1441190-66-4 Usage
Description
2'3'-cGAMP, also known as 2'3'-cyclic GMP-AMP, is an endogenous stimulator of interferon genes (STING) agonist derived from ATP and GTP through the action of cGMP-AMP synthase (cGAS), which acts as a cytosolic DNA sensor. It plays a crucial role in the immune response by inducing autophagy for the clearance of DNA and viruses in the cytosol and stimulating an inflammatory response upon DNA damage.
Uses
Used in Research Applications:
2'3'-cGAMP is used as a research tool for identifying small compounds capable of binding to human stimulator of interferon genes (STING). This application aids in understanding the type I interferon response to cytosolic DNA and contributes to the development of potential therapeutic strategies targeting STING pathways.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 2'3'-cGAMP is used as a drug candidate for modulating the immune response, particularly in the context of viral infections and cancer. Its ability to stimulate an inflammatory response and induce autophagy makes it a promising candidate for the development of novel therapeutics targeting various diseases.
Used in Diagnostic Applications:
2'3'-cGAMP can be employed in the development of diagnostic tools to detect and monitor the presence of cytosolic DNA and viruses, as well as assess the functionality of the STING pathway in various disease conditions.
Biochem/physiol Actions
2′,3′-cGAMP (cyclic [G(2′,5′)pA(3′,5′)p]) is the natural agonist for the STING (STimulator of INterferon Genes) pathway, discovered to be a pathway for antiviral innate immunity. 2′3′-cGAMP is a second messenger produced in mammalian cells by the cytosolic DNA sensor cGAS (cGAMP synthase) to activate innate immune responses by binding to STING and initiating an interferon response. The affinity of 2′3′-cGAMP for human STING is much higher than that of the bacterial 3′3′-cyclic dinucleotides (CDNs), with a Kd of 4.59 nM compared to >1 μM for bacterial 3′3′-CDNs.
References
1) Zhang?et al.?(2015), Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING; Mol. Cell?51?226
2) Wu?et al.?(2013), Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA; Science?339?826
3) Sun?et al.?(2013), Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway; Science?339?786
4) Gui?et al.?(2019),?Autophagy induction via STING trafficking is a primordial function of the cGAS pathway;??Nature,?567?262
5) Li and Chen (2018),?The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence and cancer;??J. Exp. Med.,?215?1287
Check Digit Verification of cas no
The CAS Registry Mumber 1441190-66-4 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,4,1,1,9 and 0 respectively; the second part has 2 digits, 6 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 1441190-66:
(9*1)+(8*4)+(7*4)+(6*1)+(5*1)+(4*9)+(3*0)+(2*6)+(1*6)=134
134 % 10 = 4
So 1441190-66-4 is a valid CAS Registry Number.
1441190-66-4Relevant articles and documents
The catalytic mechanism of cyclic GMP-AMP synthase (cGAS) and implications for innate immunity and inhibition
Hall, Justin,Ralph, Erik C.,Shanker, Suman,Wang, Hong,Byrnes, Laura J.,Horst, Reto,Wong, Jimson,Brault, Amy,Dumlao, Darren,Smith, James F.,Dakin, Leslie A.,Schmitt, Daniel C.,Trujillo, John,Vincent, Fabien,Griffor, Matt,Aulabaugh, Ann E.
, p. 2367 - 2380 (2017)
Cyclic GMP-AMP synthase (cGAS) is activated by ds-DNA binding to produce the secondary messenger 2′,3′-cGAMP. cGAS is an important control point in the innate immune response; dysregulation of the cGAS pathway is linked to autoimmune diseases while targeted stimulation may be of benefit in immunoncology. We report here the structure of cGAS with dinucleotides and small molecule inhibitors, and kinetic studies of the cGAS mechanism. Our structural work supports the understanding of how ds-DNA activates cGAS, suggesting a site for small molecule binders that may cause cGAS activation at physiological ATP concentrations, and an apparent hotspot for inhibitor binding. Mechanistic studies of cGAS provide the first kinetic constants for 2′,3′-cGAMP formation, and interestingly, describe a catalytic mechanism where 2′,3′-cGAMP may be a minor product of cGAS compared with linear nucleotides.
