
| IPR029787 | Nucleotide_cyclase | Homologous_superfamily |
| IPR038158 | H-NOX_domain_sf | Homologous_superfamily |
| IPR042463 | HNOB_dom_associated_sf | Homologous_superfamily |
Pfam: PF00211, PF07700, PF07701
Enzyme classification (BRENDA):
- EC 4.6.1.2 — guanylate cyclase (BRENDA: 58 organisms, 213 substrates, 212 inhibitors, 100 Km, 16 kcat entries)
Substrate kinetics (BRENDA)
5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| GTP | 0.01–6.09 | 90 |
| 2’-O-(N-METHYLANTHRANILOYL) GUANOSINE 5’-TRIPHOS | 0.0357 | 1 |
| GUANYL-(BETA,GAMMA-METHYLENE)-DIPHOSPHONATE | 0.37 | 1 |
| GUANYL-IMIDODIPHOSPHATE | 0.07 | 1 |
| MN2+ | 2.7 | 1 |
Catalyzed reactions (Rhea), 1 shown:
- GTP = 3’,5’-cyclic GMP + diphosphate (RHEA:13665)
UniProt features (60 total): strand 25, helix 22, turn 8, splice variant 2, chain 1, domain 1, binding site 1
Structure
Experimental structures (PDB)
14 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 2WZ1 | X-RAY DIFFRACTION | 1.63 |
| 4NI2 | X-RAY DIFFRACTION | 1.9 |
| 3UVJ | X-RAY DIFFRACTION | 2.08 |
| 8HBF | ELECTRON MICROSCOPY | 3.1 |
| 8HBH | ELECTRON MICROSCOPY | 3.1 |
| 8HBE | ELECTRON MICROSCOPY | 3.2 |
| 7D9R | ELECTRON MICROSCOPY | 3.7 |
| 6JT2 | ELECTRON MICROSCOPY | 3.8 |
| 7D9U | ELECTRON MICROSCOPY | 3.8 |
| 6JT1 | ELECTRON MICROSCOPY | 3.9 |
| 7D9S | ELECTRON MICROSCOPY | 3.9 |
| 6JT0 | ELECTRON MICROSCOPY | 4 |
| 7D9T | ELECTRON MICROSCOPY | 4.1 |
| 5MNW | SOLUTION NMR |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q02153-F1 | 85.39 | 0.42 |
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 (1): 105 (proximal binding residue)
Function
Pathways and Gene Ontology
Reactome pathways
2 pathways
| ID | Pathway |
|---|---|
| R-HSA-392154 | Nitric oxide stimulates guanylate cyclase |
| R-HSA-445355 | Smooth Muscle Contraction |
MSigDB gene sets: 251 (showing top):
GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, chr4q32, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CGMP_BIOSYNTHETIC_PROCESS, GOZGIT_ESR1_TARGETS_DN, MODULE_445, MODULE_65, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CYCLIC_NUCLEOTIDE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS
GO Biological Process (9): cGMP biosynthetic process (GO:0006182), obsolete nitric oxide mediated signal transduction (GO:0007263), blood circulation (GO:0008015), obsolete cGMP-mediated signaling (GO:0019934), nitric oxide-cGMP-mediated signaling (GO:0038060), response to oxygen levels (GO:0070482), cellular response to nitric oxide (GO:0071732), cyclic nucleotide biosynthetic process (GO:0009190), intracellular signal transduction (GO:0035556)
GO Molecular Function (14): adenylate cyclase activity (GO:0004016), guanylate cyclase activity (GO:0004383), GTP binding (GO:0005525), heme binding (GO:0020037), signaling receptor activity (GO:0038023), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872), cytidylate cyclase activity (GO:0047805), Hsp90 protein binding (GO:0051879), nitric oxide binding (GO:0070026), nucleotide binding (GO:0000166), protein binding (GO:0005515), lyase activity (GO:0016829), phosphorus-oxygen lyase activity (GO:0016849)
GO Cellular Component (6): cytosol (GO:0005829), guanylate cyclase complex, soluble (GO:0008074), presynaptic active zone cytoplasmic component (GO:0098831), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), protein-containing complex (GO:0032991)
Reactome top-level categories
Rollup of top-2 pathways:
| Category | Pathways |
|---|---|
| Platelet homeostasis | 1 |
| Muscle contraction | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cyclase activity | 3 |
| phosphorus-oxygen lyase activity | 3 |
| cyclic nucleotide biosynthetic process | 2 |
| intracellular anatomical structure | 2 |
| binding | 2 |
| cellular anatomical structure | 2 |
| purine ribonucleotide biosynthetic process | 1 |
| cGMP metabolic process | 1 |
| circulatory system process | 1 |
| intracellular signaling cassette | 1 |
| response to abiotic stimulus | 1 |
| response to nitric oxide | 1 |
| cellular response to oxygen-containing compound | 1 |
| cellular response to reactive nitrogen species | 1 |
| nucleotide biosynthetic process | 1 |
| cyclic nucleotide metabolic process | 1 |
| signal transduction | 1 |
| cGMP biosynthetic process | 1 |
| guanyl ribonucleotide binding | 1 |
| purine ribonucleoside triphosphate binding | 1 |
| tetrapyrrole binding | 1 |
| molecular transducer activity | 1 |
| cation binding | 1 |
| heat shock protein binding | 1 |
| small molecule binding | 1 |
| nucleoside phosphate binding | 1 |
| heterocyclic compound binding | 1 |
| catalytic activity | 1 |
| lyase activity | 1 |
| cytoplasm | 1 |
| cytosol | 1 |
| catalytic complex | 1 |
| presynaptic active zone | 1 |
| cell cortex region | 1 |
| synapse | 1 |
| cellular_component | 1 |
Protein interactions and networks
STRING
1138 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| GUCY1B1 | GUCY1A1 | Q02108 | 950 |
| GUCY1B1 | GUCY1A2 | P33402 | 834 |
| GUCY1B1 | PDE5A | O76074 | 561 |
| GUCY1B1 | AK8 | Q96MA6 | 488 |
| GUCY1B1 | PDE7B | Q9NP56 | 486 |
| GUCY1B1 | PRKG2 | Q13237 | 451 |
| GUCY1B1 | NTPCR | Q9BSD7 | 451 |
| GUCY1B1 | PRKG1 | P14619 | 444 |
| GUCY1B1 | LY6G6F | Q5SQ64 | 441 |
| GUCY1B1 | DLG4 | P78352 | 424 |
| GUCY1B1 | CTSO | P43234 | 407 |
| GUCY1B1 | ATIC | P31939 | 403 |
| GUCY1B1 | CANT1 | Q8WVQ1 | 395 |
| GUCY1B1 | IRAG1 | Q9Y6F6 | 390 |
| GUCY1B1 | GFI1B | Q5VTD9 | 385 |
IntAct
25 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| LIN7A | CASK | psi-mi:“MI:0914”(association) | 0.830 |
| GUCY1A1 | GUCY1B1 | psi-mi:“MI:0407”(direct interaction) | 0.670 |
| GUCY1A1 | GUCY1B1 | psi-mi:“MI:0883”(gtpase reaction) | 0.670 |
| GUCY1B1 | GUCY1B1 | psi-mi:“MI:0407”(direct interaction) | 0.440 |
| IMMP2L | ANKHD1-EIF4EBP3 | psi-mi:“MI:0914”(association) | 0.350 |
| ABCD4 | psi-mi:“MI:0914”(association) | 0.350 | |
| OR1M1 | NBAS | psi-mi:“MI:0914”(association) | 0.350 |
| ZDHHC12 | NBAS | psi-mi:“MI:0914”(association) | 0.350 |
| PRKY | METTL15 | psi-mi:“MI:0914”(association) | 0.350 |
| OR6T1 | PSMD11 | psi-mi:“MI:0914”(association) | 0.350 |
| HNRNPCL2 | SMCHD1 | psi-mi:“MI:0914”(association) | 0.350 |
| TLR9 | ABCD4 | psi-mi:“MI:0914”(association) | 0.350 |
| ABCA2 | ABCD4 | psi-mi:“MI:0914”(association) | 0.350 |
| GRIN3B | DAPK3 | psi-mi:“MI:0914”(association) | 0.350 |
| ANKMY2 | ADCY6 | psi-mi:“MI:0914”(association) | 0.350 |
| OR2M7 | MARCHF6 | psi-mi:“MI:0914”(association) | 0.350 |
| SLC12A3 | SNX2 | psi-mi:“MI:0914”(association) | 0.350 |
| GUCY1B1 | MYCBP2 | psi-mi:“MI:0914”(association) | 0.350 |
| USP28 | OFD1 | psi-mi:“MI:0914”(association) | 0.350 |
| NOX5 | RNASEH2A | psi-mi:“MI:0914”(association) | 0.350 |
| CHRNA7 | UFL1 | psi-mi:“MI:0914”(association) | 0.350 |
| GUCY1B1 | MXRA7 | psi-mi:“MI:0914”(association) | 0.350 |
| SLC27A6 | NBAS | psi-mi:“MI:0914”(association) | 0.350 |
| DSCR9 | GUCY1B1 | psi-mi:“MI:0915”(physical association) | 0.000 |
BioGRID (56): GUCY1B3 (Affinity Capture-MS), GUCY1A2 (Affinity Capture-MS), GUCY1A3 (Affinity Capture-MS), MXRA7 (Affinity Capture-MS), GUCY1B3 (Affinity Capture-MS), UACA (Affinity Capture-MS), GUCY1B3 (Affinity Capture-MS), MTFR2 (Affinity Capture-MS), MYCBP2 (Affinity Capture-MS), BBS2 (Affinity Capture-MS), MUL1 (Affinity Capture-MS), GUCY1B3 (Affinity Capture-RNA), NOS3 (Reconstituted Complex), HSP90AA1 (Reconstituted Complex), NOS3 (Affinity Capture-Western)
ESM2 similar proteins: A0A2R8QFQ6, A0A2R8RWN9, D3Z7P3, E9PV86, G3MWR8, O54865, O60907, O89050, O94925, P13264, P16068, P20595, P58058, Q02153, Q08211, Q12800, Q13042, Q14722, Q28141, Q28D01, Q3MHJ2, Q3ULA2, Q4R8H1, Q4ZHR9, Q5R874, Q5RB35, Q5SP67, Q5SRY7, Q5ZHN3, Q6DN14, Q7RTP6, Q7T2U9, Q7Z6J6, Q8BTG7, Q8C6G8, Q8CJ19, Q8K4Q0, Q8N122, Q8N2K0, Q8R349
Diamond homologs: A0A078BQP2, A0A0U1RPR8, E7EAU8, H2L002, O02298, O02740, O16715, O19179, O54865, O62179, O75343, P0A4Y1, P16065, P16066, P16068, P18293, P18910, P19686, P19687, P20594, P20595, P22717, P23897, P25092, P26770, P33402, P51840, P51841, P51842, P52785, P55202, P55203, P55204, P70106, P90895, P91550, P92006, P9WQ34, P9WQ35, Q02108
SIGNOR signaling
2 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| GUCY1B1 | “form complex” | GUCY1A2-B3 | binding |
| GUCY1B1 | “form complex” | GUCY1A3-B3 | binding |
Disease & clinical
Clinical variants and AI predictions
ClinVar
55 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 43 |
| Likely benign | 0 |
| Benign | 0 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
2338 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 4:155759782:CGCAG:C | acceptor_loss | 1.0000 |
| 4:155759785:A:AG | acceptor_gain | 1.0000 |
| 4:155759785:AGTAC:A | acceptor_gain | 1.0000 |
| 4:155759786:G:GA | acceptor_gain | 1.0000 |
| 4:155759786:GT:G | acceptor_gain | 1.0000 |
| 4:155759786:GTAC:G | acceptor_gain | 1.0000 |
| 4:155759786:GTACG:G | acceptor_gain | 1.0000 |
| 4:155759861:G:GG | donor_gain | 1.0000 |
| 4:155774952:T:TA | acceptor_gain | 1.0000 |
| 4:155774958:T:TA | acceptor_gain | 1.0000 |
| 4:155774964:CCAG:C | acceptor_loss | 1.0000 |
| 4:155774966:A:AG | acceptor_gain | 1.0000 |
| 4:155774966:AG:A | acceptor_loss | 1.0000 |
| 4:155774967:G:GA | acceptor_gain | 1.0000 |
| 4:155774967:GA:G | acceptor_gain | 1.0000 |
| 4:155774967:GAA:G | acceptor_gain | 1.0000 |
| 4:155774967:GAAA:G | acceptor_gain | 1.0000 |
| 4:155774967:GAAAA:G | acceptor_gain | 1.0000 |
| 4:155775064:CCTCA:C | donor_gain | 1.0000 |
| 4:155775065:CTCAG:C | donor_loss | 1.0000 |
| 4:155775066:TCA:T | donor_gain | 1.0000 |
| 4:155775067:CA:C | donor_gain | 1.0000 |
| 4:155775067:CAGT:C | donor_loss | 1.0000 |
| 4:155775068:AGTA:A | donor_loss | 1.0000 |
| 4:155775069:G:GG | donor_gain | 1.0000 |
| 4:155775070:TAAG:T | donor_loss | 1.0000 |
| 4:155775071:AAGTT:A | donor_loss | 1.0000 |
| 4:155777508:T:A | acceptor_gain | 1.0000 |
| 4:155777511:A:AG | acceptor_gain | 1.0000 |
| 4:155777517:A:AG | acceptor_gain | 1.0000 |
AlphaMissense
4101 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 4:155759790:G:A | G3R | 1.000 |
| 4:155759790:G:C | G3R | 1.000 |
| 4:155759791:G:A | G3E | 1.000 |
| 4:155775053:G:C | A55P | 1.000 |
| 4:155777556:G:A | G71R | 1.000 |
| 4:155777556:G:C | G71R | 1.000 |
| 4:155777556:G:T | G71W | 1.000 |
| 4:155777557:G:A | G71E | 1.000 |
| 4:155777557:G:T | G71V | 1.000 |
| 4:155777578:G:A | C78Y | 1.000 |
| 4:155777579:C:G | C78W | 1.000 |
| 4:155777605:T:C | L87S | 1.000 |
| 4:155777614:T:C | L90P | 1.000 |
| 4:155777616:G:C | G91R | 1.000 |
| 4:155777616:G:T | G91C | 1.000 |
| 4:155777617:G:A | G91D | 1.000 |
| 4:155777617:G:T | G91V | 1.000 |
| 4:155777634:T:C | F97L | 1.000 |
| 4:155777635:T:C | F97S | 1.000 |
| 4:155777636:T:A | F97L | 1.000 |
| 4:155777636:T:G | F97L | 1.000 |
| 4:155777638:T:C | L98P | 1.000 |
| 4:155789718:T:A | L101H | 1.000 |
| 4:155789718:T:C | L101P | 1.000 |
| 4:155789720:G:C | D102H | 1.000 |
| 4:155789720:G:T | D102Y | 1.000 |
| 4:155789721:A:C | D102A | 1.000 |
| 4:155789721:A:T | D102V | 1.000 |
| 4:155789727:T:C | L104P | 1.000 |
| 4:155789729:C:G | H105D | 1.000 |
dbSNP variants (sampled 300 via entrez): RS1000028198 (4:155767712 C>T), RS1000181745 (4:155789242 A>C), RS1000214956 (4:155795901 A>G), RS1000241336 (4:155788301 A>G), RS10003470 (4:155788060 A>G), RS1000401243 (4:155780938 A>C,G), RS1000495696 (4:155771386 T>C,G), RS1000728651 (4:155804542 A>G,T), RS1000739942 (4:155804345 C>T), RS1000784620 (4:155778053 A>G), RS1000801418 (4:155786931 A>G), RS1000842573 (4:155788732 G>A), RS1000873490 (4:155760869 C>G), RS1000886782 (4:155757800 T>C), RS1000913272 (4:155807557 T>C)
Disease associations
OMIM: gene MIM:139397 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
10 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST001227_20 | Systolic blood pressure | 1.000000e-06 |
| GCST001228_9 | Diastolic blood pressure | 2.000000e-10 |
| GCST001236_17 | Blood pressure | 3.000000e-07 |
| GCST004278_64 | Pulse pressure | 7.000000e-14 |
| GCST004776_19 | Systolic blood pressure | 5.000000e-06 |
| GCST004777_5 | Diastolic blood pressure | 2.000000e-06 |
| GCST006259_49 | Systolic blood pressure | 7.000000e-09 |
| GCST007707_36 | Hypertension | 6.000000e-06 |
| GCST009840_2 | Diabetic retinopathy in type 2 diabetes | 4.000000e-06 |
| GCST010867_31 | Coronary artery disease | 3.000000e-08 |
EFO canonical traits (4, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0006335 | systolic blood pressure |
| EFO:0006336 | diastolic blood pressure |
| EFO:0006340 | mean arterial pressure |
| EFO:0005763 | pulse pressure measurement |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (2): CHEMBL2111348 (PROTEIN COMPLEX GROUP), CHEMBL3137281 (PROTEIN COMPLEX)
Molecules with ChEMBL bioactivity
2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 8,203 (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 |
|---|---|---|---|
| CHEMBL12610 | BENZYDAMINE | 4 | 8,193 |
| CHEMBL5944803 | FRESPACIGUAT | 2 | 10 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: catalytic receptor — Nitric oxide (NO)-sensitive (soluble) guanylyl cyclase
Binding affinities (BindingDB)
465 measured of 465 human assays (465 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| 4-amino-2-[6-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-5-[3-(2H-tetrazol-5-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-6-one | KI | 0.068 nM | US-10428076: Soluble guanylate cyclase stimulators |
| 3-[2-[4-[(5S)-2-[6-chloro-1-[(2-fluorophenyl)methyl]indazol-3-yl]-5-methyl-6-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]ethyl]-1,2,4-oxadiazolidin-5-one | KI | 0.074 nM | US-10428076: Soluble guanylate cyclase stimulators |
| (1R,6S)-3-[6-[2-[[2-[[(2S)-1,4-dioxan-2-yl]methyl]-5-methyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 1 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[2-[[2-(1,4-dioxan-2-ylmethyl)-5,8-dimethyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 1 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3S,4S)-3-methoxy-1-[6-[3-methyl-2-[[6-methyl-3-(oxan-4-yl)-1,2,4,5-tetrahydro-3-benzazepin-8-yl]methoxy]phenyl]-2-pyridinyl]piperidine-4-carboxylic acid | EC50 | 1 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3S,4S)-3-methoxy-1-[6-[3-methyl-2-[[6-methyl-3-[(3S)-oxolan-3-yl]-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]phenyl]-2-pyridinyl]piperidine-4-carboxylic acid | EC50 | 1 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3R,4R)-1-[4-[3-chloro-2-[[(5R)-5-methyl-3-(oxan-4-yl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-methoxypiperidine-4-carboxylic acid | EC50 | 1 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3S,4S)-1-[6-[2-[[5,5-dimethyl-3-(oxetan-3-yl)-2,4-dihydro-1H-3-benzazepin-7-yl]methoxy]-3-methylphenyl]-2-pyridinyl]-3-methoxypiperidine-4-carboxylic acid | EC50 | 1 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[6-[3-methyl-2-[[8-methyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[6-[5-methyl-2-[[5-methyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,5R)-3-[6-[3-methyl-2-[[6-methyl-3-(oxetan-3-yl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[3.1.0]hexane-1-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[2-[[2-(1,4-dioxan-2-ylmethyl)-5-methyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[3-methyl-2-[[5-methyl-2-(oxan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[3-methyl-2-[[8-methyl-2-(oxolan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[3-methyl-2-[[8-methyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[3-methyl-2-[[8-methyl-2-(oxetan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[3-methyl-2-[[6-methyl-3-(oxan-4-yl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[2-[[2-(1,4-dioxan-2-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-5-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[2-[[2-(1,4-dioxan-2-ylmethyl)-5-methyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-5-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3S,4S)-3-ethoxy-1-[4-[2-[[5-fluoro-8-methyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]piperidine-4-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3R,4R)-1-[4-[2-[[5-fluoro-8-methoxy-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-methoxypiperidine-4-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3S,4S)-3-ethoxy-1-[4-[2-[[5-fluoro-8-methoxy-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]piperidine-4-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3S,4S)-3-ethoxy-1-[4-[2-[[5-fluoro-8-methoxy-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-5-methylphenyl]-1,3-thiazol-2-yl]piperidine-4-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3S,4S)-3-methoxy-1-[6-[3-methyl-2-[[6-methyl-3-(oxetan-3-yl)-1,2,4,5-tetrahydro-3-benzazepin-8-yl]methoxy]phenyl]-2-pyridinyl]piperidine-4-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[2-[[2-(4,4-difluorocyclohexyl)-8-methyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3R,4R)-1-[4-[2-[[5,5-dimethyl-3-(oxan-4-yl)-2,4-dihydro-1H-3-benzazepin-7-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-methoxypiperidine-4-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3S,4S)-1-[6-[2-[[5,5-dimethyl-3-(oxan-4-yl)-2,4-dihydro-1H-3-benzazepin-7-yl]methoxy]-3-methylphenyl]-2-pyridinyl]-3-methoxypiperidine-4-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3S,4S)-1-[4-[5-fluoro-3-methyl-2-[[(5R)-5-methyl-3-(oxan-4-yl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-methoxypiperidine-4-carboxylic acid | EC50 | 2 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[6-[2-[[5-methyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[6-[2-[[2-(1,4-dioxan-2-ylmethyl)-5-methyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[6-[3-methyl-2-[[5-methyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[2-[[2-(1,4-dioxan-2-ylmethyl)-8-methyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[3-methyl-2-[[8-methyl-2-(oxan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[2-[[5,8-dimethyl-2-(oxan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[2-[[5,8-dimethyl-2-(oxolan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[2-[[5,8-dimethyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[2-[[5,8-dimethyl-2-(oxetan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-3-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[5-methyl-2-[[5-methyl-2-(oxolan-3-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[4-[2-[[2-(1,4-dioxan-2-ylmethyl)-5,8-dimethyl-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]-5-methylphenyl]-1,3-thiazol-2-yl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3S,4S)-3-methoxy-1-[6-[3-methyl-2-[[6-methyl-3-(oxetan-3-yl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]phenyl]-2-pyridinyl]piperidine-4-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,2S,5R)-3-[6-[2-[[6-fluoro-3-(oxan-4-yl)-1,2,4,5-tetrahydro-3-benzazepin-8-yl]methoxy]-3-methylphenyl]-2-pyridinyl]-2-(methoxymethyl)-3-azabicyclo[3.1.0]hexane-1-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3R,4R)-1-[6-[3-chloro-2-[[8-methyl-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-ethoxypiperidine-4-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3R,4R)-1-[6-[3-chloro-2-[[8-methoxy-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-ethoxypiperidine-4-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3R,4R)-1-[4-[3-chloro-2-[[8-methoxy-2-(oxan-4-yl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-1,3-thiazol-2-yl]-3-ethoxypiperidine-4-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,2S,5R)-3-[6-[2-[[6-fluoro-3-(oxan-4-yl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]-3-methylphenyl]-2-pyridinyl]-2-(methoxymethyl)-3-azabicyclo[3.1.0]hexane-1-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[6-[2-[(2-cyclobutyl-5-methyl-3,4-dihydro-1H-isoquinolin-6-yl)methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (3S,4S)-3-methoxy-1-[6-[3-methyl-2-[[6-methyl-3-[(3R)-oxolan-3-yl]-1,2,4,5-tetrahydro-3-benzazepin-7-yl]methoxy]phenyl]-2-pyridinyl]piperidine-4-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[6-[2-[[5-methyl-2-(1-pyridin-2-ylethyl)-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
| (1R,6S)-3-[6-[2-[[5-methyl-2-[(5-methyl-1,2-oxazol-3-yl)methyl]-3,4-dihydro-1H-isoquinolin-6-yl]methoxy]phenyl]-2-pyridinyl]-3-azabicyclo[4.1.0]heptane-6-carboxylic acid | EC50 | 3 nM | US-9353090: Heterocyclic carboxylic acids as activators of soluble guanylate cyclase |
ChEMBL bioactivities
909 potent at pChembl≥5 of 962 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 10.66 | Ki | 0.022 | nM | CHEMBL5814188 |
| 10.59 | Ki | 0.026 | nM | CHEMBL5961042 |
| 10.54 | Ki | 0.029 | nM | CHEMBL5937094 |
| 10.51 | Ki | 0.031 | nM | CHEMBL5962881 |
| 10.51 | Ki | 0.031 | nM | CHEMBL5896066 |
| 10.51 | Ki | 0.031 | nM | CHEMBL5828124 |
| 10.41 | Ki | 0.039 | nM | CHEMBL5754765 |
| 10.39 | Ki | 0.041 | nM | CHEMBL6025572 |
| 10.38 | Ki | 0.042 | nM | CHEMBL5943807 |
| 10.35 | Ki | 0.045 | nM | CHEMBL5924970 |
| 10.33 | Ki | 0.047 | nM | CHEMBL5980517 |
| 10.32 | Ki | 0.048 | nM | CHEMBL5989618 |
| 10.31 | Ki | 0.049 | nM | CHEMBL6038148 |
| 10.30 | Ki | 0.05 | nM | CHEMBL5915567 |
| 10.28 | Ki | 0.052 | nM | CHEMBL6021981 |
| 10.28 | Ki | 0.052 | nM | CHEMBL6053909 |
| 10.25 | Ki | 0.056 | nM | CHEMBL5838947 |
| 10.24 | Ki | 0.058 | nM | CHEMBL5925728 |
| 10.24 | Ki | 0.057 | nM | CHEMBL6031103 |
| 10.24 | Ki | 0.058 | nM | CHEMBL6006393 |
| 10.24 | Ki | 0.057 | nM | CHEMBL5959396 |
| 10.24 | Ki | 0.058 | nM | CHEMBL5981554 |
| 10.22 | Ki | 0.06 | nM | CHEMBL5872155 |
| 10.21 | Ki | 0.062 | nM | CHEMBL6055856 |
| 10.21 | Ki | 0.062 | nM | CHEMBL6011397 |
| 10.21 | Ki | 0.062 | nM | CHEMBL5946879 |
| 10.20 | Ki | 0.063 | nM | CHEMBL5973404 |
| 10.20 | Ki | 0.063 | nM | CHEMBL6050464 |
| 10.19 | Ki | 0.064 | nM | CHEMBL5941930 |
| 10.18 | Ki | 0.066 | nM | CHEMBL5850021 |
| 10.18 | Ki | 0.066 | nM | CHEMBL5754222 |
| 10.17 | Ki | 0.067 | nM | CHEMBL5758630 |
| 10.17 | Ki | 0.067 | nM | CHEMBL5842014 |
| 10.17 | Ki | 0.067 | nM | CHEMBL6019970 |
| 10.17 | Ki | 0.068 | nM | CHEMBL5996734 |
| 10.17 | Ki | 0.068 | nM | CHEMBL5870392 |
| 10.15 | Ki | 0.07 | nM | CHEMBL5979143 |
| 10.15 | Ki | 0.07 | nM | CHEMBL5977775 |
| 10.14 | Ki | 0.072 | nM | CHEMBL6065117 |
| 10.14 | Ki | 0.073 | nM | CHEMBL6023523 |
| 10.13 | Ki | 0.074 | nM | CHEMBL6064339 |
| 10.13 | Ki | 0.074 | nM | CHEMBL5908747 |
| 10.13 | Ki | 0.074 | nM | CHEMBL5862357 |
| 10.12 | Ki | 0.075 | nM | CHEMBL5855606 |
| 10.12 | Ki | 0.075 | nM | CHEMBL5981113 |
| 10.12 | Ki | 0.075 | nM | CHEMBL5793164 |
| 10.12 | Ki | 0.076 | nM | CHEMBL5965599 |
| 10.11 | Ki | 0.078 | nM | CHEMBL5828379 |
| 10.11 | Ki | 0.077 | nM | CHEMBL6032838 |
| 10.10 | Ki | 0.079 | nM | CHEMBL5972747 |
PubChem BioAssay actives
72 with measured affinity, of 284 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]piperidine-4-carboxylic acid | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.0070 | uM |
| 1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]piperidin-4-ol | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.0100 | uM |
| 5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-N-methylpyrimidin-4-amine | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.0200 | uM |
| 3-[1-[(2-fluorophenyl)methyl]-3-(5-fluoro-4-piperidin-1-ylpyrimidin-2-yl)pyrazol-5-yl]-1,2-oxazole | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.0270 | uM |
| 1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]piperidin-3-ol | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.0330 | uM |
| (2R,3S)-1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]-3-methylpiperidine-2-carboxylic acid | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.0330 | uM |
| [1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]piperidin-2-yl]methanol | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.0350 | uM |
| (2S,3R)-1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]-3-methylpiperidine-2-carboxylic acid | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.0400 | uM |
| 5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-N-(2-morpholin-4-ylethyl)pyrimidin-4-amine | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.0410 | uM |
| 4-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]morpholine | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.0500 | uM |
| 1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]piperidine-3-carboxylic acid | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.0550 | uM |
| 3-[1-[(2-fluorophenyl)methyl]-3-(5-fluoro-4-pyrrolidin-1-ylpyrimidin-2-yl)pyrazol-5-yl]-1,2-oxazole | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.0830 | uM |
| 5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.0970 | uM |
| methyl N-[4,6-diamino-2-[3-[(2,3,5-trifluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate | 1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay | ec50 | 0.1100 | uM |
| 6-amino-2-[3-[(2-fluorophenyl)methyl]indazol-1-yl]-7-methyl-9H-purin-8-one | 1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay | ec50 | 0.1200 | uM |
| 3-[1-[(2-fluorophenyl)methyl]-3-(5-fluoro-4-piperazin-1-ylpyrimidin-2-yl)pyrazol-5-yl]-1,2-oxazole | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.1200 | uM |
| (2R)-1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]piperidine-2-carboxylic acid | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.1200 | uM |
| 5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-amine | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.1300 | uM |
| 6-amino-2-[5-chloro-3-[(2-fluorophenyl)methyl]indazol-1-yl]-7-methyl-9H-purin-8-one | 1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay | ec50 | 0.1400 | uM |
| 3-[3-[4-(3,3-difluoropiperidin-1-yl)-5-fluoropyrimidin-2-yl]-1-[(2-fluorophenyl)methyl]pyrazol-5-yl]-1,2-oxazole | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.1500 | uM |
| 4-amino-2-[3-[(2-fluorophenyl)methyl]indazol-1-yl]-5,7-dihydropyrrolo[2,3-d]pyrimidin-6-one | 1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay | ec50 | 0.1600 | uM |
| 5-(4-chlorophenyl)sulfonyl-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.1600 | uM |
| 5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-thiazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.1800 | uM |
| 6-amino-7-ethyl-2-[3-[(2-fluorophenyl)methyl]indazol-1-yl]-9H-purin-8-one | 1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay | ec50 | 0.2000 | uM |
| (2S)-1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]piperidine-2-carboxylic acid | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.2000 | uM |
| 2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-amine | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.2400 | uM |
| 5-fluoro-2-[1-[(2-fluoro-3-methylphenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.2400 | uM |
| 4-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]-1,4-thiazinane 1,1-dioxide | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.2400 | uM |
| 3-[3-[4-(4,4-difluoropiperidin-1-yl)-5-fluoropyrimidin-2-yl]-1-[(2-fluorophenyl)methyl]pyrazol-5-yl]-1,2-oxazole | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.2500 | uM |
| methyl N-[4,6-diamino-2-[3-[(2,5-difluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate | 1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay | ec50 | 0.2700 | uM |
| methyl N-[4,6-diamino-2-[3-[(2,3,6-trifluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate | 1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay | ec50 | 0.2700 | uM |
| 5-fluoro-2-[1-[(3-fluorothiophen-2-yl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.2800 | uM |
| methyl N-[4,6-diamino-2-[3-[(2,3-difluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate | 1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay | ec50 | 0.3000 | uM |
| 6-amino-2-[3-[(2-fluorophenyl)methyl]indazol-1-yl]-7,9-dihydropurin-8-one | 1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay | ec50 | 0.3000 | uM |
| methyl N-[4,6-diamino-2-[3-[(2-fluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate | 1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay | ec50 | 0.3100 | uM |
| 3-[3-(5-fluoro-4-methoxypyrimidin-2-yl)-1-[(2-fluorophenyl)methyl]pyrazol-5-yl]-1,2-oxazole | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.3200 | uM |
| methyl N-[4,6-diamino-2-[5-chloro-3-[(2-fluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate | 1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay | ec50 | 0.3500 | uM |
| 5-(benzenesulfonyl)-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.3500 | uM |
| 2-[1-[(2,3-difluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-5-fluoro-1H-pyrimidin-6-one | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.3700 | uM |
| 2-[1-[(3-chloro-2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-5-fluoro-1H-pyrimidin-6-one | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.3800 | uM |
| 2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-6-oxo-1H-pyrimidine-5-carbonitrile | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.5000 | uM |
| 2-[1-[(2,4-difluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-5-fluoro-1H-pyrimidin-6-one | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.5300 | uM |
| 5-chloro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-1H-pyrimidin-6-one | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.5900 | uM |
| methyl N-[4,6-diamino-2-[5-chloro-3-[(2,3,6-trifluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]carbamate | 1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay | ec50 | 0.6700 | uM |
| methyl N-[4,6-diamino-2-[5-chloro-3-[(2,3,6-trifluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate | 1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay | ec50 | 0.7000 | uM |
| 2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-N-methyl-6-oxo-N-phenyl-1H-pyrimidine-5-sulfonamide | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.7300 | uM |
| 2-[1-benzyl-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-5-fluoro-1H-pyrimidin-6-one | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.8800 | uM |
| 2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]-5-methylsulfonyl-1H-pyrimidin-6-one | 1304082: Activation of SGC in HEK293 cells assessed as cGMP production after 20 mins by LC-MS/MS analysis in presence of NO-donor DETA-NONOate | ec50 | 0.9000 | uM |
| methyl N-[4,6-diamino-2-[5-fluoro-3-[(2-fluorophenyl)methyl]indazol-1-yl]pyrimidin-5-yl]-N-methylcarbamate | 1677320: Activation of human sGC subunit alpha1/beta1 expressed in CHO cells assessed as cGMP production by CASA assay | ec50 | 0.9600 | uM |
| (2S)-1-[5-fluoro-2-[1-[(2-fluorophenyl)methyl]-5-(1,2-oxazol-3-yl)pyrazol-3-yl]pyrimidin-4-yl]pyrrolidine-2-carboxylic acid | 1757088: Activation of sGC (unknown origin) in presence of DETA-NO by Glosensor cGMP assay | ec50 | 0.9700 | uM |
CTD chemical–gene interactions
65 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Valproic Acid | affects expression, increases expression, increases methylation | 7 |
| bisphenol A | decreases expression, increases expression | 3 |
| 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one | increases activity, increases reaction, affects cotreatment, affects binding, affects folding (+1 more) | 2 |
| entinostat | affects cotreatment, decreases expression | 2 |
| ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate | affects cotreatment, affects expression | 1 |
| fluorene-9-bisphenol | increases expression | 1 |
| methylmercuric chloride | decreases expression | 1 |
| triphenyl phosphate | affects expression | 1 |
| propionaldehyde | increases expression | 1 |
| trichostatin A | increases expression | 1 |
| sodium arsenite | increases expression | 1 |
| butyraldehyde | increases expression | 1 |
| perfluorooctanoic acid | affects expression, affects cotreatment | 1 |
| protoporphyrin IX | increases activity, increases reaction, affects binding | 1 |
| potassium ferricyanide | affects binding, decreases reaction, increases activity | 1 |
| hydroquinone | increases expression | 1 |
| S-(1,2-dichlorovinyl)cysteine | decreases reaction, increases expression | 1 |
| pentanal | increases expression | 1 |
| perfluorooctane sulfonic acid | affects expression, affects cotreatment | 1 |
| 1,1-diethyl-2-hydroxy-2-nitrosohydrazine | affects binding, increases activity, decreases reaction | 1 |
| 3-(5’-hydroxymethyl-2’-furyl)-1-benzylindazole | affects binding, affects folding | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| 3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine | affects binding, increases activity, increases reaction | 1 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | decreases expression, affects cotreatment | 1 |
| BAY 58-2667 | affects binding, affects cotreatment, increases activity, increases reaction | 1 |
| 2,2’,4,4’-tetrabromodiphenyl ether | decreases expression | 1 |
| dicyanocobinamide | affects binding, increases activity, increases reaction, decreases reaction, increases metabolic processing | 1 |
| 5-chloro-2-(5-chlorothiophene-2-sulfonylamino)-N-(4-(morpholine-4-sulfonyl)phenyl)benzamide | affects binding, increases activity, increases reaction | 1 |
| dorsomorphin | affects cotreatment, decreases expression | 1 |
| hexabrominated diphenyl ether 153 | decreases expression | 1 |
ChEMBL screening assays
45 unique, capped per target: 40 binding, 5 functional
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1918701 | Binding | Activation of human soluble guanylate cyclase assessed as production of cGMP in presence of nitric oxide donor, SIN-1 by LC-MS enzyme assay | Acidic triazoles as soluble guanylate cyclase stimulators. — Bioorg Med Chem Lett |
| CHEMBL865676 | Functional | Effect on cGMP production in porcine iris-ciliary body at 10 uM | Synthesis and ocular effects of imidazole nitrolic acid and amidoxime esters. — Bioorg Med Chem Lett |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): diabetic retinopathy