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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
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Bioactive modulators targeting STING adaptor in cGAS-STING pathway.

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The cyclic GMP-AMP synthase (cGAS)-STING pathway detects DNA to initiate immune responses. New STING modulators show therapeutic promise for various diseases, including cancer.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Drug Discovery

Background:

  • The cGAS-STING pathway is crucial for innate immunity, sensing cytosolic DNA to trigger immune responses.
  • Dysregulation of the STING pathway is linked to various diseases, highlighting its therapeutic relevance.
  • Recent advancements include the identification of STING modulators, with several agonists entering clinical trials for cancer treatment.

Purpose of the Study:

  • To summarize recent progress in understanding STING pathway functioning.
  • To provide an overview of newly discovered STING modulators.
  • To discuss the therapeutic potential of STING modulators.

Main Methods:

  • Literature review of recent studies on the cGAS-STING pathway.
  • Analysis of identified STING agonists and antagonists.
  • Examination of structural details and therapeutic applications of STING modulators.

Main Results:

  • The cGAS-STING pathway's role in innate immunity and disease association is further elucidated.
  • Several novel STING modulators, including agonists and antagonists, have been discovered.
  • Structural insights into STING modulators are providing a basis for therapeutic development.

Conclusions:

  • The STING pathway represents a promising therapeutic target for a range of diseases.
  • STING agonists and antagonists are advancing towards clinical application, particularly in oncology.
  • Continued research into STING modulators may yield novel treatments for immune-related disorders.