Related Experiment Video
Updated: Nov 20, 2025
06:19
Author Spotlight: Exploring the Role of Ion Channels in Cancer: Characterization and Potential Treatment Approaches
Published on: June 16, 2023
3.6K
Advances in Targeting GIRK Channels in Disease
Yulin Zhao1, Isabel Gameiro-Ros1, Ian W Glaaser1
1Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Trends in Pharmacological Sciences
|January 20, 2021
Summary
New small molecules specifically target G protein-gated inwardly rectifying potassium (GIRK) channels, offering untapped therapeutic potential for neurological diseases by precisely regulating neuronal excitability.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- G protein-gated inwardly rectifying potassium (GIRK) channels are crucial for regulating neuronal excitability in the brain.
- Dysfunction of GIRK channels is linked to various neurological disorders, yet their therapeutic applications remain underdeveloped.
Purpose of the Study:
- To review recent advancements in small molecule modulators targeting GIRK channels.
- To compare novel selective compounds with older, less specific agents.
- To highlight the potential for targeted neurological therapies.
Main Methods:
- Review of literature on small molecule discovery for GIRK channels.
- Analysis of chemical properties and in vivo effects of identified modulators.
- Comparison of selectivity and off-target activities of different compound generations.
Main Results:
- Development of novel small molecules with high specificity for GIRK channels.
- Demonstration of in vivo efficacy of these selective modulators.
- Identification of distinct chemical features correlating with improved target engagement.
Conclusions:
- Emerging subunit-specific GIRK modulators offer a promising avenue for treating neurological conditions.
- Targeted modulation of neuronal excitability in a brain region-specific manner is achievable.
- These findings pave the way for developing novel therapeutics with improved safety and efficacy profiles.
Related Concept Videos
02:57Targeted Cancer Therapies
8.1K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
8.1K
01:26Targets for Drug Action: Overview
9.0K
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
9.0K
01:27Transducer Mechanism: Enzyme-Linked Receptors
3.5K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
3.5K
01:15G Protein-coupled Receptors
15.2K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
15.2K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.4K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
3.4K
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
317
Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
317