Top ▲
Gene and Protein Information ![]() |
||||||
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 ![]() |
|
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 ![]() |
||||
|
Download all structure-activity data for this target as a CSV file
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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. |
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]
Cyclic GMP-AMP synthase: Cyclic GMP-AMP synthase. Last modified on 08/01/2024. Accessed on 14/02/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3165.