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cyclic GMP-AMP synthase

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 3165

Nomenclature: cyclic GMP-AMP synthase

Family: Cyclic GMP-AMP turnover

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 522 6q13 CGAS cyclic GMP-AMP synthase
Mouse - 507 9 E1 Cgas cyclic GMP-AMP synthase
Rat - 358 8q31 Cgas cyclic GMP-AMP synthase
Database Links Click here for help
Alphafold Q8N884 (Hs), Q8C6L5 (Mm)
BRENDA 2.7.7.86
ChEMBL Target CHEMBL4105728 (Hs), CHEMBL4523383 (Mm)
Ensembl Gene ENSG00000164430 (Hs), ENSMUSG00000032344 (Mm), ENSRNOG00000046191 (Rn)
Entrez Gene 115004 (Hs), 214763 (Mm), 682147 (Rn)
Human Protein Atlas ENSG00000164430 (Hs)
KEGG Enzyme 2.7.7.86
KEGG Gene hsa:115004 (Hs), mmu:214763 (Mm), rno:682147 (Rn)
OMIM 613973 (Hs)
Pharos Q8N884 (Hs)
RefSeq Nucleotide NM_138441 (Hs), NM_173386 (Mm)
RefSeq Protein NP_612450 (Hs), NP_775562 (Mm)
UniProtKB Q8N884 (Hs), Q8C6L5 (Mm)
Wikipedia CGAS (Hs)
Enzyme Reaction Click here for help
EC Number: 2.7.7.86 ATP + GTP <=> 2 diphosphate + cyclic G-P(2'-5')A-P(3'-5')

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
PF‐06928215 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 6.7 pKd 1
⤷ pKd 6.7 (Kd 2x10-7 M) [1]
Description: Binding affinity determined by SPR.
compound 20 [PMID: 37666112] Small molecule or natural product Ligand has a PDB structure Mm Inhibition 5.8 pIC50 3
⤷ pIC50 5.8 (IC50 1.44x10-6 M) [3]
compound 20 [PMID: 37666112] Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.6 pIC50 3
⤷ pIC50 5.6 (IC50 2.28x10-6 M) [3]
baicalin Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.4 pIC50 3
⤷ pIC50 5.4 (IC50 3.97x10-6 M) [3]
PF‐06928215 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 5.3 pIC50 1
⤷ pIC50 5.3 (IC50 4.9x10-6 M) [1]
Description: Enzyme inhibition determined by FP assay.
baicalin Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Mm Inhibition 5.0 pIC50 3
⤷ pIC50 5.0 (IC50 1.084x10-5 M) [3]
View species-specific inhibitor tables
Immunopharmacology Comments
Cyclic GMP-AMP synthase (cGAS) directly binds to cytosolic DNA, and in response catalyses the synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Thus cGAS acts as a sensor of DNA in the cytoplasm, which is an indicator of pathogen invasion [4]. The generated cGAMP then binds to STING (stimulator of interferon genes) which is a key mediator of the innate immune system, whose activation induces production of interferons and inflammatory cytokines (via IRF3‐ and NF-κB‐dependent transcription). The cGAS-STING pathway is also associated with a number of human sterile inflammatory conditions and cancer. Pharmacological modulation of both cGAS [2] and STING is being explored for clinical potential. cGAS‐specific small molecule inhibitor development has primarily identified compounds that occupy the enzyme's active site.
Immuno Process Associations
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 5 GO processes, IEA only
GO:0002221 pattern recognition receptor signaling pathway IDA
GO:0002753 cytoplasmic pattern recognition receptor signaling pathway IDA
GO:0140896 cGAS/STING signaling pathway IDA
GO:0160049 negative regulation of cGAS/STING signaling pathway IDA
click arrow to show/hide IEA associations
GO:0050863 regulation of T cell activation IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 4 GO processes
GO:0002753 cytoplasmic pattern recognition receptor signaling pathway IDA
GO:0032481 positive regulation of type I interferon production IDA
GO:0140896 cGAS/STING signaling pathway IDA
GO:0160049 negative regulation of cGAS/STING signaling pathway IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 7 GO processes, IEA only
GO:0002218 activation of innate immune response IDA
GO:0002221 pattern recognition receptor signaling pathway IDA
GO:0002753 cytoplasmic pattern recognition receptor signaling pathway IDA
GO:0140896 cGAS/STING signaling pathway IDA
GO:0160049 negative regulation of cGAS/STING signaling pathway IDA
click arrow to show/hide IEA associations
GO:0002637 regulation of immunoglobulin production IEA
GO:0050863 regulation of T cell activation IEA
Immuno Process:  Inflammation
GO Annotations:  Associated to 6 GO processes
GO:0002218 activation of innate immune response IDA
GO:0002221 pattern recognition receptor signaling pathway IDA
GO:0002753 cytoplasmic pattern recognition receptor signaling pathway IDA
GO:0045087 innate immune response TAS
GO:0140896 cGAS/STING signaling pathway IDA
GO:0160049 negative regulation of cGAS/STING signaling pathway IDA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0050863 regulation of T cell activation IEA

References

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1. Hall J, Brault A, Vincent F, Weng S, Wang H, Dumlao D, Aulabaugh A, Aivazian D, Castro D, Chen M et al.. (2017) Discovery of PF-06928215 as a high affinity inhibitor of cGAS enabled by a novel fluorescence polarization assay. PLoS One, 12 (9): e0184843. [PMID:28934246]

2. Hertzog J, Rehwinkel J. (2020) Regulation and inhibition of the DNA sensor cGAS. EMBO Rep, 21 (12): e51345. [PMID:33155371]

3. Li J, Xiong M, Liu J, Zhang F, Li M, Zhao W, Xu Y. (2023) Discovery of novel cGAS inhibitors based on natural flavonoids. Bioorg Chem, 140: 106802. [PMID:37666112]

4. Sun L, Wu J, Du F, Chen X, Chen ZJ. (2013) Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science, 339 (6121): 786-91. [PMID:23258413]

How to cite this page

Cyclic GMP-AMP turnover: cyclic GMP-AMP synthase. Last modified on 03/06/2025. Accessed on 03/07/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3165.