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STING Agonist Library

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ChemDiv’s library of small molecule agonists of the Stimulator of interferon genes (STING) contains 5,939 compounds.

Stimulator of interferon genes (STING), which is also known as transmembrane protein 173 (TMEM173), as well as by its other designations MPYS, MITA, and ERIS, constitutes a protein encoded in humans by the TMEM173 gene. STING is a crucial component in the human immune system, with a significant role in the defense against pathogens and in the development of certain diseases.

STING is integral to the innate immune response, the body's first line of defense against pathogens. It is involved in detecting foreign DNA inside the cells, particularly from viruses, bacteria, or even mislocated self-DNA. This detection is often mediated through the cyclic GMP-AMP synthase (cGAS), which produces cyclic GMP-AMP (cGAMP) upon encountering cytosolic DNA. cGAMP then binds to STING, activating it. Once activated, STING initiates a signaling cascade that leads to the production of type I interferons and other inflammatory cytokines. These are crucial for initiating an antiviral state in the cells and alerting the immune system to the presence of pathogens. This pathway involves the phosphorylation and activation of various intermediary proteins and transcription factors like IRF3 and NF-kB.

Dysregulation of the STING pathway can contribute to a variety of diseases. Overactivation can lead to chronic inflammation and autoimmune diseases, where the body's immune system mistakenly attacks its own cells. Conversely, under activation or defects in the STING pathway can lead to increased susceptibility to viral infections and potentially contribute to certain types of cancer due to impaired immune surveillance. Given its pivotal role in the immune response, STING is an attractive target for drug development.

STING agonists can boost the immune system's ability to fight against viruses and cancer. By activating STING, these drugs can enhance the body’s antiviral responses and possibly improve the efficacy of cancer immunotherapies.

In conditions where the STING pathway is overactive, such as in autoimmune diseases, STING antagonists may help to reduce inflammation and mitigate tissue damage.

Targeting STING in therapy holds considerable potential, but it also presents challenges. Precise modulation of STING activity is crucial; overstimulation can lead to harmful inflammation, while inadequate activation might not provide the desired therapeutic effect. Therefore, the development of STING-targeted therapies requires a careful balance to achieve optimal outcomes.

Our library of STING agonists offers significant benefits for drug discovery, notably in speeding up the process by providing a range of molecules for immediate screening. This collection facilitates the development of targeted therapies, particularly for cancer immunotherapy and viral infections, by enabling a deeper understanding of the STING pathway's activation and signaling mechanisms. It aids in identifying potent agonists for effective immune response stimulation while also allowing for the development of combination therapies and personalized medicine approaches. Additionally, by comparing different agonists, researchers can minimize adverse side effects, enhancing the safety of potential treatments. This library also contributes to research in autoimmune diseases, providing insights into the regulation of STING activity.

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