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Related Concept Videos

Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:29

Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship

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Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
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Drug-Receptor Interaction: Agonist01:25

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Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
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Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:22

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Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
The direct-acting...
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Adrenergic Agonists: Direct-Acting Agents01:30

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Drugs that mimic the action of endogenous catecholamines like noradrenaline and adrenaline are called adrenergic agonists or sympathomimetics. Based on their mechanism of action, sympathomimetics can be classified as direct-, indirect-, or mixed-acting sympathomimetics. Direct-acting adrenergic agonists activate adrenoceptors without affecting presynaptic neurons, making them independent of neuronal catecholamine-depleting agents like reserpine and guanethidine.
These agents can be classified...
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Cholinergic Antagonists: Chemistry and Structure-Activity Relationship01:29

Cholinergic Antagonists: Chemistry and Structure-Activity Relationship

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Cholinergic antagonists bind to cholinergic receptors and limit the effects of acetylcholine and other cholinergic agonists. Based on the specific cholinergic receptor affinity, these antagonists are classified as muscarinic or nicotinic. Anticholinergics interrupt parasympathetic innervations while sympathetic innervations remain uninterrupted. Muscarinic antagonists are also called 'muscarinic antagonists', 'antimuscarinics', or 'parasympatholytics'. Nicotinic...
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Direct-Acting Cholinergic Agonists: Therapeutic Uses01:11

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Direct-acting cholinergic agonists have many therapeutic uses in various medical fields. Choline esters, including acetylcholine, have limited clinical utility due to their non-selectivity and short duration of action. Still, acetylcholine and carbachol are applied topically during ophthalmologic surgery to induce miosis. Pilocarpine, a muscarinic and ganglionic stimulator, effectively treats open-angle glaucoma and alleviates xerostomia and dry mouth caused by radiotherapy or Sjögren...
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Updated: May 10, 2025

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Conjugated STING agonists.

Shuhao Qu1, Hong Dai2

  • 1School of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou 450046, China.

Molecular Therapy. Nucleic Acids
|April 28, 2025
PubMed
Summary
This summary is machine-generated.

Stimulator of interferon genes (STING) agonists are crucial for innate immunity. This review explores novel non-cyclic dinucleotide (CDN) STING agonists and conjugation delivery strategies for enhanced cancer immunotherapy, addressing CDN limitations.

Keywords:
CDNsMT: Delivery StrategiesSTINGSTING agonistsclinical trialsconjugatedstimulator of interferon genes

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Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • The innate immune system provides the first line of defense against pathogens.
  • Stimulator of interferon genes (STING) is a key regulator of innate immunity, crucial for initiating immune responses.
  • STING activation triggers downstream signaling pathways, leading to the production of type I interferons and inflammatory cytokines, which enhance adaptive immunity and T cell activation.

Purpose of the Study:

  • To review the development of novel Stimulator of interferon genes (STING) agonists, focusing on non-cyclic dinucleotide (CDN) alternatives.
  • To examine the efficacy of conjugation strategies for delivering STING agonists, particularly in the context of cancer immunotherapy.
  • To discuss the current challenges and future potential of STING agonists in clinical applications for cancer treatment.

Main Methods:

  • Literature review of recent advancements in STING agonist development and delivery systems.
  • Analysis of chemical modifications and non-CDN STING agonist designs.
  • Evaluation of conjugation strategies, including liposomes and nanoparticles, for STING agonist delivery.
  • Focus on STING agonists currently in clinical trials for cancer immunotherapy.

Main Results:

  • Cyclic dinucleotides (CDNs), natural STING agonists, face challenges including poor stability, high polarity, systemic toxicity, and limited clinical efficacy.
  • Significant efforts have been directed towards developing chemically modified CDNs and novel non-CDN STING agonists.
  • Conjugation strategies and nanosystem-based delivery show promise in overcoming the limitations of traditional CDNs.
  • Several STING agonists are progressing through clinical trials, indicating therapeutic potential.

Conclusions:

  • Novel STING agonists and advanced delivery systems are critical for overcoming the limitations of CDNs in cancer immunotherapy.
  • Conjugation strategies offer a promising approach to enhance the stability, targeting, and efficacy of STING agonists.
  • Further research and clinical evaluation are necessary to fully realize the potential of STING agonists in treating cancer.